bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 Spread Forecasting, Mathematical Methods vs. Machine Learning, Moscow Case
Authors: Pavlyutin Matvey , Samoyavcheva Marina , Kochkarov Rasul , Pleshakova Ekaterina , Korchagin Sergey , Gataullin Timur , Nikitin Petr , Hidirova Mohiniso
Published: January 2022

To predict the spread of the new coronavirus infection COVID-19, the critical values of spread indicators have been determined for deciding on the introduction of restrictive measures using the city of Moscow as an example. A model was developed using classical methods of mathematical modeling based on exponential regression, the accuracy of the forecast was estimated, and the shortcomings of mathematical methods for predicting the spread of infection for more than two weeks. As a solution to the problem of the accuracy of long-term forecasts for more than two weeks, two models based on machine learning methods are proposed: a recurrent neural network with two layers of long short-term memory (LSTM) blocks and a 1-D convolutional neural network with a description of the choice of an optimization algorithm. The forecast accuracy of ML models was evaluated in comparison with the exponential regression model and one another using the example of data on the number of COVID-19 cases in the city of Moscow.
Neurodidactics of Languages: Neuromyths in Multilingual Learners
Authors: Navarro Rincón Antonia , Carrillo López María José , Solano Galvis César Augusto , Isla Navarro Laura
Published: January 2022

From the perspective of neuroscience applied to education and the teaching of foreign languages, this exploratory study analyzes the beliefs and conceptions about the functioning of the brain and language learning in students enrolled in Education degrees at the Melilla campus of the University of Granada. The sample consisted of 397 participants. The data collection was carried out by means of a questionnaire designed for this purpose, consisting of questions related to the context and linguistic background of the respondents and to educational neuromyths regarding language learning. The data were analyzed using the SPSS version 27 statistical software, and univariate and bivariate analyses were carried out according to the three grouping dimensions: (a) brain functioning, (b) multiple intelligences and learning styles, and (c) language learning. The results indicate the prevalence of neuromyths related to general concepts, which determine the learning comprehension. This corroborates the findings of research studies in other contexts. Although the participants do not show a prevalence of neuromyths regarding foreign language learning, presumably due to their experiences in multilingual contexts, which constitutes the main contribution of this study.
Dynamic Analysis of Software Systems with Aperiodic Impulse Rejuvenation
Authors: Huo Huixia , Xu Houbao , Chen Zhuoqian
Published: January 2022

This paper aims to obtain the dynamical solution and instantaneous availability of software systems with aperiodic impulse rejuvenation. Firstly, we formulate the generic system with a group of coupled impulsive differential equations and transform it into an abstract Cauchy problem. Then we adopt a difference scheme and establish the convergence of this scheme by applying the Trotter–Kato theorem to obtain the system’s dynamical solution. Moreover, the instantaneous availability as an important evaluation index for software systems is derived, and its range is also estimated. At last, numerical examples are shown to illustrate the validity of theoretical results.
Bioactive Marine Xanthones: A Review
Authors: Soares José X. , Loureiro Daniela R. P. , Dias Ana Laura , Reis Salete , Pinto Madalena M. M. , Afonso Carlos M. M.
Published: January 2022

The marine environment is an important source of specialized metabolites with valuable biological activities. Xanthones are a relevant chemical class of specialized metabolites found in this environment due to their structural variety and their biological activities. In this work, a comprehensive literature review of marine xanthones reported up to now was performed. A large number of bioactive xanthone derivatives (169) were identified, and their structures, biological activities, and natural sources were described. To characterize the chemical space occupied by marine-derived xanthones, molecular descriptors were calculated. For the analysis of the molecular descriptors, the xanthone derivatives were grouped into five structural categories (simple, prenylated, O-heterocyclic, complex, and hydroxanthones) and six biological activities (antitumor, antibacterial, antidiabetic, antifungal, antiviral, and miscellaneous). Moreover, the natural product-likeness and the drug-likeness of marine xanthones were also assessed. Marine xanthone derivatives are rewarding bioactive compounds and constitute a promising starting point for the design of other novel bioactive molecules.
Importance of Osseoperception and Tactile Sensibility during Masticatory Function in Different Prosthetic Rehabilitations: A Review
Authors: González-Gil Diego , Dib-Zaitum Ibrahim , Flores-Fraile Javier , López-Marcos Joaquín
Published: January 2022

Background and Objectives: Tactile sensibility is an important characteristic for evaluating the masticatory efficiency in different occlusal situations. When a tooth is extracted, relevant proprioceptors from the periodontal ligament get lost; and after the rehabilitation of this abscess by means of oral prosthesis, this sensibility decreases influencing masticatory function. Osseoperception is a sensitive phenomenon associated with dental implants that allows an increased tactile sensibility to those wearing implant prostheses. The purpose of this study was to determine the difference in tactile sensibility values between implant prosthesis, complete dentures, and natural teeth through a review of the available literature. Materials and Methods. In order to dissect the information, 24 articles from 2004 to 2021 were analyzed from MEDLINE, PubMed Central, and Web of Science databases. These articles were directly related to measuring tactile sensibility in different situations and demonstrating the influence of osseoperception in an improved masticatory function. Results: Tactile sensibility in implant prosthesis is slightly reduced compared with natural dentition but presents improved values with regard to complete dentures. Conclusions: Implant prosthesis are more effective during masticatory function than complete dentures, as they present an increased tactile sensibility, very similar to that present in natural dentition. This enhanced sensibility in implants is due to the osseoperception phenomenon.
Psychogenic Pseudosyncope: Real or Imaginary? Results from a Case-Control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients
Authors: van Campen C. (Linda) M. C. , Visser Frans C.
Published: January 2022

