bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Surrogate Endpoints Using Information-Theoretic Measure of Association Based on Havrda and Charvat Entropy
Authors: Pardo María del Carmen , Zhao Qian , Jin Hua , Lu Ying
Published: January 2022

Surrogate endpoints have been used to assess the efficacy of a treatment and can potentially reduce the duration and/or number of required patients for clinical trials. Using information theory, Alonso et al. (2007) proposed a unified framework based on Shannon entropy, a new definition of surrogacy that departed from the hypothesis testing framework. In this paper, a new family of surrogacy measures under Havrda and Charvat (H-C) entropy is derived which contains Alonso’s definition as a particular case. Furthermore, we extend our approach to a new model based on the information-theoretic measure of association for a longitudinally collected continuous surrogate endpoint for a binary clinical endpoint of a clinical trial using H-C entropy. The new model is illustrated through the analysis of data from a completed clinical trial. It demonstrates advantages of H-C entropy-based surrogacy measures in the evaluation of scheduling longitudinal biomarker visits for a phase 2 randomized controlled clinical trial for treatment of multiple sclerosis.
Gulf Countries’ Citizens’ Acceptance of COVID-19 Vaccines—A Machine Learning Approach
Authors: Alabrah Amerah , Alawadh Husam M. , Okon Ofonime Dominic , Meraj Talha , Rauf Hafiz Tayyab
Published: January 2022

The COVID-19 pandemic created a global emergency in many sectors. The spread of the disease can be subdued through timely vaccination. The COVID-19 vaccination process in various countries is ongoing and is slowing down due to multiple factors. Many studies on European countries and the USA have been conducted and have highlighted the public’s concern that over-vaccination results in slowing the vaccination rate. Similarly, we analyzed a collection of data from the gulf countries’ citizens’ COVID-19 vaccine-related discourse shared on social media websites, mainly via Twitter. The people’s feedback regarding different types of vaccines needs to be considered to increase the vaccination process. In this paper, the concerns of Gulf countries’ people are highlighted to lessen the vaccine hesitancy. The proposed approach emphasizes the Gulf region-specific concerns related to COVID-19 vaccination accurately using machine learning (ML)-based methods. The collected data were filtered and tokenized to analyze the sentiments extracted using three different methods: Ratio, TextBlob, and VADER methods. The sentiment-scored data were classified into positive and negative tweeted data using a proposed LSTM method. Subsequently, to obtain more confidence in classification, the in-depth features from the proposed LSTM were extracted and given to four different ML classifiers. The ratio, TextBlob, and VADER sentiment scores were separately provided to LSTM and four machine learning classifiers. The VADER sentiment scores had the best classification results using fine-KNN and Ensemble boost with 94.01% classification accuracy. Given the improved accuracy, the proposed scheme is robust and confident in classifying and determining sentiments in Twitter discourse.
Post-Quantum Chebyshev-Type Integral Inequalities for Synchronous Functions
Authors: Arunrat Nuttapong , Nakprasit Keaitsuda Maneeruk , Nonlaopon Kamsing , Agarwal Praveen , Ntouyas Sotiris K.
Published: January 2022

In this paper, we apply (p,q)-calculus to establish some new Chebyshev-type integral inequalities for synchronous functions. In particular, we generalize results of quantum Chebyshev-type integral inequalities by using (p,q)-integral. By taking p=1 and q→1, our results reduce to classical results on Chebyshev-type inequalities for synchronous functions. Furthermore, we consider their relevance with other related known results.
Effect of a Novel Tooth Pitting Model on Mesh Stiffness and Vibration Response of Spur Gears
Authors: Hou Jingyu , Yang Shaopu , Li Qiang , Liu Yongqiang
Published: January 2022

The existence of pitting failure has a direct influence on the time-varying mesh stiffness (TVMS) and thus changes the vibration properties of the gears. The shape of pitting on the tooth surface is characterized by randomness and geometric complexity. The overlapping pitting shape has rarely been investigated, especially when the misalignment of gear base circle and root circle was considered. In this paper, the pitting shape is considered as approximately the union of several ellipse cylinders, in which the gear tooth is treated as a cantilever beam starting from the root circle. Then, the TVMS of perfect gear and that of gear with different pitting severity levels are solved by the potential energy method. The effect of pitting size on TVMS is discussed in detail. In addition, the vibration response in the frequency domain for the gear system is analyzed, and the effectiveness is qualitatively verified by comparing with the vibration signals of the experimental gearbox. The results indicate that the new pitting model overcomes the problem of ignoring the overlap between different pits and is more consistent with the actual situation. The presence of tooth pitting reduces the TVMS, and the complex sidebands appear around the gear mesh frequency and its harmonics. The proposed model can be used to predict the fluctuation of gear mesh stiffness when tooth pitting occurs, and the corresponding dynamic characteristics can provide the theoretical basis for gear condition monitoring and fault diagnosis.
Thin Film Biocomposite Membrane for Forward Osmosis Supported by Eggshell Membrane
Authors: Kim Teayeop , Park Sunho , Lee Yoonkyung , Kim Jangho , Kim Kyunghoon
Published: January 2022

