bluuebunny/crossref_metadata_2025 huggingface dataset:
High Correlation among Brain-Derived Major Protein Levels in Cerebrospinal Fluid: Implication for Amyloid-Beta and Tau Protein Changes in Alzheimer’s Disease
Authors: Hoshi Kyoka , Kanno Mayumi , Abe Mitsunari , Murakami Takenobu , Ugawa Yoshikazu , Goto Aya , Honda Takashi , Saito Takashi , Saido Takaomi C. , Yamaguchi Yoshiki , Miyajima Masakazu , Furukawa Katsutoshi , Arai Hiroyuki , Hashimoto Yasuhiro
Published: April 2022

The cerebrospinal fluid (CSF) plays an important role in homeostasis of the brain. We previously demonstrated that major CSF proteins such as lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin (Tf) that are biosynthesized in the brain could be biomarkers of altered CSF production. Here we report that the levels of these brain-derived CSF proteins correlated well with each other across various neurodegenerative diseases, including Alzheimer’s disease (AD). In addition, protein levels tended to be increased in the CSF samples of AD patients compared with the other diseases. Patients at memory clinics were classified into three categories, consisting of AD (n = 61), mild cognitive impairment (MCI) (n = 42), and cognitively normal (CN) (n = 23), with MMSE scores of 20.4 ± 4.2, 26.9 ± 1.7, and 29.0 ± 1.6, respectively. In each category, CSF protein levels were highly correlated with each other. In CN subjects, increased CSF protein levels correlated well with those of AD markers, including amyloid-β and tau protein, whereas in MCI and AD subjects, correlations declined with AD markers except p-tau. Future follow-up on each clinical subject may provide a clue that the CSF proteins would be AD-related biomarkers.
Study of Through-Hole Micro-Drilling in Sapphire by Means of Pulsed Bessel Beams
Authors: Kuriakose Akhil , Bollani Monica , Di Trapani Paolo , Jedrkiewicz Ottavia
Published: April 2022

Ultrashort Bessel beams have been used in this work to study the response of a 430-μm-thick monocrystalline sapphire sample to laser–matter interaction when injecting the beam orthogonally through the whole sample thickness. We show that with a 12° Bessel beam cone angle, we are able to internally modify the material and generate tailorable elongated microstructures while preventing the formation of surface cracks, even in the picosecond regime, contrary to what was previously reported in the literature. On the other hand, by means of Bessel beam machining combined with a trepanning technique where very high energy pulses are needed, we were able to generate 100 μm diameter through-holes, eventually with negligible cracks and very low taper angles thanks to an optimization achieved by using a 60-μm-thick layer of Kapton Polyimide removable tape.
Dimension Reduction Localization Algorithm of Mixed Sources Based on MEMS Vector Hydrophone Array
Authors: Shang Zhenzhen , Yang Libo , Zhang Wendong , Zhang Guojun , Zhang Xiaoyong , Kou Hairong
Published: April 2022

In this paper, a mixed sources dimension reduction Multiple Signal Classification (MUSIC) localization algorithm suitable for Micro-Electro-Mechanical System (MEMS) vector hydrophone linear arrays is proposed, which reduces the two-dimensional search to one-dimensional local search. Firstly, the Lagrangian function is constructed by quadratic optimization idea to obtain the estimates of azimuth angles. Secondly, the least square method is utilized for optimal match to obtain the direction-of-arrivals (DOAs) and ranges, and the range parameters are judged in Fresnel zone to obtain the azimuth information of all near-field sources. Finally, find the common DOAs and achieve high-resolution separation of far-field and near-field sources. Simulation and field experiments prove that the proposed algorithm only needs a small number of elements can solve the problem of port and starboard ambiguity, does not need to construct high-order cumulants or multi-dimensional search while the parameters are automatically matched with low computational complexity. This study provides an idea of the engineering application of vector hydrophone.
A High-Sensitivity Resonant Magnetic Sensor Based on Graphene Nanomechanical Resonator
Authors: Liu Wenyao , Li Wei , Liu Chenxi , Xing Enbo , Zhou Yanru , Liu Lai , Tang Jun
Published: April 2022

This paper presents a novel resonant magnetic sensor consisting of a graphene nanomechanical oscillator and magnetostrictive stress coupling structure, using Si/SiO2 substrate and Fe–Ga alloy, respectively. In this device, the deformation of the Fe–Ga alloy resulting from the external magnetic field changed the surface tension of the graphene, resulting in a significant change in the resonance frequency of graphene. Using the finite element analysis, it could be found that the response of the resonance frequency revealed a good linear relationship with the external magnetic field (along the x-axis) in the range of the 1 to 1.6 mT. By optimizing the sizes of each component of the magnetic sensor, such as the thickness of the Si/SiO2 substrate and the Fe–Ga alloy, and the length of the graphene, the sensitivity could even reach 834 kHz/mT, which is three orders of magnitude higher than conventional resonant magnetic devices. This provides a new method for highly sensitive and miniaturized magnetic sensors.
A Flexible Terahertz Metamaterial Biosensor for Cancer Cell Growth and Migration Detection
Authors: Fang Weihao , Lv Xiaoqing , Ma Zhengtai , Liu Jian , Pei Weihua , Geng Zhaoxin
Published: April 2022

