bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Octenyl Succinic Anhydride (OSA) Modified Starches on the Rheological Properties of Dough and Characteristic of the Gluten-Free Bread
Authors: Korus Jarosław , Ziobro Rafał , Witczak Teresa , Kapusniak (Jochym) Kamila , Juszczak Lesław
Published: April 2021

The study focused on the influence of starch modified by octenyl succinic anhydride (OSA) on the rheological and thermal properties of gluten-free dough containing corn and potato starch with the addition of pectin and guar gum as structure-forming substances. The starch blend used in the original dough recipe was partially (5% to 15%) replaced with OSA starch. The rheological properties of dough samples were determined, and the properties of the resulting bread were analyzed. It was found that the dough samples behaved as weak gels, and the values of storage and loss moduli (G′ and G″, respectively) significantly depended on angular frequency. Various shares of OSA starch in recipes modified dough in different ways, causing changes in its rheological characteristics. The introduction of OSA starch preparations resulted in changes in the bread volume and physical characteristics of the crumb. All the applied preparations caused an increase in bread porosity and the number of pores larger than 5 mm, and there was a parallel decrease in pore density. The presence of OSA starch preparations modified bread texture depending on the amount and type of the applied preparation. The introduction of OSA starches in gluten-free bread formulation caused a significant drop in the enthalpy of retrograded amylopectin decomposition, indicating a beneficial influence of such type of additive on staling retardation in gluten-free bread.
Exploring Effects of Chitosan Oligosaccharides on the DSS-Induced Intestinal Barrier Impairment In Vitro and In Vivo
Authors: Wang Yujie , Wen Rong , Liu Dongdong , Zhang Chen , Wang Zhuo A. , Du Yuguang
Published: April 2021

Intestinal barrier dysfunction is an essential pathological change in inflammatory bowel disease (IBD). The mucus layer and the intestinal epithelial tight junction act together to maintain barrier integrity. Studies showed that chitosan oligosaccharide (COS) had a positive effect on gut health, effectively protecting the intestinal barrier in IBD. However, these studies usually focused on its impact on the intestinal epithelial tight junction. The influence of COS on the intestinal mucus layer is still poorly understood. In this study, we explored the effect of COS on intestinal mucus in vitro using human colonic mucus-secreted HT-29 cells. COS relieved DSS (dextran sulfate sodium)-induced mucus defects. Additionally, the structural characteristics of COS greatly influenced this activity. Finally, we evaluated the protective effect of COS on intestinal barrier function in mice with DSS-induced colitis. The results indicated that COS could manipulate intestinal mucus production, which likely contributed to its intestinal protective effects.
Multiplexed In Situ Protein Profiling with High-Performance Cleavable Fluorescent Tyramide
Authors: Pham Thai , Liao Renjie , Labaer Joshua , Guo Jia
Published: April 2021

Understanding the composition, function and regulation of complex cellular systems requires tools that quantify the expression of multiple proteins at their native cellular context. Here, we report a highly sensitive and accurate protein in situ profiling approach using off-the-shelf antibodies and cleavable fluorescent tyramide (CFT). In each cycle of this method, protein targets are stained with horseradish peroxidase (HRP) conjugated antibodies and CFT. Subsequently, the fluorophores are efficiently cleaved by mild chemical reagents, which simultaneously deactivate HRP. Through reiterative cycles of protein staining, fluorescence imaging, fluorophore cleavage, and HRP deactivation, multiplexed protein quantification in single cells in situ can be achieved. We designed and synthesized the high-performance CFT, and demonstrated that over 95% of the staining signals can be erased by mild chemical reagents while preserving the integrity of the epitopes on protein targets. Applying this method, we explored the protein expression heterogeneity and correlation in a group of genetically identical cells. With the high signal removal efficiency, this approach also enables us to accurately profile proteins in formalin-fixed paraffin-embedded (FFPE) tissues in the order of low to high and also high to low expression levels.
Catalytic Conversion of Xylose to Furfural by p-Toluenesulfonic Acid (pTSA) and Chlorides: Process Optimization and Kinetic Modeling
Authors: Sajid Muhammad , Rizwan Dilshad Muhammad , Saif Ur Rehman Muhammad , Liu Dehua , Zhao Xuebing
Published: April 2021

Furfural is one of the most promising precursor chemicals with an extended range of downstream derivatives. In this work, conversion of xylose to produce furfural was performed by employing p-toluenesulfonic acid (pTSA) as a catalyst in DMSO medium at moderate temperature and atmospheric pressure. The production process was optimized based on kinetic modeling of xylose conversion to furfural alongwith simultaneous formation of humin from xylose and furfural. The synergetic effects of organic acids and Lewis acids were investigated. Results showed that the catalyst pTSA-CrCl3·6H2O was a promising combined catalyst due to the high furfural yield (53.10%) at a moderate temperature of 120 °C. Observed kinetic modeling illustrated that the condensation of furfural in the DMSO solvent medium actually could be neglected. The established model was found to be satisfactory and could be well applied for process simulation and optimization with adequate accuracy. The estimated values of activation energies for xylose dehydration, condensation of xylose, and furfural to humin were 81.80, 66.50, and 93.02 kJ/mol, respectively.
Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19
Authors: Daood Umer , Gopinath Divya , Pichika Malikarjuna Rao , Mak Kit-Kay , Seow Liang Lin
Published: April 2021