There is a general drive to adopt highly porous and less tortuous supports for forward osmosis (FO) membranes to reduce internal concentration polarization (ICP), which regulates the osmotic water permeation. As an abundant waste material, eggshell membrane (ESM) has a highly porous and fibrous structure that meets the requirements for FO membrane substrates. In this study, a polyamide-based biocomposite FO membrane was fabricated by exploiting ESM as a membrane support. The polyamide layer was deposited by the interfacial polymerization technique and the composite membrane exhibited osmotically driven water flux. Further, biocomposite FO membranes were developed by surface coating with GO for stable formation of the polyamide layer. Finally, the osmotic water flux of the eggshell composite membrane with a low structural parameter (~138 µm) reached 46.19 L m−2 h−1 in FO mode using 2 M NaCl draw solution.
Development of a Membrane Module Prototype for Oxygen Separation in Industrial Applications
Authors: Drago Francesca , Fedeli Paolo , Cavaliere Angelo , Cammi Andrea , Passoni Stefano , Mereu Riccardo , De La Pierre Stefano , Smeacetto Federico , Ferraris Monica
Published: January 2022

The integration of oxygen transport membranes in industrial processes can lead to energy and economic advantages, but proof of concept membrane modules are highly necessary to demonstrate the feasibility of this technology. In this work, we describe the development of a lab-scale module through a comprehensive study that takes into consideration all the relevant technological aspects to achieve a prototype ready to be operated in industrial environment. We employed scalable techniques to manufacture planar La0.6Sr0.4Co0.2Fe0.8O3-δ membrane components suitable for the application in both 3- and 4-end mode, designed with a geometry that guarantees a failure probability under real operating conditions as low as 2.2 × 10−6. The asymmetric membranes that act as separation layers showed a permeation of approx. 3 NmL/min/cm2 at 900 °C in air/He gradient, with a remarkable stability up to 720 h, and we used permeation results to develop a CFD model that describes the influence of the working conditions on the module performance. The housing of the membrane component is an Inconel 625 case joined to the membrane component by means of a custom-developed glass–ceramic sealant that exhibited a remarkable thermo-chemical compatibility both with metal and ceramic, despite the appearance of chemical strain in LSCF at high temperature. The multi-disciplinary approach followed in this work is suitable to be adapted to other module concepts based on membrane components with different dimensions, layouts or materials.
Membrane Bioreactor for Simultaneous Synthesis and Fractionation of Oligosaccharides
Authors: Botelho Vanessa A. , Mateus Marília , Petrus José C. C. , de Pinho Maria Norberta
Published: January 2022

Galacto-oligosaccharides (GOS) are prebiotic sugars obtained enzymatically from lactose and used in food industry due to their nutritional advantages or technological properties. Selective mass transport and enzymatic synthesis were integrated and followed using a membrane bioreactor, so that selective removal of reaction products may lead to increased conversions of product-inhibited or thermodynamically unfavorable reactions. GOS syntheses were conducted on lactose solutions (150 g·L−1) at 40 °C and 10 Uβ-galactosidase.mL−1, and sugar fractionation was performed by cellulose acetate membranes. Effects of pressure (20; 24 bar) and crossflow velocity (1.7; 2.0; 2.4 m·s−1) on bioreactor performance were studied. Simultaneous GOS synthesis and production fractionation increased GOS production by 60%, in comparison to the same reactions promoted without permeation. The presence of a high-molecular-weight solute, the enzyme, in association with high total sugar concentration, leads to complex selective mass transfer characteristics. Without the enzyme, the membrane presented tight ultrafiltration characteristics, permeating mono- and disaccharides and retaining just 25% of trisaccharides. During simultaneous synthesis and fractionation, GOS-3 were totally retained, and GOS-2 and monosaccharides were retained at 80% and 40%, respectively. GOS synthesis—hydrolysis evolution was strongly dependent on crossflow velocity at 20 bar but became fairly independent at 24 bar.
Al-Mn Intermetallics in High Pressure Die Cast AZ91 and Direct Chill Cast AZ80
Authors: Peng Liuqing , Zeng Guang , Wang Di , Xian Jingwei , Ji Shouxun , Zhan Hongyi , Gourlay Christopher M.
Published: January 2022