Background and objectives: Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Exact numbers on syncopal spells especially if they are on a weekly or even daily basis are not described. Although not a frequent phenomenon, this symptomatology is of very high burden to the patient if present. To explore whether patients with very frequent (pre)syncope spells diagnosed elsewhere with conversion or psychogenic pseudosyncope (PPS) might have another explanation of their fainting spells than behavioral psychiatric disorders, we performed a case–control study comparing ME/CFS patients with and without PPS spells. Methods and results: We performed a case–control study in 30 ME/CFS patients diagnosed elsewhere with PPS and compared them with 30 control ME/CFS patients without syncopal spells. Cases were gender, age and ME/CFS disease duration matched. Each underwent a tilt test with extracranial Doppler measurements for cerebral blood flow (CBF). ME/CFS cases with PPS had a significant larger CBF reduction at end tilt than controls: 39 (6)% vs. 25 (4)%; (p < 0.0001). Cases had more severe disease compared with controls (chi-square p < 0.01 and had a p = 0.01) for more postural orthostatic tachycardia syndrome in cases compared with controls. PETCO2 end-tilt differed also, but the magnitude of difference was smaller than compared with the CBF reduction: there were no differences in heart rate and blood pressure at either end-tilt testing period. Compared with the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 25 (5) mmHg versus 29 (4) mmHg (p < 0.005). Conclusions: This study demonstrates that in ME/CFS patients suspected of having PPS, or conversion, CBF measurements end-tilt show a large decline compared with a control group of ME/CFS patients. Therefore, hypoperfusion offers an explanation of the orthostatic intolerance and syncopal spells in these patients, where it is clear that origin might not be behavioral or psychogenic, but have a clear somatic pathophysiologic background.
Changes in Oxygen Availability during Glucose-Limited Chemostat Cultivations of Penicillium chrysogenum Lead to Rapid Metabolite, Flux and Productivity Responses
Authors: Yang Qi , Lin Wenli , Xu Jiawei , Guo Nan , Zhao Jiachen , Wang Gaoya , Wang Yongbo , Chu Ju , Wang Guan
Published: January 2022

Bioreactor scale-up from the laboratory scale to the industrial scale has always been a pivotal step in bioprocess development. However, the transition of a bioeconomy from innovation to commercialization is often hampered by performance loss in titer, rate and yield. These are often ascribed to temporal variations of substrate and dissolved oxygen (for instance) in the environment, experienced by microorganisms at the industrial scale. Oscillations in dissolved oxygen (DO) concentration are not uncommon. Furthermore, these fluctuations can be exacerbated with poor mixing and mass transfer limitations, especially in fermentations with filamentous fungus as the microbial cell factory. In this work, the response of glucose-limited chemostat cultures of an industrial Penicillium chrysogenum strain to different dissolved oxygen levels was assessed under both DO shift-down (60% → 20%, 10% and 5%) and DO ramp-down (60% → 0% in 24 h) conditions. Collectively, the results revealed that the penicillin productivity decreased as the DO level dropped down below 20%, while the byproducts, e.g., 6-oxopiperidine-2-carboxylic acid (OPC) and 6-aminopenicillanic acid (6APA), accumulated. Following DO ramp-down, penicillin productivity under DO shift-up experiments returned to its maximum value in 60 h when the DO was reset to 60%. The result showed that a higher cytosolic redox status, indicated by NADH/NAD+, was observed in the presence of insufficient oxygen supply. Consistent with this, flux balance analysis indicated that the flux through the glyoxylate shunt was increased by a factor of 50 at a DO value of 5% compared to the reference control, favoring the maintenance of redox status. Interestingly, it was observed that, in comparison with the reference control, the penicillin productivity was reduced by 25% at a DO value of 5% under steady state conditions. Only a 14% reduction in penicillin productivity was observed as the DO level was ramped down to 0. Furthermore, intracellular levels of amino acids were less sensitive to DO levels at DO shift-down relative to DO ramp-down conditions; this difference could be caused by different timescales between turnover rates of amino acid pools (tens of seconds to minutes) and DO switches (hours to days at steady state and minutes to hours at ramp-down). In summary, this study showed that changes in oxygen availability can lead to rapid metabolite, flux and productivity responses, and dynamic DO perturbations could provide insight into understanding of metabolic responses in large-scale bioreactors.
Ubiquitous Aberration in Cholesterol Metabolism across Pancreatic Ductal Adenocarcinoma
Authors: Gunda Venugopal , Genaro-Mattos Thiago C. , Kaushal Jyoti B. , Chirravuri-Venkata Ramakanth , Natarajan Gopalakrishnan , Mallya Kavita , Grandgenett Paul M. , Mirnics Karoly , Batra Surinder K. , Korade Zeljka , Rachagani Satyanarayana
Published: January 2022