To determine whether quaternary ammonium (k21) binds to Severe Acute Respiratory Syndrome–Coronavirus 2 (SARS-CoV-2) spike protein via computational molecular docking simulations, the crystal structure of the SARS-CoV-2 spike receptor-binding domain complexed with ACE-2 (PDB ID: 6LZG) was downloaded from RCSB PD and prepared using Schrodinger 2019-4. The entry of SARS-CoV-2 inside humans is through lung tissues with a pH of 7.38–7.42. A two-dimensional structure of k-21 was drawn using the 2D-sketcher of Maestro 12.2 and trimmed of C18 alkyl chains from all four arms with the assumption that the core moiety k-21 was without C18. The immunogenic potential of k21/QA was conducted using the C-ImmSim server for a position-specific scoring matrix analyzing the human host immune system response. Therapeutic probability was shown using prediction models with negative and positive control drugs. Negative scores show that the binding of a quaternary ammonium compound with the spike protein’s binding site is favorable. The drug molecule has a large Root Mean Square Deviation fluctuation due to the less complex geometry of the drug molecule, which is suggestive of a profound impact on the regular geometry of a viral protein. There is high concentration of Immunoglobulin M/Immunoglobulin G, which is concomitant of virus reduction. The proposed drug formulation based on quaternary ammonium to characterize affinity to the SARS-CoV-2 spike protein using simulation and computational immunological methods has shown promising findings.
Snake Venom Components: Tools and Cures to Target Cardiovascular Diseases
Authors: Frangieh Jacinthe , Rima Mohamad , Fajloun Ziad , Henrion Daniel , Sabatier Jean-Marc , Legros Christian , Mattei César
Published: April 2021

Cardiovascular diseases (CVDs) are considered as a major cause of death worldwide. Therefore, identifying and developing therapeutic strategies to treat and reduce the prevalence of CVDs is a major medical challenge. Several drugs used for the treatment of CVDs, such as captopril, emerged from natural products, namely snake venoms. These venoms are complex mixtures of bioactive molecules, which, among other physiological networks, target the cardiovascular system, leading to them being considered in the development and design of new drugs. In this review, we describe some snake venom molecules targeting the cardiovascular system such as phospholipase A2 (PLA2), natriuretic peptides (NPs), bradykinin-potentiating peptides (BPPs), cysteine-rich secretory proteins (CRISPs), disintegrins, fibrinolytic enzymes, and three-finger toxins (3FTXs). In addition, their molecular targets, and mechanisms of action—vasorelaxation, inhibition of platelet aggregation, cardioprotective activities—are discussed. The dissection of their biological effects at the molecular scale give insights for the development of future snake venom-derived drugs.
Investigate on the Mechanism of HfO2/Si0.7Ge0.3 Interface Passivation Based on Low-Temperature Ozone Oxidation and Si-Cap Methods
Authors: Yao Qide , Ma Xueli , Wang Hanxiang , Wang Yanrong , Wang Guilei , Zhang Jing , Liu Wenkai , Wang Xiaolei , Yan Jiang , Li Yongliang , Wang Wenwu
Published: April 2021

The interface passivation of the HfO2/Si0.7Ge0.3 stack is systematically investigated based on low-temperature ozone oxidation and Si-cap methods. Compared with the Al2O3/Si0.7Ge0.3 stack, the dispersive feature and interface state density (Dit) of the HfO2/Si0.7Ge0.3 stack MOS (Metal-Oxide-Semiconductor) capacitor under ozone direct oxidation (pre-O sample) increases obviously. This is because the tiny amounts of GeOx in the formed interlayer (IL) oxide layer are more likely to diffuse into HfO2 and cause the HfO2/Si0.7Ge0.3 interface to deteriorate. Moreover, a post-HfO2-deposition (post-O) ozone indirect oxidation is proposed for the HfO2/Si0.7Ge0.3 stack; it is found that compared with pre-O sample, the Dit of the post-O sample decreases by about 50% due to less GeOx available in the IL layer. This is because the amount of oxygen atoms reaching the interface of HfO2/Si0.7Ge0.3 decreases and the thickness of IL in the post-O sample also decreases. To further reduce the Dit of the HfO2/Si0.7Ge0.3 interface, a Si-cap passivation with the optimal thickness of 1 nm is developed and an excellent HfO2/Si0.7Ge0.3 interface with Dit of 1.53 × 1011 eV−1cm−2 @ E−Ev = 0.36 eV is attained. After detailed analysis of the chemical structure of the HfO2/IL/Si-cap/Si0.7Ge0.3 using X-ray photoelectron spectroscopy (XPS), it is confirmed that the excellent HfO2/Si0.7Ge0.3 interface is realized by preventing the formation of Hf-silicate/Hf-germanate and Si oxide originating from the reaction between HfO2 and Si0.7Ge0.3 substrate.
Preparation of Nanoscale Urushiol/PAN Films to Evaluate Their Acid Resistance and Protection of Functional PVP Films
Authors: Wu Kunlin , Shiu Bing-Chiuan , Zhang Ding , Shen Zhenhao , Liu Minghua , Lin Qi
Published: April 2021