Metamaterial biosensors have been extensively used to identify cell types and detect concentrations of tumor biomarkers. However, the methods for in situ and non-destruction measurement of cell migration, which plays a key role in tumor progression and metastasis, are highly desirable. Therefore, a flexible terahertz metamaterial biosensor based on parylene C substrate was proposed for label-free and non-destructive detection of breast cancer cell growth and migration. The maximum resonance peak frequency shift achieved 183.2 GHz when breast cancer cell MDA−MB−231 was cultured onto the surface of the metamaterial biosensor for 72 h. A designed polydimethylsiloxane (PDMS) barrier sheet was applied to detect the cell growth rate which was quantified as 14.9 µm/h. The experimental peak shift expressed a linear relationship with the covered area and a quadratic relationship with the distance, which was consistent with simulation results. Additionally, the cell migration indicated that the transform growth factor-β (TGF-β) promoted the cancer cell migration. The terahertz metamaterial biosensor shows great potential for the investigation of cell biology in the future.
High Precision 3D Printing for Micro to Nano Scale Biomedical and Electronic Devices
Authors: Muldoon Kirsty , Song Yanhua , Ahmad Zeeshan , Chen Xing , Chang Ming-Wei
Published: April 2022

Three dimensional printing (3DP), or additive manufacturing, is an exponentially growing process in the fabrication of various technologies with applications in sectors such as electronics, biomedical, pharmaceutical and tissue engineering. Micro and nano scale printing is encouraging the innovation of the aforementioned sectors, due to the ability to control design, material and chemical properties at a highly precise level, which is advantageous in creating a high surface area to volume ratio and altering the overall products’ mechanical and physical properties. In this review, micro/-nano printing technology, mainly related to lithography, inkjet and electrohydrodynamic (EHD) printing and their biomedical and electronic applications will be discussed. The current limitations to micro/-nano printing methods will be examined, covering the difficulty in achieving controlled structures at the miniscule micro and nano scale required for specific applications.
The Retrospective on Atypical Brucella Species Leads to Novel Definitions
Authors: Occhialini Alessandra , Hofreuter Dirk , Ufermann Christoph-Martin , Al Dahouk Sascha , Köhler Stephan
Published: April 2022

The genus Brucella currently comprises twelve species of facultative intracellular bacteria with variable zoonotic potential. Six of them have been considered as classical, causing brucellosis in terrestrial mammalian hosts, with two species originated from marine mammals. In the past fifteen years, field research as well as improved pathogen detection and typing have allowed the identification of four new species, namely Brucella microti, Brucella inopinata, Brucella papionis, Brucella vulpis, and of numerous strains, isolated from a wide range of hosts, including for the first time cold-blooded animals. While their genome sequences are still highly similar to those of classical strains, some of them are characterized by atypical phenotypes such as higher growth rate, increased resistance to acid stress, motility, and lethality in the murine infection model. In our review, we provide an overview of state-of-the-art knowledge about these novel Brucella sp., with emphasis on their phylogenetic positions in the genus, their metabolic characteristics, acid stress resistance mechanisms, and their behavior in well-established in cellulo and in vivo infection models. Comparison of phylogenetic classification and phenotypical properties between classical and novel Brucella species and strains finally lead us to propose a more adapted terminology, distinguishing between core and non-core, and typical versus atypical brucellae, respectively.
Responses of Soil Microbial Communities and Networks to Precipitation Change in a Typical Steppe Ecosystem of the Loess Plateau
Authors: Wang Yutao , Xie Yingzhong , Ma Hongbin , Zhang Yi , Zhang Juan , Zhang Hao , Luo Xu , Li Jianping
Published: April 2022

The response of microbial communities to changes in precipitation can regulate the nutrition cycling of terrestrial ecosystems, but the effect on the structure and interaction of microbial communities and the relationship with environmental factors in arid and semiarid areas are unclear. Here, a field simulation experiment using three precipitation gradients, 50% of normal precipitation (P50), normal precipitation (P100) and 150% of normal precipitation (P150), was carried out in the typical grassland of the Loess Plateau. We applied high-throughput sequencing and network analysis to explore the effect of precipitation changes to soil microbial communities. The results indicated that the structural composition of the microbial community responded to precipitation treatments dramatically. The Top 50 microbials were divided into resource-limited, drought-tolerant and sensitive groups based on their response to altered precipitation. The network of bacteria was more complex and stronger than fungi. Bacterial networks were less stable but more adaptable under drought than fungal. Increasing precipitation promoted the complication and firmness of fungi networks. These findings are crucial for revealing the effects of climate change on soil microbial communities in arid-land and elsewhere and can provide valuable guidance for ecological restoration and response to climate change of the Loess Plateau.
Where the Little Ones Play the Main Role—Picophytoplankton Predominance in the Soda and Hypersaline Lakes of the Carpathian Basin
Authors: Somogyi Boglárka , Felföldi Tamás , Boros Emil , Szabó Attila , Vörös Lajos
Published: April 2022