Pancreatic cancer (PC) is characterized by metabolic deregulations that often manifest as deviations in metabolite levels and aberrations in their corresponding metabolic genes across the clinical specimens and preclinical PC models. Cholesterol is one of the critical metabolites supporting PC, synthesized or acquired by PC cells. Nevertheless, the significance of the de novo cholesterol synthesis pathway has been controversial in PC, indicating the need to reassess this pathway in PC. We utilized preclinical models and clinical specimens of PC patients and cell lines and utilized mass spectrometry-based sterol analysis. Further, we also performed in silico analysis to corroborate the significance of de novo cholesterol synthesis pathway in PC. Our results demonstrated alteration in free sterol levels, including free cholesterol, across in vitro, in vivo, and clinical specimens of PC. Especially, our sterol analyses established consistent alterations in free cholesterol across the different PC models. Overall, this study demonstrates the significance and consistency in deviation of cholesterol synthesis pathway in PC while showing the aberrations in sterol metabolite intermediates and the related genes using preclinical models, in silico platforms, and the clinical specimens.
Mass Spectrometry Imaging Disclosed Spatial Distribution of Defense-Related Metabolites in Triticum spp.
Authors: Righetti Laura , Gottwald Sven , Tortorella Sara , Spengler Bernhard , Bhandari Dhaka Ram
Published: January 2022

Fusarium Head Blight is the most common fungal disease that strongly affects Triticum spp., reducing crop yield and leading to the accumulation of toxic metabolites. Several studies have investigated the plant metabolic response to counteract mycotoxins accumulation. However, information on the precise location where the defense mechanism is taking place is scarce. Therefore, this study aimed to investigate the specific tissue distribution of defense metabolites in two Triticum species and use this information to postulate on the metabolites’ functional role, unlocking the “location-to-function” paradigm. To address this challenge, transversal cross-sections were obtained from the middle of the grains. They were analyzed using an atmospheric-pressure (AP) SMALDI MSI source (AP-SMALDI5 AF, TransMIT GmbH, Giessen, Germany) coupled to a Q Exactive HF (Thermo Fisher Scientific GmbH, Bremen, Germany) orbital trapping mass spectrometer. Our result revealed the capability of (AP)-SMALDI MSI instrumentation to finely investigate the spatial distribution of wheat defense metabolites, such as hydroxycinnamic acid amides, oxylipins, linoleic and α-linoleic acids, galactolipids, and glycerolipids.
Identification and Distribution of Sterols, Bile Acids, and Acylcarnitines by LC–MS/MS in Humans, Mice, and Pigs—A Qualitative Analysis
Authors: Babu Ambrin Farizah , Koistinen Ville Mikael , Turunen Soile , Solano-Aguilar Gloria , Urban Joseph F. , Zarei Iman , Hanhineva Kati
Published: January 2022

Sterols, bile acids, and acylcarnitines are key players in human metabolism. Precise annotations of these metabolites with mass spectrometry analytics are challenging because of the presence of several isomers and stereoisomers, variability in ionization, and their relatively low concentrations in biological samples. Herein, we present a sensitive and simple qualitative LC–MS/MS (liquid chromatography with tandem mass spectrometry) method by utilizing a set of pure chemical standards to facilitate the identification and distribution of sterols, bile acids, and acylcarnitines in biological samples including human stool and plasma; mouse ileum, cecum, jejunum content, duodenum content, and liver; and pig bile, proximal colon, cecum, heart, stool, and liver. With this method, we detected 24 sterol, 32 bile acid, and 27 acylcarnitine standards in one analysis that were separated within 13 min by reversed-phase chromatography. Further, we observed different sterol, bile acid, and acylcarnitine profiles for the different biological samples across the different species. The simultaneous detection and annotation of sterols, bile acids, and acylcarnitines from reference standards and biological samples with high precision represents a valuable tool for screening these metabolites in routine scientific research.
Gut Microbiota Metabolites in Major Depressive Disorder—Deep Insights into Their Pathophysiological Role and Potential Translational Applications
Authors: Ortega Miguel A. , Alvarez-Mon Miguel Angel , García-Montero Cielo , Fraile-Martinez Oscar , Guijarro Luis G. , Lahera Guillermo , Monserrat Jorge , Valls Paula , Mora Fernando , Rodríguez-Jiménez Roberto , Quintero Javier , Álvarez-Mon Melchor
Published: January 2022

The gut microbiota is a complex and dynamic ecosystem essential for the proper functioning of the organism, affecting the health and disease status of the individuals. There is continuous and bidirectional communication between gut microbiota and the host, conforming to a unique entity known as “holobiont”. Among these crosstalk mechanisms, the gut microbiota synthesizes a broad spectrum of bioactive compounds or metabolites which exert pleiotropic effects on the human organism. Many of these microbial metabolites can cross the blood–brain barrier (BBB) or have significant effects on the brain, playing a key role in the so-called microbiota-gut-brain axis. An altered microbiota-gut-brain (MGB) axis is a major characteristic of many neuropsychiatric disorders, including major depressive disorder (MDD). Significative differences between gut eubiosis and dysbiosis in mental disorders like MDD with their different metabolite composition and concentrations are being discussed. In the present review, the main microbial metabolites (short-chain fatty acids -SCFAs-, bile acids, amino acids, tryptophan -trp- derivatives, and more), their signaling pathways and functions will be summarized to explain part of MDD pathophysiology. Conclusions from promising translational approaches related to microbial metabolome will be addressed in more depth to discuss their possible clinical value in the management of MDD patients.
Mouse Microglial Calcitonin Receptor Knockout Impairs Hypothalamic Amylin Neuronal pSTAT3 Signaling but Lacks Major Metabolic Consequences
Authors: Coester Bernd , Lutz Thomas A. , Le Foll Christelle
Published: January 2022