Different amounts of urushiol were added to a fixed amount of polyacrylonitrile (PAN) to make nanoscale urushiol/PAN films by the electrospinning method. Electrospinning solutions were prepared by using dimethylformamide (DMF) as the solvent. Nanoscale urushiol/PAN films and conductive Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)(PEDOT:PSS)/polyvinyl pyrrolidone (PVP) films were prepared by electrospinning. In order to prepare an electrospun sandwich nanoscale film, urushiol/PAN films were deposited as both the top and bottom layers and PEDOT:PSS/PVP film as the inner layer. When the PAN to urushiol ratio was 7:5, the fiber diameter ranged between 150 nm and 200 nm. The single-layer urushiol/PAN film could not be etched after being immersed into 60%, 80%, and 100% sulfuric acid (H2SO4) for 30 min, which indicated the improved acid resistance of the PAN film. The urushiol/PAN film was used to fabricate the sandwich nanoscale films. When the sandwich film was immersed into 80% and 100% H2SO4 solutions for 30 min, the structure remained intact, and the conductive PVP film retained its original properties. Thus, the working environment tolerability of the functional PVP film was increased.
Silver Nanoparticles as Carriers of Anticancer Drugs for Efficient Target Treatment of Cancer Cells
Authors: Gomes Helena I. O. , Martins Catarina S. M. , Prior João A. V.
Published: April 2021

Since the last decade, nanotechnology has evolved rapidly and has been applied in several areas, such as medicine, pharmaceutical, microelectronics, aerospace, food industries, among others. The use of nanoparticles as drug carriers has been explored and presents several advantages, such as controlled and targeted release of loaded or coupled drugs, and the improvement of the drug’s bioavailability, in addition to others. However, they also have some limitations, related to their in vivo toxicity, which affects all organs including the healthy ones, and overall improvement in the disease treatment, which can be unnoticeable or minimal. Silver nanoparticles have been increasingly investigated due to their peculiar physical, chemical, and optical properties, which allows them to cover several applications, namely in the transport of drugs to a specific target in the body. Given the limitations of conventional cancer chemotherapy, which include low bioavailability and the consequent use of high doses that cause adverse effects, strategies that overcome these difficulties are extremely important. This review embraces an overview and presentation about silver nanoparticles used as anticancer drug carrier systems and focuses a discussion on the state of the art of silver nanoparticles exploited for transport of anticancer drugs and their influence on antitumor effects.
Hierarchical Microstructure of Tooth Enameloid in Two Lamniform Shark Species, Carcharias taurus and Isurus oxyrinchus
Authors: Wilmers Jana , Waldron Miranda , Bargmann Swantje
Published: April 2021

Shark tooth enameloid is a hard tissue made up of nanoscale fluorapatite crystallites arranged in a unique hierarchical pattern. This microstructural design results in a macroscopic material that is stiff, strong, and tough, despite consisting almost completely of brittle mineral. In this contribution, we characterize and compare the enameloid microstructure of two modern lamniform sharks, Isurus oxyrinchus (shortfin mako shark) and Carcharias taurus (spotted ragged-tooth shark), based on scanning electron microscopy images. The hierarchical microstructure of shark enameloid is discussed in comparison with amniote enamel. Striking similarities in the microstructures of the two hard tissues are found. Identical structural motifs have developed on different levels of the hierarchy in response to similar biomechanical requirements in enameloid and enamel. Analyzing these structural patterns allows the identification of general microstructural design principles and their biomechanical function, thus paving the way for the design of bioinspired composite materials with superior properties such as high strength combined with high fracture resistance.
Fabrication and Characterization of an Efficient Inverted Perovskite Solar Cells with POSS Passivating Hole Transport Layer
Authors: Liu Bo-Tau , Lin Hong-Ru , Lee Rong-Ho , Gorji Nima E. , Chou Jung-Chuan
Published: April 2021

Polyhedral oligomeric silsesquioxane (POSS), featuring a hollow-cage or semi-cage structure is a new type of organic–inorganic hybrid nanoparticles. POSS combines the advantages of inorganic components and organic components with a great potential for optoelectronic applications such as in emerging perovskite solar cells. When POSS is well dispersed in the polymer matrix, it can effectively improve the thermal, mechanical, magnetic, acoustic, and surface properties of the polymer. In this study, POSS was spin-coated as an ultra-thin passivation layer over the hole transporting layer of nickel-oxide (NOx) in the structure of a perovskite solar cell. The POSS incorporation led to a more hydrophobic and smoother surface for further perovskite deposition, resulting in the increase in the grain size of perovskite. An appropriate POSS passivation layer could effectively reduce the recombination of the electron and hole at grain boundaries and increase the short-circuit current from 18.0 to 20.5 mA·cm−2. Moreover, the open-circuit voltage of the cell could slightly increase over 1 V.
COVID-19 and Nanoscience in the Developing World: Rapid Detection and Remediation in Wastewater
Authors: Adeel Muhammad , Farooq Tahir , Shakoor Noman , Ahmar Sunny , Fiaz Sajid , White Jason C. , Gardea-Torresdey Jorge L. , Mora-Poblete Freddy , Rui Yukui
Published: April 2021

Given the known presence of SARS-Cov-2 in wastewater, stemming disease spread in global regions where untreated effluent in the environment is common will experience additional pressure. Though development and preliminary trials of a vaccine against SARS-CoV-2 have been launched in several countries, rapid and effective alternative tools for the timely detection and remediation of SARS-CoV-2 in wastewater, especially in the developing countries, is of paramount importance. Here, we propose a promising, non-invasive technique for early prediction and targeted detection of SARS-CoV-2 to prevent current and future outbreaks. Thus, a combination of nanotechnology with wastewater-based epidemiology and artificial intelligence could be deployed for community-level wastewater virus detection and remediation.
Alcohol Acutely Antagonizes Refeeding-Induced Alterations in the Rag GTPase-Ragulator Complex in Skeletal Muscle
Authors: Laufenberg Lacee J. , Crowell Kristen T. , Lang Charles H.
Published: April 2021