The extreme environmental conditions of the diverse saline inland waters (soda lakes and pans, hypersaline lakes and ponds) of the Carpathian Basin are an advantage for picophytoplankton. The abundance of picophytoplankton in these waters can be up to several orders of magnitude higher than that in freshwater shallow lakes, but differences are also found within different saline water types: higher picophytoplankton abundances were observed in hypersaline lakes compared to humic soda lakes, and their highest numbers were detected in turbid soda lakes. Moreover, their contribution to phytoplankton biomass is higher than that in shallow freshwater lakes with similar trophic states. Based on long-term data, their ratio within the phytoplankton increased with turbidity in the case of turbid soda lakes, while, in hypersaline lakes, their proportion increased with salinity. Picocyanobacteria were only detected with high abundance (>106–107 cells/mL) in turbid soda lakes, while picoeukaryotes occurred in high numbers in both turbid and hypersaline lakes. Despite the extreme conditions of the lakes, the diversity of picophytoplankton is remarkable, with the dominance of non-marine Synechococcus/Cyanobium, Choricystis, Chloroparva and uncultured trebouxiophycean green algae in the soda lakes, and marine Synechococcus and Picochlorum in the hypersaline lakes.
Potential Applications of Essential Oils for Environmental Sanitization and Antimicrobial Treatment of Intensive Livestock Infections
Authors: Mariotti Melinda , Lombardini Giulia , Rizzo Silvia , Scarafile Donatella , Modesto Monica , Truzzi Eleonora , Benvenuti Stefania , Elmi Alberto , Bertocchi Martina , Fiorentini Laura , Gambi Lorenzo , Scozzoli Maurizio , Mattarelli Paola
Published: April 2022

The extensive use of antibiotics has contributed to the current antibiotic resistance crisis. Livestock infections of Salmonella spp, Clostridium spp. and E. coli antimicrobial-resistant bacteria represent a public threat to human and animal health. To reduce the incidence of these zoonoses, essential oils (EOs) could be effective antibiotic alternatives. This study aims at identifying EOs safe for use, effective both in complementary therapy and in the environmental sanitization of intensive farming. Natural products were chemo-characterized by gas chromatography. Three S. Typhimurium, three C. perfringens and four E. coli strains isolated from poultry and swine farms were used to assess the antimicrobial properties of nine EOs and a modified GR-OLI (mGR-OLI). The toxicity of the most effective ones (Cinnamomum zeylanicum, Cz; Origanum vulgare, Ov) was also evaluated on porcine spermatozoa and Galleria mellonella larvae. Cz, Ov and mGR-OLI showed the strongest antimicrobial activity; their volatile components were also able to significantly inhibit the growth of tested strains. In vitro, Ov toxicity was slightly lower than Cz, while it showed no toxicity on G. mellonella larvae. In conclusion, the study confirms the importance of evaluating natural products to consolidate the idea of safe EO applications in reducing and preventing intensive livestock infections.
Effects of Rhizobia Isolated from Coffee Fields in the High Jungle Peruvian Region, Tested on Phaseolus vulgaris L. var. Red Kidney
Authors: Lirio-Paredes Jesus , Ogata-Gutiérrez Katty , Zúñiga-Dávila Doris
Published: April 2022

Soils in the high jungle region of Peru continuously face erosion due to heavy rain, which leads to significant nutrient losses. Leguminous plants may provide a sustainable solution to this problem due to their ability to fix atmospheric nitrogen with the help of symbiotic rhizospheric microbes that reside in their root nodules and help restore soil fertility. The aim of this study was to isolate native rhizobial strains that can form functional nodules in red kidney beans to help improve their growth, development, and yield in field conditions. Rhizobium strains were isolated from soil samples collected from coffee fields using bean plants as trap hosts. The strain RZC12 was selected because it showed good root nodule promotion and a number of PGPR (plant-growth-promoting rhizobacteria) attributes. In the field, bean plants inoculated with the strain RZC12 and co-cultivated with coffee plants produced approximately 21 nodules per plant, whereas control plants produced an average of 1 nodule each. The inoculation with RZC12 significantly increased plant length (72.7%), number of leaves (58.8%), fresh shoot weight (85.5%), dry shoot weight (78%), fresh root weight (85.7%), and dry root weight (82.5%), compared with the control. The dry pod weight produced by the plants inoculated with RZC12 was 3.8 g, whereas the control plants produced 2.36 g of pods. In conclusion, RZC12 is a promising strain that can be used in field conditions to improve the overall productivity of red kidney beans.
Red Blood Cell BCL-xL Is Required for Plasmodium falciparum Survival: Insights into Host-Directed Malaria Therapies
Authors: Boulet Coralie , Siddiqui Ghizal , Gaynor Taylah L. , Doerig Christian , Creek Darren J. , Carvalho Teresa G.
Published: April 2022

The development of antimalarial drug resistance is an ongoing problem threatening progress towards the elimination of malaria, and antimalarial treatments are urgently needed for drug-resistant malaria infections. Host-directed therapies (HDT) represent an attractive strategy for the development of new antimalarials with untapped targets and low propensity for resistance. In addition, drug repurposing in the context of HDT can lead to a substantial decrease in the time and resources required to develop novel antimalarials. Host BCL-xL is a target in anti-cancer therapy and is essential for the development of numerous intracellular pathogens. We hypothesised that red blood cell (RBC) BCL-xL is essential for Plasmodium development and tested this hypothesis using six BCL-xL inhibitors, including one FDA-approved compound. All BCL-xL inhibitors tested impaired proliferation of Plasmodium falciparum 3D7 parasites in vitro at low micromolar or sub-micromolar concentrations. Western blot analysis of infected cell fractions and immunofluorescence microscopy assays revealed that host BCL-xL is relocated from the RBC cytoplasm to the vicinity of the parasite upon infection. Further, immunoprecipitation of BCL-xL coupled with mass spectrometry analysis identified that BCL-xL forms unique molecular complexes with human μ-calpain in uninfected RBCs, and with human SHOC2 in infected RBCs. These results provide interesting perspectives for the development of host-directed antimalarial therapies and drug repurposing efforts.
Correction: Alhamami et al. First Emergence of Resistance to Macrolides and Tetracycline Identified in Mannheimia haemolytica and Pasteurella multocida Isolates from Beef Feedlots in Australia. Microorganisms 2021, 9, 1322
Authors: Alhamami Tamara , Roy Chowdhury Piklu , Gomes Nancy , Carr Mandi , Veltman Tania , Khazandi Manouchehr , Mollinger Joanne , Deutscher Ania T. , Turni Conny , Mahdi Layla , Venter Henrietta , Abraham Sam , Djordjevic Steven P. , Trott Darren J.
Published: April 2022