Amylin and leptin synergistically interact in the arcuate nucleus of the hypothalamus (ARC) to control energy homeostasis. Our previous rodent studies suggested that amylin-induced interleukin-6 release from hypothalamic microglia may modulate leptin signaling in agouti-related peptide expressing neurons. To confirm the physiological relevance of this finding, the calcitonin receptor (CTR) subunit of the amylin receptor was selectively depleted in microglia by crossing tamoxifen (Tx) inducible Cx3cr1-CreERT2 mice with CTR-floxed mice. Unexpectedly, male mice with CTR-depleted microglia (KO) gained the least amount of weight of all groups regardless of diet. However, after correcting for the tamoxifen effect, there was no significant difference for body weight, fat mass or lean mass between genotypes. No alteration in glucose tolerance or insulin release was detected. However, male KO mice had a reduced respiratory quotient suggesting a preference for fat as a fuel when fed a high fat diet. Importantly, amylin-induced pSTAT3 was decreased in the ARC of KO mice but this was not reflected in a reduced anorectic response. On the other hand, KO mice seemed to be less responsive to leptin’s anorectic effect while displaying similar ARC pSTAT3 as Tx-control mice. Together, these data suggest that microglial amylin signaling is not a major player in the control of energy homeostasis in mice.
Automated Sample Preparation and Data Collection Workflow for High-Throughput In Vitro Metabolomics
Authors: Malinowska Julia M. , Palosaari Taina , Sund Jukka , Carpi Donatella , Lloyd Gavin R. , Weber Ralf J. M. , Whelan Maurice , Viant Mark R.
Published: January 2022

Regulatory bodies have started to recognise the value of in vitro screening and metabolomics as two types of new approach methodologies (NAMs) for chemical risk assessments, yet few high-throughput in vitro toxicometabolomics studies have been reported. A significant challenge is to implement automated sample preparation of the low biomass samples typically used for in vitro screening. Building on previous work, we have developed, characterised and demonstrated an automated sample preparation and analysis workflow for in vitro metabolomics of HepaRG cells in 96-well microplates using a Biomek i7 Hybrid Workstation (Beckman Coulter) and Orbitrap Elite (Thermo Scientific) high-resolution nanoelectrospray direct infusion mass spectrometry (nESI-DIMS), across polar metabolites and lipids. The experimental conditions evaluated included the day of metabolite extraction, order of extraction of samples in 96-well microplates, position of the 96-well microplate on the instrument’s deck and well location within a microplate. By using the median relative standard deviation (mRSD (%)) of spectral features, we have demonstrated good repeatability of the workflow (final mRSD < 30%) with a low percentage of features outside the threshold applied for statistical analysis. To improve the quality of the automated workflow further, small method modifications were made and then applied to a large cohort study (4860 sample infusions across three nESI-DIMS assays), which confirmed very high repeatability of the whole workflow from cell culturing to metabolite measurements, whilst providing a significant improvement in sample throughput. It is envisioned that the automated in vitro metabolomics workflow will help to advance the application of metabolomics (as a part of NAMs) in chemical safety, primarily as an approach for high throughput screening and prioritisation.
Metabolic Profile Characterization of Different Thyroid Nodules Using FTIR Spectroscopy: A Review
Authors: Neto Vanessa , Esteves-Ferreira Sara , Inácio Isabel , Alves Márcia , Dantas Rosa , Almeida Idália , Guimarães Joana , Azevedo Teresa , Nunes Alexandra
Published: January 2022

Thyroid cancer’s incidence has increased in the last decades, and its diagnosis can be a challenge. Further and complementary testing based in biochemical alterations may be important to correctly identify thyroid cancer and prevent unnecessary surgery. Fourier-transform infrared (FTIR) spectroscopy is a metabolomic technique that has already shown promising results in cancer metabolome analysis of neoplastic thyroid tissue, in the identification and classification of prostate tumor tissues and of breast carcinoma, among others. This work aims to gather and discuss published information on the ability of FTIR spectroscopy to be used in metabolomic studies of the thyroid, including discriminating between benign and malignant thyroid samples and grading and classifying different types of thyroid tumors.
Non-Contact Optical Detection of Foreign Materials Adhered to Color Filter and Thin-Film Transistor
Authors: Tzu Fu-Ming , Hsu Shih-Hsien , Chen Jung-Shun
Published: January 2022

This paper describes the non-contact optical detection of debris material that adheres to the substrates of color filters (CFs) and thin-film transistors (TFTs) by area charge-coupled devices (CCDs) and laser sensors. One of the optical detections is a side-view illumination by an area CCD that emits a coherency light to detect debris on the CF. In contrast to the height of the debris material, the image is acquired by transforming the geometric shape from a square to a circle. As a result, the side-view illumination from the area CCD identified the height of the debris adhered to the black matrix (BM) as well as the red, green, and blue of a CF with 95, 97, 98, and 99% accuracy compared to the golden sample. The uncertainty analysis was at 5% for the BM, 3% for the red, 2% for the green, and 1% for the blue. The other optical detection, a laser optical interception with a horizontal alignment, inspected the material foreign to the TFT. At the same time, laser sensors intercepted the debris on the TFT at a voltage of 3.5 V, which the five sets of laser optics make scanning the sample. Consequently, the scanning rate reached over 98% accuracy, and the uncertainty analysis was within 5%. Thus, both non-contact optical methods can detect debris at a 50 μm height or lower. The experiment presents a successful design for the efficient prevention of a valuable component malfunction.
Comparison of the In Vitro and In Vivo Electrochemical Performance of Bionic Electrodes
Authors: Harris Alexander R. , Newbold Carrie , Stathopoulos Dimitra , Carter Paul , Cowan Robert , Wallace Gordon G.
Published: January 2022