The Ragulator protein complex is critical for directing the Rag GTPase proteins and mTORC1 to the lysosome membrane mediating amino acid-stimulated protein synthesis. As there is a lack of evidence on alcohol’s effect on the Rag-Ragulator complex as a possible mechanism for the development of alcoholic skeletal muscle wasting, the aim of our study was to examine alterations in various protein–protein complexes in the Rag-Ragulator pathway produced acutely by feeding and how these are altered by alcohol under in vivo conditions. Mice (C57Bl/6; adult males) were fasted, and then provided rodent chow for 30 min (“refed”) or remained food-deprived (“fasted”). Mice subsequently received ethanol (3 g/kg ethanol) or saline intraperitoneally, and hindlimb muscles were collected 1 h thereafter for analysis. Refeeding-induced increases in myofibrillar and sarcoplasmic protein synthesis, and mTOR and S6K1 phosphorylation, were prevented by alcohol. This inhibition was not associated with a differential rise in the intracellular leucine concentration or plasma leucine or insulin levels. Alcohol increased the amount of the Sestrin1•GATOR2 complex in the fasted state and prevented the refeeding-induced decrease in Sestrin1•GATOR2 seen in control mice. Alcohol antagonized the increase in the RagA/C•Raptor complex formation seen in the refed state. Alcohol antagonized the increase in Raptor with immunoprecipitated LAMPTOR1 (part of the Ragulator complex) after refeeding and decreased the association of RagC with LAMPTOR1. Finally, alcohol increased the association of the V1 domain of v-ATPase with LAMPTOR1 and prevented the refeeding-induced decrease in v-ATPase V1 with LAMPTOR1. Overall, these data demonstrate that acute alcohol intake disrupts multiple protein–protein complexes within the Rag-Ragulator complex, which are associated with and consistent with the concomitant decline in nutrient-stimulated muscle protein synthesis under in vivo conditions.
Evaluation of E-Health Applications for Paediatric Patients with Refractory Epilepsy and Maintained on Ketogenic Diet
Authors: Costa Anna-Maria , Marchiò Maddalena , Bruni Giulia , Bernabei Silvia Maria , Cavalieri Silvia , Bondi Marina , Biagini Giuseppe
Published: April 2021

E-health technologies improve healthcare quality and disease management. The aim of this study was to develop a ketogenic diet management app as well as a website about this dietary treatment and to evaluate the benefits of giving caregivers access to various web materials designed for paediatric patients with refractory epilepsy. Forty families participated in the questionnaire survey, from January 2016 to March 2016. All caregivers were exposed to paper-based materials about the ketogenic diet, whereas only 22 received the app, called KetApp, and videos produced by dieticians. Caregivers with free access to web materials were more satisfied than the others with the informative material provided by the centre (p ≤ 0.001, Mann–Whitney test). Indeed, they showed a better attitude towards treatment, and they became more aware of dietary management in comparison to the control group (p ≤ 0.001). Moreover, caregivers provided with web materials were stimulated to pursue the treatment (p = 0.002) and to introduce it to their children and other people (p = 0.001). Additionally, caregivers supplied with web materials were more willing to help other families in choosing the ketogenic diet (p = 0.004). Overall, these findings indicate that web materials are beneficial for caregivers of paediatric patients with refractory epilepsy in our centres. Thus, the use of e-health applications could be a promising tool in the daily aspects of ketogenic diet management, and it is especially of value in the attempt to start or maintain the diet during the ongoing COVID-19 pandemic crisis.
Intravenous Lipid Emulsions Affect Respiratory Outcome in Preterm Newborn: A Case-Control Study
Authors: Boscarino Giovanni , Conti Maria Giulia , De Luca Francesca , Di Chiara Maria , Deli Giorgia , Bianchi Marco , Favata Paola , Cardilli Viviana , Di Nardo Giovanni , Parisi Pasquale , Terrin Gianluca
Published: April 2021

(1) Background: Hypertriglyceridemia (HiTG) is a metabolic complication of intravenous lipid emulsions (ILEs) infusion. We aimed to evaluate the influence of HiTG on the respiratory outcome of preterm babies; (2) Methods: We enrolled, in a case–control study, newborns with gestational age <32 weeks or birth weight <1500 g, over a 3-year period. They were divided into cases and controls; cases were defined by the detection of HiTG defined as serum triglycerides (TG) value >150 mg/dL; (3) Results: We enrolled 40 cases and 105 controls. Cases had an increased incidence of bronchopulmonary dysplasia (30.0% vs. 14.3%, p < 0.05) and longer duration of invasive mechanical ventilation (7 days, 95% CI 4–10 days vs. 4 days, 95% CI 1–7 days, p < 0.01) compared to controls. Multivariate analysis confirmed that HiTG independently influenced the duration of invasive mechanical ventilation, also in the subgroups with gestational age ≤28 + 6/7 weeks or birth weight ≤1000 g; (4) Conclusion: Newborns with HiTG related to ILEs had a longer duration of invasive mechanical ventilation. Temporary suspension or reduction in ILEs in the case of HiTG is associated with an improvement of respiratory outcome.
Micronutrient Deficiencies in Patients with Decompensated Liver Cirrhosis
Authors: Llibre-Nieto Gemma , Lira Alba , Vergara Mercedes , Solé Cristina , Casas Meritxell , Puig-Diví Valentí , Solé Gemma , Humanes Antonia , Grau Laia , Barradas Josep Maria , Miquel Mireia , Sánchez-Delgado Jordi
Published: April 2021