The authors wish to make the following corrections to this paper [...]
Marker-Free Genome Engineering in Amycolatopsis Using the pSAM2 Site-Specific Recombination System
Authors: Santos Luísa D. F. , Caraty-Philippe Laëtitia , Darbon Emmanuelle , Pernodet Jean-Luc
Published: April 2022

Actinobacteria of the genus Amycolatopsis are important for antibiotic production and other valuable biotechnological applications such as bioconversion or bioremediation. Despite their importance, tools and methods for their genetic manipulation are less developed than in other actinobacteria such as Streptomyces. We report here the use of the pSAM2 site-specific recombination system to delete antibiotic resistance cassettes used in gene replacement experiments or to create large genomic deletions. For this purpose, we constructed a shuttle vector, replicating in Escherichia coli and Amycolatopsis, expressing the integrase and the excisionase from the Streptomyces integrative and conjugative element pSAM2. These proteins are sufficient for site-specific recombination between the attachment sites attL and attR. We also constructed two plasmids, replicative in E. coli but not in Amycolatopsis, for the integration of the attL and attR sites on each side of a large region targeted for deletion. We exemplified the use of these tools in Amycolatopsis mediterranei by obtaining with high efficiency a marker-free deletion of one single gene in the rifamycin biosynthetic gene cluster or of the entire 90-kb cluster. These robust and simple tools enrich the toolbox for genome engineering in Amycolatopsis.
Microbial Community Composition and Activity in Saline Soils of Coastal Agro–Ecosystems
Authors: Dong Yang , Zhang Jianwei , Chen Ruirui , Zhong Linghao , Lin Xiangui , Feng Youzhi
Published: April 2022

Soil salinity is a serious problem for agriculture in coastal regions. Nevertheless, the effects of soil salinity on microbial community composition and their metabolic activities are far from clear. To improve such understanding, we studied microbial diversity, community composition, and potential metabolic activity of agricultural soils covering non–, mild–, and severe–salinity. The results showed that salinity had no significant effect on bacterial richness; however, it was the major driver of a shift in bacterial community composition and it significantly reduced microbial activity. Abundant and diverse of microbial communities were detected in the severe–salinity soils with an enriched population of salt–tolerant species. Co–occurrence network analysis revealed stronger dependencies between species associated with severe salinity soils. Results of microcalorimetric technology indicated that, after glucose amendment, there was no significant difference in microbial potential activity among soils with the three salinity levels. Although the salt prolonged the lag time of microbial communities, the activated microorganisms had a higher growth rate. In conclusion, salinity shapes soil microbial community composition and reduces microbial activity. An addition of labile organic amendments can greatly alleviate salt restrictions on microbial activity, which provides new insight for enhancing microbial ecological functions in salt–affected soils.
Development of a Model for the Separation Characteristics of a Deflector Wheel Classifier Including Particle Collision and Rebound Behavior
Authors: Weers Martin , Hansen Leonard , Schulz Daniel , Benker Bernd , Wollmann Annett , Kykal Carsten , Kruggel-Emden Harald , Weber Alfred P.
Published: April 2022

Deflector wheel classifiers are widespread in industry for the separation of powders into fine and coarse powders. Even though this separation process has been known for quite some time, it is not yet fully understood, and existing models fail to precisely predict the separation characteristics. Due to the high throughput of deflector wheel classifiers, it is greatly beneficial to estimate the separation characteristics before the experiment. Here, the developed model critically examines the usual assumptions, such as ideal airflow, neglection of particle–wall and particle–particle interactions, or spherically-shaped particles. First, the investigation of the air flow using a Particle Image Velocimetry (PIV) system showed significant differences to the assumed ideal flow field, then particle sphericity and its influence on the interaction between the particles and the paddles of the deflector wheel was investigated and compared with particle rebound behavior on a static wall. Surprisingly, comminuted glass behaves similarly to comminuted limestone in multiple aspects and not like glass beads. To determine the number of particle–particle collisions, Discrete Element Method (DEM) simulations were performed. The aforementioned aspects found application in the model and the separation behavior was well-estimated.
Historic Underground Silver Mine Workings Detection Using 2D Electrical Resistivity Imaging (Durango, Mexico)
Authors: Hinojosa Hector , Kirmizakis Panagiotis , Soupios Pantelis
Published: April 2022