The electrochemical performance of platinum electrodes was assessed in vitro and in vivo to determine the impact of electrode implantation and the relevance of in vitro testing in predicting in vivo behaviour. A significant change in electrochemical response was seen after electrode polarisation. As a result, initial in vitro measurements were poor predictors of subsequent measurements performed in vitro or in vivo. Charge storage capacity and charge density measurements from initial voltammetric measurements were not correlated with subsequent measurements. Electrode implantation also affected the electrochemical impedance. The typically reported impedance at 1 kHz was a very poor predictor of electrode performance. Lower frequencies were significantly more dependent on electrode properties, while higher frequencies were dependent on solution properties. Stronger correlations in impedance at low frequencies were seen between in vitro and in vivo measurements after electrode activation had occurred. Implanting the electrode increased the resistance of the electrochemical circuit, with bone having a higher resistivity than soft tissue. In contrast, protein fouling and fibrous tissue formation had a minimal impact on electrochemical response. In vivo electrochemical measurements also typically use a quasi-reference electrode, may operate in a 2-electrode system, and suffer from uncompensated resistance. The impact of these experimental conditions on electrochemical performance and the relevance of in vitro electrode assessment is discussed. Recommended in vitro testing protocols for assessing bionic electrodes are presented.
Figure of Merit Enhancement of Laterally Vibrating RF-MEMS Resonators via Energy-Preserving Addendum Frame
Authors: Workie Temesgen Bailie , Wu Zhaohui , Tang Panliang , Bao Jingfu , Hashimoto Ken-ya
Published: January 2022

This paper examines a new technique to improve the figure of merit of laterally vibrating RF-MEMS resonators through an energy-preserving suspended addendum frame structure using finite element analysis. The proposed suspended addendum frame on the sides of the resonant plate helps as a mechanical vibration isolator from the supporting substrate. This enables the resonator to have a low acoustic energy loss, resulting in a higher quality factor. The simulated attenuation characteristics of the suspended addendum frame are up to an order of magnitude larger than those achieved with the conventional structure. Even though the deployed technique does not have a significant impact on increasing the effective electromechanical coupling coefficient, due to a gigantic improvement in the unloaded quality factor, from 4106 to 51,136, the resonator with the suspended frame achieved an 11-folds improvement in the figure of merit compared to that of the conventional resonator. Moreover, the insertion loss was improved from 5 dB down to a value as low as 0.7 dB. Furthermore, a method of suppressing spurious mode is demonstrated to remove the one incurred by the reflected waves due to the proposed energy-preserving structure.
Synergistic In Vitro Antimicrobial Activity of Triton X-100 and Metformin against Enterococcus faecalis in Normal and High-Glucose Conditions
Authors: He Xinling , Jin Siqi , Fan Wei , Fan Bing
Published: January 2022

The prevention and treatment of oral diseases is more difficult in diabetic patients with poorly controlled blood glucose levels. This study aims to explore an effective, low-cytotoxicity medication for root canal treatment in diabetic patients. The antibacterial effect of the combination of Triton X-100 (TX-100) and metformin (Met) on Enterococcus faecalis (E. faecalis) was evaluated by determining the minimum inhibitory concentration (MIC), minimum bactericidal concentration required to kill 99% bacteria (MBC99) and by conducting dynamic time-killing assays. While the antibiofilm activity was measured by crystal violet (CV) assay, field emission scanning electron microscope (FE-SEM), confocal laser scanning microscope (CLSM) and colony-forming unit (CFU) counting assays. The expression of relative genes was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR), and the cytotoxicity of the new combination on MC3T3-E1 cell was also tested. Results showed that the antibacterial and antibiofilm activities of Met could be significantly enhanced by very low concentrations of TX-100 in both normal and high-glucose conditions, with a much lower cytotoxicity than 2% chlorhexidine (CHX). Thus, the TX-100 + Met combination may be developed as a promising and effective root canal disinfectant for patients with diabetes.
PCV13 Vaccination of Adults against Pneumococcal Disease: What We Have Learned from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA)
Authors: Theilacker Christian , Fletcher Mark , Jodar Luis , Gessner Bradford
Published: January 2022

The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA) evaluated older adult pneumococcal vaccination and was one of the largest vaccine clinical trials ever conducted. Among older adults aged ≥65 years, the trial established 13-valent pneumococcal conjugate vaccine (PCV13) efficacy in preventing first episodes of bacteremic and nonbacteremic pneumococcal vaccine serotype (VT) community acquired pneumonia (CAP), and of vaccine serotype invasive pneumococcal disease (VT-IPD). Since the publication of the original trial results, 15 additional publications have extended the analyses. In this review, we summarize and integrate the full body of evidence generated by these studies, contextualize the results in light of their public health relevance, and discuss their implications for the assessment of current and future adult pneumococcal vaccination. This accumulating evidence has helped to better understand PCV13 efficacy, serotype-specific efficacy, efficacy in subgroups, the interpretation of immunogenicity data, and the public health value of adult PCV vaccination.
From Surface to Subsurface: Diversity, Composition, and Abundance of Sessile and Endolithic Bacterial, Archaeal, and Eukaryotic Communities in Sand, Clay and Rock Substrates in the Laurentians (Quebec, Canada)
Authors: Meyer Julia , Zakhary Sheri , Larocque Marie , Lazar Cassandre S.
Published: January 2022