Patients with cirrhosis often develop malnutrition and micronutrient deficiencies, leading to a worse prognosis and increased mortality. Our main goal was to assess the prevalence of micronutrient deficiencies in patients with decompensated cirrhosis. This was a prospective single-center study including 125 consecutive patients hospitalized for acute decompensation of cirrhosis (mostly of alcoholic etiology). A blood test including trace elements and vitamins was performed on admission. The main micronutrient deficiencies observed were vitamin D (in 94.5%), vitamin A (93.5%), vitamin B6 (60.8%) and zinc (85.6%). Patients in Child-Pugh class C had lower levels of vitamin A (p < 0.0001), vitamin E (p = 0.01) and zinc (p < 0.001), and higher levels of ferritin (p = 0.002) and vitamin B12 (p < 0.001) than those in Child-Pugh class A and B. Patients with a higher model of end-stage liver disease (MELD) score had lower levels of vitamin A (p < 0.0001), vitamin E (p < 0.001), magnesium (p = 0.01) and zinc (p = 0.001), and higher levels of ferritin (p = 0.002) and vitamin B12 (p < 0.0001). Severe hepatic insufficiency correlated with lower levels of zinc, vitamin E and vitamin A, and higher levels of vitamin B12 and ferritin.
Microbial Pathogenicity in Space
Authors: Simões Marta Filipa , Antunes André
Published: April 2021

After a less dynamic period, space exploration is now booming. There has been a sharp increase in the number of current missions and also of those being planned for the near future. Microorganisms will be an inevitable component of these missions, mostly because they hitchhike, either attached to space technology, like spaceships or spacesuits, to organic matter and even to us (human microbiome), or to other life forms we carry on our missions. Basically, we never travel alone. Therefore, we need to have a clear understanding of how dangerous our “travel buddies” can be; given that, during space missions, our access to medical assistance and medical drugs will be very limited. Do we explore space together with pathogenic microorganisms? Do our hitchhikers adapt to the space conditions, as well as we do? Do they become pathogenic during that adaptation process? The current review intends to better clarify these questions in order to facilitate future activities in space. More technological advances are needed to guarantee the success of all missions and assure the reduction of any possible health and environmental risks for the astronauts and for the locations being explored.
Molecular Characterisation of Cryptosporidium spp. in Mozambican Children Younger than 5 Years Enrolled in a Matched Case-Control Study on the Aetiology of Diarrhoeal Disease
Authors: Messa Augusto , Köster Pamela C. , Garrine Marcelino , Nhampossa Tacilta , Massora Sérgio , Cossa Anélsio , Bassat Quique , Kotloff Karen , Levine Myron M. , Alonso Pedro L. , Carmena David , Mandomando Inácio
Published: April 2021

Cryptosporidium is a leading cause of childhood diarrhoea and associated physical and cognitive impairment in low-resource settings. Cryptosporidium-positive faecal samples (n = 190) from children aged ≤ 5 years enrolled in the Global Enteric Multicenter Study (GEMS) in Mozambique detected by ELISA (11.5%, 430/3754) were successfully PCR-amplified and sequenced at the gp60 or ssu rRNA loci for species determination and genotyping. Three Cryptosporidium species including C. hominis (72.6%, 138/190), C. parvum (22.6%, 43/190), and C. meleagridis (4.2%, 8/190) were detected. Children ≤ 23 months were more exposed to Cryptosporidium spp. infections than older children. Both C. hominis and C. parvum were more prevalent among children with diarrhoeal disease compared to those children without it (47.6% vs. 33.3%, p = 0.007 and 23.7% vs. 11.8%, p = 0.014, respectively). A high intra-species genetic variability was observed within C. hominis (subtype families Ia, Ib, Id, Ie, and If) and C. parvum (subtype families IIb, IIc, IIe, and IIi) but not within C. meleagridis (subtype family IIIb). No association between Cryptosporidium species/genotypes and child’s age was demonstrated. The predominance of C. hominis and C. parvum IIc suggests that most of the Cryptosporidium infections were anthroponotically transmitted, although zoonotic transmission events also occurred at an unknown rate. The role of livestock, poultry, and other domestic animal species as sources of environmental contamination and human cryptosporidiosis should be investigated in further molecular epidemiological studies in Mozambique.
Cat Respiratory Nematodes: Current Knowledge, Novel Data and Warranted Studies on Clinical Features, Treatment and Control
Authors: Morelli Simone , Diakou Anastasia , Colombo Mariasole , Di Cesare Angela , Barlaam Alessandra , Dimzas Dimitris , Traversa Donato
Published: April 2021

The nematodes Aelurostrongylus abstrusus, Troglostrongylus brevior and Capillaria aerophila are the most important parasites inhabiting the airways of cats. They are receiving growing attention from academia, pharmaceutical companies and veterinarians, and are now considered a primary cause of respiratory diseases in feline clinical practice and parasitology. In the past few years, several studies have been conducted in both natural and experimental settings to increase knowledge, provide new insights and fill gaps on respiratory parasitoses of cats. Awareness and knowledge of clinical scenarios towards appropriate and timely diagnosis and prompt and efficacious treatment options have become a priority to investigate. At the same time, chemopreventative approaches have been evaluated to assess the geographical spreading of these parasites and the rise in the number of clinical cases in cat populations of different countries. Given the intense accumulation of novel data, this review presents and discusses the state of the art and the latest updates on the clinical features, treatment, and control of major respiratory parasitoses of cats. Moreover, food for thought is also provided with the aim of spurring on new studies in the near future.
Healthy Photosynthetic Mechanism Suggests ISR Elicited by Bacillus spp. in Capsicum chinense Plants Infected with PepGMV
Authors: Samaniego-Gámez Blancka Yesenia , Garruña René , Tun-Suárez José M. , Moreno-Valenzuela Oscar A. , Reyes-Ramírez Arturo , Valle-Gough Raúl Enrique , Ail-Catzim Carlos Enrique , Toscano-Palomar Lydia
Published: April 2021