This paper presents an underground silver mining operation outside Gomez Palacio, Durango, Mexico, terminated around the 1930s, of which previous knowledge of its operations was poor. Durango’s current silver exploration campaigns are likely to overlook historic silver mining sites due to interest in specific prospect regions. A two-dimensional (2D) Electrical Resistivity Imaging (ERI) survey coupled with reconnaissance of the area was performed at this historic silver mining site. The exploration campaign aimed to find the abandoned mineshaft, map its subsurface extent, and explore the occurrence of mineralization zones (silver ore). The ERI survey comprised five profiles measured with the extended dipole-dipole array with a consistent electrode spacing of 5 m. The smooth, robust, and damped least-squares inversion methods were used to invert the 2D data. Our field observations and ERI survey results collectively reveal the following findings: (a) reconnaissance reveals mining infrastructure consistent with historical mining activity; the infrastructure includes a complex of habitational rooms, an ore-processing pit near a concrete slab next to a dirt road, and two limestone-wall structures interpreted as the entrance of abandoned backfilled mineshafts named Mesquite and Lechuguilla; (b) high-resistivity anomalies suggest vestiges of shallow, underground mine workings including backfilled mineshafts that connect a mine gallery complex, and (c) various low-resistivity anomalies, juxtaposed against mine galleries, suggestive of unmined shallow vein-type and manto-type mineralization of hydrothermal origin. The imaging depth is estimated at ~65 m. Underground silver mining moved southwards and was limited to ~40 m depth.
First Evidence of Tris(catecholato)silicate Formation from Hydrolysis of an Alkyl Bis(catecholato)silicate
Authors: Campisciano Vincenzo , Taormina Benedetto , Spinella Alberto , Liotta Leonarda F. , Giacalone Francesco , Gruttadauria Michelangelo
Published: April 2022

The hydrolysis of 3-ammoniumpropylbis(catecholato)silicate 1, giving two different silica-based materials containing different amounts of tris(catecholato)silicate, is reported. The latter species can be formed through an attack of catechol to the silicon atom in the pentacoordinate complex, in which the silicon-carbon bond is further activated toward electrophilic proton cleavage. The Knoevenagel reaction was used as a probe in order to test the availability of functional groups on the surface of such materials.
Conformational Properties of New Thiosemicarbazone and Thiocarbohydrazone Derivatives and Their Possible Targets
Authors: Georgiou Nikitas , Katsogiannou Aikaterini , Skourtis Dimitrios , Iatrou Hermis , Tzeli Demeter , Vassiliou Stamatia , Javornik Uroš , Plavec Janez , Mavromoustakos Thomas
Published: April 2022

The structure assignment and conformational analysis of thiosemicarbazone KKI15 and thiocarbohydrazone KKI18 were performed through homonuclear and heteronuclear 2D Nuclear Magnetic Resonance (NMR) spectroscopy (2D-COSY, 2D-NOESY, 2D-HSQC, and 2D-HMBC) and quantum mechanics (QM) calculations using Functional Density Theory (DFT). After the structure identification of the compounds, various conformations of the two compounds were calculated using DFT. The two molecules showed the most energy-favorable values when their two double bonds adopted the E configuration. These configurations were compatible with the spatial correlations observed in the 2D-NOESY spectrum. In addition, due to the various isomers that occurred, the energy of the transition states from one isomer to another was calculated. Finally, molecular binding experiments were performed to detect potential targets for KKI15 and KKI18 derived from SwissAdme. In silico molecular binding experiments showed favorable binding energy values for all four enzymes studied. The strongest binding energy was observed in the enzyme butyrylcholinesterase. ADMET calculations using the preADMET and pKCSm software showed that the two molecules appear as possible drug leads.
Carbonic Anhydrase Activators for Neurodegeneration: An Overview
Authors: Poggetti Valeria , Salerno Silvia , Baglini Emma , Barresi Elisabetta , Da Settimo Federico , Taliani Sabrina
Published: April 2022

Carbonic anhydrases (CAs) are a family of ubiquitous metal enzymes catalyzing the reversible conversion of CO2 and H2O to HCO3− with the release of a proton. They play an important role in pH regulation and in the balance of body fluids and are involved in several functions such as homeostasis regulation and cellular respiration. For these reasons, they have been studied as targets for the development of agents for treating several pathologies. CA inhibitors have been used in therapy for a long time, especially as diuretics and for the treatment of glaucoma, and are being investigated for application in other pathologies including obesity, cancer, and epilepsy. On the contrary, CAs activators are still poorly studied. They are proposed to act as additional (other than histidine) proton shuttles in the rate-limiting step of the CA catalytic cycle, which is the generation of the active hydroxylated enzyme. Recent studies highlight the involvement of CAs activation in brain processes essential for the transmission of neuronal signals, suggesting CAs activation might represent a potential therapeutic approach for the treatment of Alzheimer’s disease and other conditions characterized by memory impairment and cognitive problems. Actually, some compounds able to activate CAs have been identified and proposed to potentially resolve problems related to neurodegeneration. This review reports on the primary literature regarding the potential of CA activators for treating neurodegeneration-related diseases.
GSH Protects the Escherichia coli Cells from High Concentrations of Thymoquinone
Authors: Łyżeń Robert , Gawron Grzegorz , Kadziński Leszek , Banecki Bogdan
Published: April 2022

The aim of the present study was to evaluate the potential protective effect of glutathione (GSH) on Escherichia coli cells grown in a high concentration of thymoquinone (TQ). This quinone, as the main active compound of Nigella sativa seed oil, exhibits a wide range of biological activities. At low concentrations, it acts as an antioxidant, and at high concentrations, an antimicrobial agent. Therefore, any interactions between thymoquinone and glutathione are crucial for cellular defense against oxidative stress. In this study, we found that GSH can conjugate with thymoquinone and its derivatives in vitro, and only fivefold excess of GSH was sufficient to completely deplete TQ and its derivatives. We also carried out studies on cultures of GSH-deficient Escherichia coli strains grown on a minimal medium in the presence of different concentrations of TQ. The strains harboring mutations in gene ΔgshA and ΔgshB were about two- and fourfold more sensitive (256 and 128 µg/mL, respectively) than the wild type. It was also revealed that TQ concentration has an influence on reactive oxygen species (ROS) production in E. coli strains—at the same thymoquinone concentration, the level of ROS was higher in GSH-deficient E. coli strains than in wild type.
Improved Synthesis of Asymmetric Curcuminoids and Their Assessment as Antioxidants
Authors: Cheng Yang-Je , Li Cai-Wei , Kuo Cing-Ling , Shih Tzenge-Lien , Chen Jih-Jung
Published: April 2022