Microbial communities play an important role in shallow terrestrial subsurface ecosystems. Most studies of this habitat have focused on planktonic communities that are found in the groundwater of aquifer systems and only target specific microbial groups. Therefore, a systematic understanding of the processes that govern the assembly of endolithic and sessile communities is still missing. This study aims to understand the effect of depth and biotic factors on these communities, to better unravel their origins and to compare their composition with the communities detected in groundwater. To do so, we collected samples from two profiles (~0–50 m) in aquifer sites in the Laurentians (Quebec, Canada), performed DNA extractions and Illumina sequencing. The results suggest that changes in geological material characteristics with depth represent a strong ecological and phylogenetical filter for most archaeal and bacterial communities. Additionally, the vertical movement of water from the surface plays a major role in shallow subsurface microbial assembly processes. Furthermore, biotic interactions between bacteria and eukaryotes were mostly positive which may indicate cooperative or mutualistic potential associations, such as cross-feeding and/or syntrophic relationships in the terrestrial subsurface. Our results also point toward the importance of sampling both the geological formation and groundwater when it comes to studying its overall microbiology.
Double Mutations in Succinate Dehydrogenase Are Involved in SDHI Resistance in Corynespora cassiicola
Authors: Sun Bingxue , Zhu Guangxue , Xie Xuewen , Chai Ali , Li Lei , Shi Yanxia , Li Baoju
Published: January 2022

With the further application of succinate dehydrogenase inhibitors (SDHI), the resistance caused by double mutations in target gene is gradually becoming a serious problem, leading to a decrease of control efficacy. It is important to assess the sensitivity and fitness of double mutations to SDHI in Corynespora cassiicola and analysis the evolution of double mutations. We confirmed, by site-directed mutagenesis, that all double mutations (B-I280V+D-D95E/D-G109V/D-H105R, B-H278R+D-D95E/D-G109V, B-H278Y+D-D95E/D-G109V) conferred resistance to all SDHI and exhibited the increased resistance to at least one fungicide than single point mutation. Analyses of fitness showed that all double mutations had lower fitness than the wild type; most of double mutations suffered more fitness penalties than the corresponding single mutants. We also further found that double mutations (B-I280V+D-D95E/D-G109V/D-H105R) containing low SDHI-resistant single point mutation (B-I280V) exhibited higher resistance to SDHI and low fitness penalty than double mutations (B-H278Y+D-D95E/D-G109V) containing high SDHI-resistant single mutations (B-H278Y). Therefore, we may infer that a single mutation conferring low resistance is more likely to evolve into a double mutation conferring higher resistance under the selective pressure of SDHI. Taken together, our results provide some important reference for resistance management.
Whitlockite-Type Structure as a Matrix for Optical Materials: Synthesis and Characterization of Novel TM-SM Co-Doped Phosphate Ca9Gd(PO4)7, a Single-Phase White Light Phosphors
Authors: Nikiforov Ivan V. , Deyneko Dina V. , Spassky Dmitry A. , Lazoryak Bogdan I. , Aksenov Sergey M.
Published: January 2022

A series of novel phosphates with the general formulas Ca9Gd0.9−xTm0.1Smx(PO4)7 and Ca9Gd0.9−yTmySm0.1(PO4)7 were synthesized by solid-state method. As-obtained phosphates were characterized by powder X-ray diffraction and second harmonic generation analyses, dielectric measurements, luminescence spectroscopy. All samples were single phase and characterized by the whitlockite-type structure with space group R3c. An influence of admixture concentration of REE3+ ions in the initial host on dielectric properties was studied in details. Synthesized phosphates are characterized by intensive luminescence. The emission in the orange region of the visible spectrum is observed for Ca9Gd0.9Sm0.1(PO4)7 with a maximum intensity band at 602 nm. The line in blue region at 455 nm, which corresponds to 1D2 → 3F4 Tm3+ transition, is registered for Ca9Gd0.9Tm0.1(PO4)7. Emission in the white region of CIE coordinates was registered for Tm-Sm co-doped compounds.
Analytical and Chemometric Characterization of Fino and Amontillado Sherries during Aging in Criaderas y Solera System
Authors: Valcárcel-Muñoz Manuel J. , Guerrero-Chanivet María , Rodríguez-Dodero María del Carmen , García-Moreno María de Valme , Guillén-Sánchez Dominico A.
Published: January 2022

Fino and Amontillado are Sherry wines, produced in Marco de Jerez area (southern Spain), and aged in Criaderas y Solera system. Fino Sherry wine follows a biological aging process, under a veil of flor yeasts, while Amontillado Sherry wine shares the same biological aging firstly, followed by oxidative aging, which gives them special features. Organic acids, esters, higher alcohols, phenolic compounds and total dry extract of Sherries evolve during aging due to evaporation processes, physical-chemical reactions, wood contributions and microbiological activity. During aging, Sherry wines improve their organoleptic profile, as could be proved in the tasting sessions. Hierarchical Cluster Analysis and Factor Analysis with factor extraction using Principal Components of Sherry wines studied were carried out and natural groupings of the wines according to the type of aging and their age were observed. A strong correlation between the parameters analyzed and the aging of each wine has been seen in the Multiple Linear Regression studies, establishing two different models, one for each type of Sherry wine, that, with only four of all the variables studied estimated the wine age with more than 99% of confidence. This constitutes a useful tool to control the age of these Sherry wines in the winery.
A New Oxygen Containing Pyclen-Type Ligand as a Manganese(II) Binder for MRI and 52Mn PET Applications: Equilibrium, Kinetic, Relaxometric, Structural and Radiochemical Studies
Authors: Csupász Tibor , Szücs Dániel , Kálmán Ferenc Krisztián , Hollóczki Oldamur , Fekete Anikó , Szikra Dezső , Tóth Éva , Tóth Imre , Tircsó Gyula
Published: January 2022