The aim of this study was to evaluate the effect of inoculation with Bacillus spp. isolates on the photosynthetic apparatus of Capsicum chinense plants infected with PepGMV. In vitro and greenhouse experiments were performed to evaluate whether the inoculation improved plants’ performance through the increase in photosynthetic efficiency to control PepGMV. The results showed that despite PepGMV infection, the plants inoculated with some isolates of Bacillus spp. had a healthy photosynthetic mechanism, as the photochemical parameters and gas exchange increased. The maximum photochemical quantum yield of PSII (Fv/Fm) of plants with PepGMV and inoculated with Bacillus isolates (M9, K46, and K47) increased (7.85, 7.09, and 7.77%, respectively) with respect to uninoculated controls. In inoculated plants, the CO2 assimilation rate increased and the transpiration rate decreased, therefore indicating an increased water use efficiency. This effect was reflected by the less severe symptoms caused by PepGMV in the plants obtained from seeds inoculated with different Bacillus spp. Plants inoculated with K47 isolates showed an increase in fruit yield and quality. This study suggests that it is possible to protect, at the greenhouse level, C. chinense plants from PepGMV through selected rhizobacteria inoculation.
Facile Synthesis and In Vitro Activity of N-Substituted 1,2-Benzisothiazol-3(2H)-ones against Dengue Virus NS2BNS3 Protease
Authors: Batool Farwa , Saeed Muhammad , Saleem Hafiza Nosheen , Kirschner Luisa , Bodem Jochen
Published: April 2021

Several new N-substituted 1,2-benzisothiazol-3(2H)-ones (BITs) were synthesised through a facile synthetic route for testing their anti-dengue protease inhibition. Contrary to the conventional multistep synthesis, we achieved structurally diverse BITs with excellent yields using a two-step, one-pot reaction strategy. All the synthesised compounds were prescreened for drug-like properties using the online Swiss Absorption, Distribution, Metabolism and Elimination (SwissADME) model, indicating their favourable pharmaceutical properties. Thus, the synthesised BITs were tested for inhibitory activity against the recombinant dengue virus serotype-2 (DENV-2) NS2BNS3 protease. Dose–response experiments and computational docking analyses revealed that several BITs bind to the protease in the vicinity of the catalytic triad with IC50 values in the micromolar range. The DENV2 infection assay showed that two BITs, 2-(2-chlorophenyl)benzo[d]isothiazol-3(2H)-one and 2-(2,6-dichlorophenyl)benzo[d]isothiazol-3(2H)-one, could suppress DENV replication and virus infectivity. These results indicate the potential of BITs for developing new anti-dengue therapeutics.
SARS-CoV-2 Ig G among Healthcare Workers and the General Population
Authors: Milani Gregorio P. , Bianchetti Mario G. , Togni Giuseppe , Schoenenberger Andreas W. , Muggli Franco
Published: April 2021

It is assumed that healthcare workers are at the highest risk to be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, few data from healthcare workers who do not primarily take care of patients with SARS-CoV-2 infection support this assumption. We investigated the prevalence of immunoglobulin G (Ig G) against SARS-CoV-2 among healthcare workers who do not primarily take care of patients with SARS-CoV-2 infection and the general population in a well-defined geographical area. The first part of the study was conducted in May 2020 in Val Mesolcina (Southern Switzerland), a valley with ~8000 inhabitants. All healthcare workers were invited. All participants (n = 488) of the Swiss Longitudinal Cohort Study (SWICOS), a cohort representative of the general population, were also invited. Circulating Ig G against spike protein subunit 1 of SARS-CoV-2 were tested in each subject. Subjects with positive Ig G were tested again after 6 months. The condition of being a healthcare worker, rather than a part of the general population, was tested as a predictor of seroprevalence positivity by both simple and multiple (adjusted for age and sex) logistic regression. Eleven (2.6%) of the 423 SWICOS participants and 46 (16%) out of 289 healthcare workers were positive for antibodies against SARS-CoV-2. The seroprevalence OR was 7.01 (95% CI: 3.53–15.47) for healthcare workers as compared to SWICOS participants. After adjusting for age and gender, the seroprevalence OR was 5.13 (95% CI: 2.54–10.40). About three quarters of the subjects in the SWICOS (73%) and in healthcare (79%) group with a previous positive serology still presented positive Ig G against the SARS-CoV-2 after 6 months. The present seroprevalence data point out that the SARS-CoV-2 infection is seven times higher among healthcare workers than in the general population of Val Mesolcina. Efforts to effectively protect all the healthcare personnel are needed.
Improving Breast Cancer Treatment Specificity Using Aptamers Obtained by 3D Cell-SELEX
Authors: Nelissen Frank H. T. , Peeters Wenny J. M. , Roelofs Timo P. , Nagelkerke Anika , Span Paul N. , Heus Hans A.
Published: April 2021