In this paper, the syntheses of twelve asymmetric curcumin analogs using Pabon’s method are reported. Generally, the previously reported yields of asymmetric curcuminoids, such as 9a (53%), 9c (38%), and 9k (38%), have been moderate or low. Herein, we propose that the low yields were due to the presence of water and n-BuNH2 in the reaction media. To prove this formulated hypothesis, we have demonstrated that the yields can be improved by adding molecular sieves (MS) (4 Å) to the reaction mixture, thus reducing the interference of water. Therefore, improved yields (41–76%) were obtained, except for 9b (36.7%), 9g (34%), and 9l (39.5%). Furthermore, compounds 9b, 9d, 9e, 9f, 9g, 9h, 9i, 9j, and 9l are reported herein for the first time. The structures of these synthetic compounds were determined by spectroscopic and mass spectrometry analyses. The free radical scavenging ability of these synthetic asymmetric curcuminoids was evaluated and compared to that of the positive control butylated hydroxytoluene (BHT). Among the synthesized asymmetric curcuminoids, compounds 9a (IC50 = 37.57 ± 0.89 μM) and 9e (IC50 = 37.17 ± 1.76 μM) possessed effective 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging abilities, and compounds 9h (IC50 = 11.36 ± 0.65 μM) and 9i (IC50 = 10.91 ± 0.77 μM) displayed potent 2,2’-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical scavenging abilities comparable to that of curcumin (IC50 = 10.14 ± 1.04 μM). Furthermore, all the synthetic asymmetric curcuminoids were more active than BHT.
Effect of Co-Treatment of Olanzapine with SEP-363856 in Mice Models of Schizophrenia
Authors: Liang Lingzhi , Ren Xia , Xu Junyi , Ma Yurong , Xue Yunlin , Zhuang Tao , Zhang Guisen
Published: April 2022

Olanzapine is a commonly used drug in the treatment of schizophrenia, but its clinical application has been restricted by metabolic-related side effects. In order to mitigate the weight gain side effects caused by olanzapine, other drugs with different targets were selected for combined use and evaluated in animal models of schizophrenia. SEP-363856 is a novel psychotropic agent which is under phase III clinical trials for schizophrenia treatment. The aim of the research was to evaluate whether co-administration of olanzapine and SEP-363856 exerts synergistic anti-schizophrenic effects in the apomorphine (APO)-induced climbing test, the MK-801-induced hyperactivity test, and the Morris water maze test, and therefore reduces the weight gain side effects induced by olanzapine. Through isobolographic analysis, the results showed a synergistic interaction in the climbing test; the experimental ED30 (3 mg/kg) was significantly smaller (p < 0.05) than the theoretical ED30 (5 mg/kg). Additionally, such potentiating effects appeared additive in the MK-801 challenge experiment. Co-treatment with an effective dose of olanzapine and a low dose of SEP-363856 reversed MK-801-induced cognitive impairment symptoms in mice. Moreover, combination treatment with olanzapine and SEP-363856 controls sustained weight gain in mice with chronic exposure to olanzapine. These results support further clinical trials to test the effectiveness of co-treatment of olanzapine and SEP-363856 for controlling symptoms and weight gain in patients with schizophrenia during antipsychotic treatments.
Removal of the Harmful Nitrate Anions from Potable Water Using Different Methods and Materials, including Zero-Valent Iron
Authors: El-Lateef Hany M. Abd , Khalaf Mai M. , Al-Fengary Alaa El-dien , Elrouby Mahmoud
Published: April 2022

Drinking water containing nitrate ions at a higher concentration level of more than 10 mg/L, according to the World Health Organization (WHO), poses a considerable peril to humans. This danger lies in its reduction of nitrite ions. These ions cause methemoglobinemia during the oxidation of hemoglobin into methemoglobin. Many protocols can be applied to the remediation of nitrate ions from hydra solutions such as Zn metal and amino sulfonic acid. Furthermore, the electrochemical process is a potent protocol that is useful for this purpose. Designing varying parameters, such as the type of cathodic electrode (Sn, Al, Fe, Cu), the type of electrolyte, and its concentration, temperature, pH, and current density, can give the best conditions to eliminate the nitrate as a pollutant. Moreover, the use of accessible, functional, and inexpensive adsorbents such as granular ferric hydroxide, modified zeolite, rice chaff, chitosan, perlite, red mud, and activated carbon are considered a possible approach for nitrate removal. Additionally, biological denitrification is considered one of the most promising methodologies attributable to its outstanding performance. Among these powerful methods and materials exist zero-valent iron (ZVI), which is used effectively in the deletion process of nitrate ions. Non-precious synthesis pathways are utilized to reduce the Fe2+ or Fe3+ ions by borohydride to obtain ZVI. The structural and morphological characteristics of ZVI are elucidated using UV–Vis spectroscopy, zeta potential, XRD, FE-SEM, and TEM. The adsorptive properties are estimated through batch experiments, which are achieved to control the feasibility of ZVI as an adsorbent under the effects of Fe0 dose, concentration of NO3− ions, and pH. The obtained literature findings recommend that ZVI is an appropriate applicant adsorbent for the remediation of nitrate ions.
Synthesis and Antimycobacterial Evaluation of N-(4-(Benzyloxy)benzyl)-4-aminoquinolines
Authors: Grams Estevão Silveira , Silva Ramos Alessandro , Neves Muniz Mauro , Rambo Raoní S. , Alberton Perelló Marcia , Sperotto Nathalia , Calle González Laura , Duarte Lovaine Silva , Galina Luiza , Silva Dadda Adilio , Arraché Gonçalves Guilherme , Valim Bizarro Cristiano , Basso Luiz Augusto , Machado Pablo
Published: April 2022