A new pyclen-3,9-diacetate derivative ligand (H23,9-OPC2A) was synthesized possessing an etheric O-atom opposite to the pyridine ring, to improve the dissociation kinetics of its Mn(II) complex (pyclen = 3,6,9,15-tetraazabicyclo(9.3.1)pentadeca-1(15),11,13-triene). The new ligand is less basic than the N-containing analogue (H23,9-PC2A) due to the non-protonable O-atom. In spite of its lower basicity, the conditional stability of the [Mn(3,9-OPC2A)] (pMn = −log(Mn(II)), cL = cMn(II) = 0.01 mM. pH = 7.4) remains unaffected (pMn = 8.69), compared to the [Mn(3,9-PC2A)] (pMn = 8.64). The [Mn(3,9-OPC2A)] possesses one water molecule, having a lower exchange rate with bulk solvents (kex298 = 5.3 ± 0.4 × 107 s−1) than [Mn(3,9-PC2A)] (kex298 = 1.26 × 108 s−1). These mild differences are rationalized by density-functional theory (DFT) calculations. The acid assisted dissociation of [Mn(3,9-OPC2A)] is considerably slower (k1 = 2.81 ± 0.07 M−1 s−1) than that of the complexes of diacetates or bisamides of various 12-membered macrocycles and the parent H23,9-PC2A. The [Mn(3,9-OPC2A)] is inert in rat/human serum as confirmed by 52Mn labeling (nM range), as well as by relaxometry (mM range). However, a 600-fold excess of EDTA (pH = 7.4) or a mixture of essential metal ions, propagated some transchelation/transmetalation in 7 days. The H23,9-OPC2A is labeled efficiently with 52Mn at elevated temperatures, yet at 37 °C the parent H23,9-PC2A performs slightly better. Ultimately, the H23,9-OPC2A shows advantageous features for further ligand designs for bifunctional chelators.
Naringenin Induces ROS-Mediated ER Stress, Autophagy, and Apoptosis in Human Osteosarcoma Cell Lines
Authors: Lee Chiang-Wen , Huang Cathy Chia-Yu , Chi Miao-Ching , Lee Kuan-Han , Peng Kuo-Ti , Fang Mei-Ling , Chiang Yao-Chang , Liu Ju-Fang
Published: January 2022

Osteosarcoma, a primary bone tumor, responds poorly to chemotherapy and radiation therapy in children and young adults; hence, as the basis for an alternative treatment, this study investigated the cytotoxic and antiproliferative effects of naringenin on osteosarcoma cell lines, HOS and U2OS, by using cell counting kit-8 and colony formation assays. DNA fragmentation and the increase in the G2/M phase in HOS and U2OS cells upon treatment with various naringenin concentrations were determined by using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and Annexin V/propidium iodide double staining, respectively. Flow cytometry was performed, and 2′,7′-dichlorodihydrofluorescein diacetate, JC-1, and Fluo-4 AM ester probes were examined for reactive oxygen species (ROS) generation, mitochondrial membrane potential, and intracellular calcium levels, respectively. Caspase activation, cell cycle, cytosolic and mitochondrial, and autophagy-related proteins were determined using western blotting. The results indicated that naringenin significantly inhibited viability and proliferation of osteosarcoma cells in a dose-dependent manner. In addition, naringenin induced cell cycle arrest in osteosarcoma cells by inhibiting cyclin B1 and cyclin-dependent kinase 1 expression and upregulating p21 expression. Furthermore, naringenin significantly inhibited the growth of osteosarcoma cells by increasing the intracellular ROS level. Naringenin induced endoplasmic reticulum (ER) stress-mediated apoptosis through the upregulation of ER stress markers, GRP78 and GRP94. Naringenin caused acidic vesicular organelle formation and increased autophagolysosomes, microtubule-associated protein-light chain 3-II protein levels, and autophagy. The findings suggest that the induction of cell apoptosis, cell cycle arrest, and autophagy by naringenin through mitochondrial dysfunction, ROS production, and ER stress signaling pathways contribute to the antiproliferative effect of naringenin on osteosarcoma cells.
Chemical Profile, Antimicrobial and Antioxidant Activity Assessment of the Crude Extract and Its Main Flavonoids from Tartary Buckwheat Sprouts
Authors: Zhong Lingyun , Lin Yuji , Wang Can , Niu Bei , Xu Ying , Zhao Gang , Zhao Jianglin
Published: January 2022