Three-dimensional spheroids of non-malignant MCF10A and malignant SKBR3 breast cells were used for subsequent 3D Cell-SELEX to generate aptamers for specific binding and treatment of breast cancer cells. Using 3D Cell-SELEX combined with Next-Generation Sequencing and bioinformatics, ten abundant aptamer families with specific structures were identified that selectively bind to SKBR3, and not to MCF10A cells. Multivalent aptamer polymers were synthesized by co-polymerization and analyzed for binding performance as well as therapeutic efficacy. Binding performance was determined by confocal fluorescence imaging and revealed specific binding and efficient internalization of aptamer polymers into SKBR3 spheroids. For therapeutic purposes, DNA sequences that intercalate the cytotoxic drug doxorubicin were co-polymerized into the aptamer polymers. Viability tests show that the drug-loaded polymers are specific and effective in killing SKBR3 breast cancer cells. Thus, the 3D-selected aptamers enhanced the specificity of doxorubicin against malignant over non-malignant breast cells. The innovative modular DNA aptamer platform based on 3D Cell SELEX and polymer multivalency holds great promise for diagnostics and treatment of breast cancer.
Preparation, Characterization, Swelling Potential, and In-Vitro Evaluation of Sodium Poly(Styrene Sulfonate)-Based Hydrogels for Controlled Delivery of Ketorolac Tromethamine
Authors: Suhail Muhammad , Fang Chih-Wun , Minhas Muhammad Usman , Wu Pao-Chu
Published: April 2021

The objective of the current study work was to fabricate sodium poly(styrene sulfonate-co-poly acrylic acid) (SPSPAA) hydrogels by using a free radical co-polymerization method for controlled delivery of ketorolac tromethamine (KT). Polymer (sodium poly(styrene sulfonate) (SPS) polymerized with monomer acrylic acid (AA) in the presence of initiator ammonium peroxodisulfate (APS) and cross-linker N′,N′-Methylene bisacrylamide (MBA). Different combinations of polymer, cross-linker and monomer, were employed for development of polymeric hydrogels. Various studies such as sol-gel, drug loading, dynamic swelling, and drug release studies were carried out to know the sol and gel portion of SPSPAA, swelling behavior of hydrogels at different pH media (1.2 and 7.4), quantification of drug loaded by fabricated hydrogels, and amount release of KT at pH 1.2 and 7.4. Higher dynamic swelling was found at pH 7.4 compared to pH 1.2, and as a result, greater percent release of drug was perceived at pH 7.4. Thermal stability, crystallinity, confirmation of functional groups and development of a new polymeric system, and surface morphology were evaluated via Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) respectively. The results showed that the present work could be used as a potential candidate for controlled delivery of KT.
Pharmacokinetic-Pharmacodynamic Modelling of Systemic IL13 Blockade by Monoclonal Antibody Therapy: A Free Assay Disguised as Total
Authors: Hood John , González-García Ignacio , White Nicholas , Marshall Leeron , Dubois Vincent F. S. , Vicini Paolo , Baverel Paul G.
Published: April 2021

A sequential pharmacokinetic (PK) and pharmacodynamic (PD) model was built with Nonlinear Mixed Effects Modelling based on data from a first-in-human trial of a novel biologic, MEDI7836. MEDI7836 is a human immunoglobulin G1 lambda (IgG1λ-YTE) monoclonal antibody, with an Fc modification to reduce metabolic clearance. MEDI7836 specifically binds to, and functionally neutralizes interleukin-13. Thirty-two healthy male adults were enrolled into a dose-escalation clinical trial. Four active doses were tested (30, 105, 300, and 600 mg) with 6 volunteers enrolled per cohort. Eight volunteers received placebo as control. Following single subcutaneous administration (SC), individual time courses of serum MEDI7836 concentrations, and the resulting serum IL13 modulation in vivo, were quantified. A binding pharmacokinetic-pharmacodynamic (PK-PD) indirect response model was built to characterize the exposure-driven modulation of the target over time by MEDI7836. While the validated bioanalytical assay specification quantified the level of free target (i.e., a free IL13 assay), emerging clinical data suggested dose-dependent increase in systemic IL13 concentration over time, indicative of a total IL13 assay. The target time course was modelled as a linear combination of free target and a percentage of the drug-target complex to fit the clinical data. This novel PK-PD modelling approach integrates independent knowledge about the assay characteristics to successfully elucidate apparently complex observations.
Simultaneous Visualization of 161Tb- and 177Lu-Labeled Somatostatin Analogues Using Dual-Isotope SPECT Imaging
Authors: Borgna Francesca , Barritt Patrick , Grundler Pascal V. , Talip Zeynep , Cohrs Susan , Zeevaart Jan Rijn , Köster Ulli , Schibli Roger , van der Meulen Nicholas P. , Müller Cristina
Published: April 2021

The decay of terbium-161 results in the emission of β¯-particles as well as conversion and Auger electrons, which makes terbium-161 interesting for therapeutic purposes. The aim of this study was to use dual-isotope SPECT imaging in order to demonstrate visually that terbium-161 and lutetium-177 are interchangeable without compromising the pharmacokinetic profile of the radiopharmaceutical. The 161Tb- and 177Lu-labeled somatostatin (SST) analogues DOTATOC (agonist) and DOTA-LM3 (antagonist) were tested in vitro to demonstrate equal properties regarding distribution coefficients and cell uptake into SST receptor-positive AR42J tumor cells. The radiopeptides were further investigated in AR42J tumor-bearing nude mice using the method of dual-isotope (terbium-161/lutetium-177) SPECT/CT imaging to enable the visualization of their distribution profiles in the same animal. Equal pharmacokinetic profiles were demonstrated for either of the two peptides, irrespective of whether it was labeled with terbium-161 or lutetium-177. Moreover, the visualization of the sub-organ distribution confirmed similar behavior of 161Tb- and 177Lu-labeled SST analogues. The data were verified in quantitative biodistribution studies using either type of peptide labeled with terbium-161 or lutetium-177. While the radionuclide did not have an impact on the organ distribution, this study confirmed previous data of a considerably higher tumor uptake of radiolabeled DOTA-LM3 as compared to the radiolabeled DOTATOC.
Assessment of the Biochemical Responses of Wheat Seedlings to Soil Drought after Application of Selective Herbicide
Authors: Todorova Dessislava , Sergiev Iskren , Katerova Zornitsa , Shopova Elena , Dimitrova Ljudmila , Brankova Liliana
Published: April 2021