Tuberculosis remains a global health problem that affects millions of people around the world. Despite recent efforts in drug development, new alternatives are required. Herein, a series of 27 N-(4-(benzyloxy)benzyl)-4-aminoquinolines were synthesized and evaluated for their ability to inhibit the M. tuberculosis H37Rv strain. Two of these compounds exhibited minimal inhibitory concentrations (MICs) similar to the first-line drug isoniazid. In addition, these hit compounds were selective for the bacillus with no significant change in viability of Vero and HepG2 cells. Finally, chemical stability, permeability and metabolic stability were also evaluated. The obtained data show that the molecular hits can be optimized aiming at the development of drug candidates for tuberculosis treatment.
A Significant Fluorescence Turn-On Probe for the Recognition of Al3+ and Its Application
Authors: Xing Zhiyong , Wang Junli , Huang Junhui , Chen Xiangfeng , Zong Ziao , Fan Chuanbin , Huang Guimei
Published: April 2022

An easy prepared probe, BHMMP, was designed and synthesized, which displayed a significant fluorescence enhancement (over 38-fold) and obvious color change in the recognition of Al3+. The binding ratio of probe BHMMP to Al3+ was determined as 1:1, according to Job plot. The binding mechanism was fully clarified by the experiments, such as FT-IR spectrum, ESI–MS analysis, and 1H NMR titration. A DFT study further confirmed the binding mode of BHMMP to Al3+. The limit of detection (LOD) for Al3+ was determined as low as 0.70 µM, based on the fluorescence titration of BHMMP. Moreover, the results from real sample experiments, including real water samples, test papers, and cell images, well-demonstrated that BHMMP was capable of sensing Al3+ in environmental and biological systems.
Silibinin and Naringenin against Bisphenol A-Induced Neurotoxicity in Zebrafish Model—Potential Flavonoid Molecules for New Drug Design, Development, and Therapy for Neurological Disorders
Authors: Thayumanavan Geethanjali , Jeyabalan Srikanth , Fuloria Shivkanya , Sekar Mahendran , Ravi Monica , Selvaraj Logesh Kumar , Bala Logeshwari , Chidambaram Kumarappan , Gan Siew Hua , Rani Nur Najihah Izzati Mat , Begum M. Yasmin , Subramaniyan Vetriselvan , Sathasivam Kathiresan V. , Meenakshi Dhanalekshmi U. , Fuloria Neeraj Kumar
Published: April 2022

Bisphenol A (BPA), a well-known xenoestrogen, is commonly utilised in the production of polycarbonate plastics. Based on the existing evidence, BPA is known to induce neurotoxicity and behavioural issues. Flavonoids such as silibinin and naringenin have been shown to have biological activity against a variety of illnesses. The current research evaluates the neuropharmacological effects of silibinin and naringenin in a zebrafish model against neurotoxicity and oxidative stress caused by Bisphenol A. In this study, a novel tank diving test (NTDT) and light–dark preference test (LDPT) were used in neurobehavioural investigations. The experimental protocol was planned to last 21 days. The neuroprotective effects of silibinin (10 μM) and naringenin (10 μM) in zebrafish (Danio rerio) induced by BPA (17.52 μM) were investigated. In the brine shrimp lethality assay, the 50% fatal concentrations (LC50) were 34.10 μg/mL (silibinin) and 91.33 μg/mL (naringenin) compared to the standard potassium dichromate (13.15 μg/mL). The acute toxicity investigation found no mortality or visible abnormalities in the silibinin- and naringenin-treated groups (LC50 > 100 mg/L). The altered scototaxis behaviour in LDPT caused by BPA was reversed by co-supplementation with silibinin and naringenin, as shown by decreases in the number of transitions to the light zone and the duration spent in the light zone. Our findings point to BPA’s neurotoxic potential in causing altered scototaxis and bottom-dwelling behaviour in zebrafish, as well as the usage of silibinin and naringenin as potential neuroprotectants.
Compositional Analysis of Four Kinds of Citrus Fruits with an NMR-Based Method for Understanding Nutritional Value and Rational Utilization: From Pericarp to Juice
Authors: Pei Yong , He Chenxi , Liu Huili , Shen Guiping , Feng Jianghua
Published: April 2022