The purpose of this study was to investigate the major flavonoids content and bioactivities of Tartary buckwheat sprouts. The crude methanol extract (ME) of Tartary buckwheat sprouts was abundant in flavonoids, and six major flavonoids, including isoorientin, vitexin, isovitexin, rutin, quercetin, and kaemferol were successfully determined from the sprouts by the high-performance liquid chromatography (HPLC) method. Generally, the flavonoid content of buckwheat sprouts was in the order of rutin > quercetin > isovitexin > vitexin> isoorientin > kaemferol. The highest rutin content of the ME and sprout cultures was 89.81 mg/g and 31.50 mg/g, respectively. Antibacterial activity results indicated the ME displayed notable inhibitory activity against the five tested bacteria, and its minimum inhibitory concentration (MIC) values ranged from 0.8 mg/mL to 3.2 mg/mL. Among the six flavonoids, quercetin was the most active compound, which exhibited strong activity against all tested bacteria except for E. coli and S. epidermidis, with its MIC values ranging from 0.2 mg/mL to 0.4 mg/mL. For the antifungal activity assay, the ME of Tartary buckwheat sprouts and four flavonoids could significantly inhibit the spore germination of two pathogenic fungi, and their inhibitory efficiency was concentration dependent. Quercetin was the most active one, which significantly inhibited the spore germination of F. oxysporum f. sp. vasinfectum and F. oxysporum f. sp. cucumerinum, and its median effective inhibitory concentration (IC50) value was 42.36 and 32.85 µg/mL, respectively. The antioxidant activity results showed that quercetin, kaemferol, and rutin displayed excellent antioxidant activity in the DPPH radical scavenging test, and their IC50 value was calculated as 5.60, 16.23, and 27.95 µg/mL, respectively. This is the first report on the antimicrobial activity of the crude extract of Tartary buckwheat sprouts. These results indicated that the methanol extract of Tartary buckwheat sprouts could be used as a potential antimicrobial or antioxidant agent in the future.
Structural Identification of Metalloproteomes in Marine Diatoms, an Efficient Algae Model in Toxic Metals Bioremediation
Authors: Chasapis Christos T. , Peana Massimiliano , Bekiari Vlasoula
Published: January 2022

The biosorption of pollutants using microbial organisms has received growing interest in the last decades. Diatoms, the most dominant group of phytoplankton in oceans, are (i) pollution tolerant species, (ii) excellent biological indicators of water quality, and (iii) efficient models in assimilation and detoxification of toxic metal ions. Published research articles connecting proteomics with the capacity of diatoms for toxic metal removal are very limited. In this work, we employed a structural based systematic approach to predict and analyze the metalloproteome of six species of marine diatoms: Thalassiosira pseudonana, Phaeodactylum tricornutum, Fragilariopsis cylindrus, Thalassiosira oceanica, Fistulifera solaris, and Pseudo-nitzschia multistriata. The results indicate that the metalloproteome constitutes a significant proportion (~13%) of the total diatom proteome for all species investigated, and the proteins binding non-essential metals (Cd, Hg, Pb, Cr, As, and Ba) are significantly more than those identified for essential metals (Zn, Cu, Fe, Ca, Mg, Mn, Co, and Ni). These findings are most likely related to the well-known toxic metal tolerance of diatoms. In this study, metalloproteomes that may be involved in metabolic processes and in the mechanisms of bioaccumulation and detoxification of toxic metals of diatoms after exposure to toxic metals were identified and described.
Unveiling of Pyrimidindinones as Potential Anti-Norovirus Agents—A Pharmacoinformatic-Based Approach
Authors: Ebenezer Oluwakemi , Damoyi Nkululeko , Jordaan Maryam A. , Shapi Michael
Published: January 2022

The RNA-dependent RNA polymerase (RdRp) receptor is an attractive target for treating human norovirus (HNV). A computer-aided approach like e-pharmacophore, molecular docking, and single point energy calculations were performed on the compounds retrieved from the Development Therapeutics Program (DTP) AIDS Antiviral Screen Database to identify the antiviral agent that could target the HNV RdRp receptor. Induced-fit docking (IFD) results showed that compounds ZINC1617939, ZINC1642549, ZINC6425208, ZINC5887658 and ZINC32068149 bind with the residues in the active site-B of HNV RdRp receptor via hydrogen bonds, salt bridge, and electrostatic interactions. During the molecular dynamic simulations, compounds ZINC6425208, ZINC5887658 and ZINC32068149 displayed an unbalanced backbone conformation with HNV RdRp protein, while ZINC1617939 and ZINC1642549 maintained stability with the protein backbone when interacting with the residues. Hence, the two new concluding compounds discovered by the computational approach can be used as a chemotype to design promising antiviral agents aimed at HNV RdRp.
Droplet Flow Assisted Electrocatalytic Oxidation of Selected Alcohols under Ambient Condition
Authors: Suliman Mohammed A. , Al Aqad Khaled M. , Basheer Chanbasha
Published: January 2022

This study reports using a droplet flow assisted mechanism to enhance the electrocatalytic oxidation of benzyl alcohol, 2-phenoxyethanol, and hydroxymethylfurfural at room temperature. Cobalt phosphide (CoP) was employed as an active electrocatalyst to promote the oxidation of each of the individual substrates. Surface analysis of the CoP electrocatalyst using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), as well as electrochemical characterization, revealed that it had excellent catalytic activity for each of the substrates studied. The combined droplet flow with the continuous flow electrochemical oxidation approach significantly enhanced the conversion and selectivity of the transformation reactions. The results of this investigation show that at an electrolysis potential of 1.3 V and ambient conditions, both the selectivity and yield of aldehyde from substrate conversion can reach 97.0%.
Insecticide, Acaricide, Repellent and Antimicrobial Development
Authors: Benelli Giovanni
Published: January 2022

The quick spread of invasive arthropod species worldwide, sometimes boosted by global warming and urbanization [...]