Drought is a major environmental constrain with a deleterious effect on plant development leading to a considerable reduction of crop productivity worldwide. Wheat is a relatively drought tolerant crop during the vegetative stage. The herbicide Serrate® (Syngenta) is a preparation containing two active chemical substances with different modes of action, which inhibit the biosynthesis of fatty and amino acids. It is commonly used as a systemic and selective chemical agent to control annual grass and broadleaf weeds in cereal crops and particularly in wheat, which is tolerant to Serrate®. Seventeen-day-old wheat seedlings (Triticum aestivum L., cv. Sadovo-1) grown as soil culture under controlled conditions were sprayed with an aqueous solution of Serrate®. Seventy-two hours later the plantlets were subjected to drought stress for seven days to reach a severe water deficit followed by four days of recovery with a normal irrigation regime. Oxidative stress markers, non-enzymatic, and enzymatic antioxidants were analyzed in the leaves of plants from the different treatment groups (herbicide-treated, droughts-stressed, and individuals which were consecutively subjected to both treatments) at 0, 96, and 168 h of drought stress, and after 96 h of recovery. Herbicide treatment did not alter substantially the phenotype and growth parameters of the above-ground plant parts. It provoked a moderate increase in phenolics, thiol-containing compounds, catalase, superoxide dismutase, glutathione reductase, and H2O2. However, significant variations of malondialdehyde, proline, and peroxidase activity caused by the sole application of the herbicide were not detected during the experimental period. Drought and herbicide + drought treatments caused significant growth inhibition, increased oxidative stress markers, and activation of enzymatic and non-enzymatic antioxidant defense reaching the highest levels at 168 h of stress. Plant growth was restored after 96 h of recovery and the levels of the monitored biochemical parameters showed a substantial decline. The herbicide provoked an extra load of oxidative stress-related biochemical components which did not aggravate the phenotypic and growth traits of plants subjected to drought, since they exhibited a good physiological status upon recovery.
Effects of Benzoquinones on Radicles of Orobanche and Phelipanche Species
Authors: Fernández-Aparicio Mónica , Masi Marco , Cimmino Alessio , Evidente Antonio
Published: April 2021

The holoparasitic broomrape weeds (Orobanche and Phelipanche species) cause severe yield losses throughout North Africa, the Middle East, and Southern and Eastern Europe. These parasitic weeds form an haustorium at the tip of their radicles to infect the crop upon detection of the host-derived haustorium-inducing factors. Until now, the haustorial induction in the broomrapes remains less studied than in other parasitic plant species. Known haustorium-inducing factors active in hemiparasites, such as Striga and Triphysaria species, were reported to be inefficient for the induction of haustoria in broomrape radicles. In this work, the haustorium-inducing activity of p-benzoquinone and 2,6-dimethoxy-p-benzoquinone (BQ and DMBQ) on radicles of three different broomrapes, namely Orobanche cumana, Orobanche minor and Phelipanche ramosa, is reported. Additional allelopathic effects of benzoquinones on radicle growth and radicle necrosis were studied. The results of this work suggest that benzoquinones play a role in the induction of haustorium in broomrapes. Although dependent on the broomrape species assayed and the concentration of quinones used in the test, the activity of BQ appeared to be stronger than that of DMBQ. The redox property represented by p-benzoquinone, which operates in several physiological processes of plants, insects and animals, is invoked to explain this different activity. This work confirms the usefulness of benzoquinones as haustorium-inducing factors for holoparasitic plant research. The findings of this work could facilitate future studies in the infection process, such as host-plant recognition and haustorial formation.
Genetic Modification for Agriculture—Proposed Revision of GMO Regulation in Australia
Authors: Redden Robert
Published: April 2021

Genetic engineering (GM) of crops, modified with DNA transfer between species, has been highly regulated for over two decades. Now, genome editing (GE) enables a range of DNA alterations, from single base pair changes to precise gene insertion with site-directed nucleases (SDNs). Past regulations, established according to the precautionary principle of avoiding potential risks to human health and the environment, are predicated on fears fanned by well-funded and emotional anti-GM campaigns. These fears ignore the safety record of GM crops over the last 25 years and the benefits of GM to crop productivity, disease and pest resistance, and the environment. GE is now superseding GM, and public education is needed about its benefits and its potential to meet the challenges of climate change for crops. World population will exceed 9 billion by 2050, and world CO2 levels are now over 400 ppm in contrast with a pre-industrial 280 ppm, leading to a projected 1.5 °C global warming by 2050, with more stressful crop environments. The required abiotic and biotic stress tolerances can be introgressed from crop wild relatives (CWR) into domestic crops via GE. Restrictive regulations need to be lifted to facilitate GE technologies for sustainable agriculture in Australia and the world.