Citrus is one of the most important economic crops and is widely distributed across the monsoon region. Citrus fruits are deeply loved by consumers because of their special color, fragrance and high nutritional value. However, their health benefits have not been fully understood, especially the pericarps of citrus fruits which have barely been utilized due to their unknown chemical composition. In the present study, the pericarp and juices of four typical varieties of citrus fruits (lemon, dekopon, sweet orange and pomelo) were analyzed by NMR spectroscopy combined with pattern recognition. A total of 62 components from the citrus juices and 87 components from the citrus pericarps were identified and quantified, respectively. The different varieties of the citrus fruits could be distinguished from the others, and the chemical markers in each citrus juice and pericarp were identified by a combination of univariate and multivariate statistical analyses. The nutritional analysis of citrus juices offers favorable diet recommendations for human consumption and data guidance for their potential medical use, and the nutritional analysis of citrus pericarps provides a data reference for the subsequent comprehensive utilization of citrus fruits. Our results not only provide an important reference for the potential nutritional and medical values of citrus fruits but also provide a feasible platform for the traceability analysis, adulteration identification and chemical composition analysis of other fruits.
A Comprehensive Investigation of Interactions between Antipsychotic Drug Quetiapine and Human Serum Albumin Using Multi-Spectroscopic, Biochemical, and Molecular Modeling Approaches
Authors: Zargar Seema , Wani Tanveer , Alsaif Nawaf , Khayyat Arwa
Published: April 2022

Quetiapine (QTP) is a short-acting atypical antipsychotic drug that treats schizophrenia or manic episodes of bipolar disorder. Human serum albumin (HSA) is an essential transport protein that transports hormones and various other ligands to their intended site of action. The interactions of QTP with HSA and their binding mechanism in the HSA-QTP system was studied using spectroscopic and molecular docking techniques. The UV-Vis absorption study shows hyperchromicity in the spectra of HSA on the addition of QTP, suggesting the complex formation and interactions between QTP and HSA. The results of intrinsic fluorescence indicate that QTP quenched the fluorescence of HSA and confirmed the complex formation between HSA and QTP, and this quenching mechanism was a static one. Thermodynamic analysis of the HSA-QTP system confirms the involvement of hydrophobic forces, and this complex formation is spontaneous. The competitive displacement and molecular docking experiments demonstrated that QTP is preferentially bound to HSA subdomain IB. Furthermore, the CD experiment results showed conformational changes in the HSA-QTP system. Besides this, the addition of QTP does not affect the esterase-like activity of HSA. This study will help further understand the credible mechanism of transport and delivery of QTP via HSA and design new QTP-based derivatives with greater efficacy.
Excretion, Metabolism, and Tissue Distribution of Gelsemium elegans (Gardn. & Champ.) Benth in Pigs
Authors: Ma Xiao , Wang Zi-Yuan , Zuo Meng-Ting , Yang Kun , Sun Zhi-Liang , Wu Yong , Liu Zhao-Ying
Published: April 2022

Gelsemium elegans (Gardn. & Champ.) Benth is a toxic flowering plant in the family Loganiaceae used to treat skin diseases, neuralgia and acute pain. The high toxicity of G. elegans restricts its development and clinical applications, but in veterinary applications, G. elegans has been fed to pigs as a feed additive without poisoning. However, until now, the in vivo processes of the multiple components of G. elegans have not been studied. This study investigates the excretion, metabolism and tissue distribution of the multiple components of G. elegans after feeding it to pigs in medicated feed. Pigs were fed 2% G. elegans powder in feed for 45 days. The plasma, urine, bile, feces and tissues (heart, liver, lung, spleen, brain, spinal cord, adrenal gland, testis, thigh muscle, abdominal muscle and back muscle) were collected 6 h after the last feeding and analyzed using high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Five natural products in plasma, twelve natural products and five metabolites in urine, and three natural products in feces were characterized, suggesting that multiple components from G. elegans were excreted in the urine. However, ten natural products and four metabolites were detected in bile samples, which suggested that G. elegans is involved in enterohepatic circulation in pigs. A total of seven of these metabolites were characterized, and four metabolites were glucuronidated metabolites. Ten natural products and six metabolites were detected in the tissues, which indicates that G. elegans is widely distributed in tissues and can cross the blood-brain barrier. Among the characterized compounds, a highly toxic gelsedine-type alkaloid from G. elegans was the main compound detected in all biological samples. This is the first study of the excretion, metabolism and tissue distribution of multiple components from G. elegans in pigs. These data can provide an important reference to explain the efficacy and toxicity of G. elegans. Additionally, the results of the tissue distribution of G. elegans are of great value for further residue depletion studies and safety evaluations of products of animals fed G. elegans.
Methods of Detecting Medication Administration Point-of-Care Errors in Acute Adult Inpatient Settings: A Scoping Review Protocol
Authors: Martyn Julie-Anne , Ratsch Angela , Cumming Kaye , Dredge Jennifer
Published: April 2022

Medication administration is recognized as a risk-prone activity where errors and near misses have multiple opportunities to occur along the route from manufacturing, through transportation, storage, prescription, dispensing, point-of-care administration, and post-administration documentation. While substantial research, education, and tools have been invested in the detection of medication errors on either side of point-of-care administration, less attention has been placed on this finite phase, leaving a gap in the error detection process. This protocol proposes to undertake a scoping review of the literature related to the detection of medication errors at the point-of-care to understand the potential size, nature, and extent of available literature. The aim is to identify research evidence to guide clinical practice and future research at the medication and patient point-of-care intersection. The search strategy will review literature from PubMed, CINAHL, Cochrane Collaboration, Embase, Scopus, PsychInfo, Web of Science, TRIP, TROVE, JBI Systematic Reviews, Health Collection (Informit), Health Source Nursing Academic, Prospero, Google Scholar, and graylit.org dated 1 January 2000–31 December 2021. Two independent reviewers will screen the literature for relevancy to the review objective, and critically appraise the citations for quality, validity, and reliability using the Joanna Briggs scoping review methodology and System for Unified Management, Assessment and Review of Information (SUMARI) tool. The data will be systematically synthesized to identify and compare the medication error administration detection method findings. A descriptive narrative discussion will accompany the findings.