Manganese-bearing intermetallic compounds (IMCs) are important for ensuring adequate corrosion performance of magnesium-aluminium alloys and can be deleterious to mechanical performance if they are large and/or form clusters. Here, we explore the formation of Al-Mn IMCs in Mg-9Al-0.7Zn-0.2Mn produced by two industrial casting processes, high-pressure die casting (HPDC) and direct chill (DC) casting. As Al8Mn5 starts forming above the α-Mg liquidus temperature in this alloy, we consider its formation during melt handling as well as during casting and heat treatment. In HPDC, we focus on sludge formation in the holding pot, partial solidification of IMCs in the shot chamber, and Al-Mn IMC solidification in the die cavity. In DC casting, we focus on interactions between Al-Mn IMCs and oxide films in the launder system, Al-Mn IMC solidification in the billet, and the partial transformation of Al8Mn5 into Al11Mn4 during solution heat treatment. The results show that minimising pre-solidification in the shot sleeve of HPDC and controlling pouring and filtration in DC casting are important for ensuring small Al-Mn intermetallic particles in these casting processes.
A Potential Role for Bile Acid Signaling in Celiac Disease-Associated Fatty Liver
Authors: Manka Paul , Sydor Svenja , Schänzer-Ocklenburg Julia M. , Brandenburg Malte , Best Jan , Vilchez-Vargas Ramiro , Link Alexander , Heider Dominik , Brodesser Susanne , Figge Anja , Jähnert Andreas , Coombes Jason D. , Cubero Francisco Javier , Kahraman Alisan , Kim Moon-Sung , Kälsch Julia , Kinner Sonja , Faber Klaas Nico , Moshage Han , Gerken Guido , Syn Wing-Kin , Canbay Ali , Bechmann Lars P.
Published: January 2022

Celiac disease (CeD) is a chronic autoimmune disorder characterized by an intolerance to storage proteins of many grains. CeD is frequently associated with liver damage and steatosis. Bile acid (BA) signaling has been identified as an important mediator in gut–liver interaction and the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here, we aimed to analyze BA signaling and liver injury in CeD patients. Therefore, we analyzed data of 20 CeD patients on a gluten-free diet compared to 20 healthy controls (HC). We furthermore analyzed transaminase levels, markers of cell death, BA, and fatty acid metabolism. Hepatic steatosis was determined via transient elastography, by MRI and non-invasive scores. In CeD, we observed an increase of the apoptosis marker M30 and more hepatic steatosis as compared to HC. Fibroblast growth factor 19 (FGF19) was repressed in CeD, while low levels were associated with steatosis, especially in patients with high levels of anti-tissue transglutaminase antibodies (anti-tTG). When comparing anti-tTG-positive CeD patients to individuals without detectable anti-tTG levels, hepatic steatosis was accentuated. CeD patients with significant sonographic steatosis (defined by CAP ≥ 283 db/m) were exclusively anti-tTG-positive. In summary, our results suggest that even in CeD patients in clinical remission under gluten-free diet, alterations in gut–liver axis, especially BA signaling, might contribute to steatotic liver injury and should be further addressed in future studies and clinical practice.
Multispectral Imaging Flow Cytometry with Spatially and Spectrally Resolving Snapshot-Mosaic Cameras for the Characterization and Classification of Bioparticles
Authors: Dittrich Paul-Gerald , Kraus Daniel , Ehrhardt Enrico , Henkel Thomas , Notni Gunther
Published: January 2022

In the development and optimization of biotechnological cultivation processes the continuous monitoring through the acquisition and interpretation of spectral and morphological properties of bioparticles are challenging. There is therefore a need for the parallel acquisition and interpretation of spatially and spectrally resolved measurements with which particles can be characterized and classified in-flow with high throughput. Therefore, in this paper we investigated the scientific and technological connectivity of standard imaging flow cytometry (IFC) with filter-on-chip based spatially and spectrally resolving snapshot-mosaic cameras for photonic sensing and control in a smart and innovative microfluidic device. For the investigations presented here we used the microalgae Haematococcus pluvialis (HP). These microalgae are used commercially to produce the antioxidant keto-carotenoid astaxanthin. Therefore, HP is relevant to practically demonstrate the usability of the developed system for Multispectral Imaging Flow Cytometry (MIFC) platform. The extension of standard IFC with snapshot-mosaic cameras and multivariate data processing is an innovative approach for the in-flow characterization and derived classification of bioparticles. Finally, the multispectral data acquisition and the therefore developed methodology is generalizable and enables further applications far beyond the here characterized population of HP cells.
Neuraminidase Inhibitor of Garcinia atroviridis L. Fruits and Leaves Using Partial Purification and Molecular Characterization
Authors: Muchtaridi Muchtaridi , Nuwarda Rina Fajri , Ikram Emmy Hainida Khairul , Abdul Rahim Aisyah Saad , Gazzali Amirah Mohd , Wahab Habibah A.
Published: January 2022

Neuraminidase (NA) is an enzyme that prevents virions from aggregating within the host cell and promotes cell-to-cell spread by cleaving glycosidic linkages to sialic acid. The best-known neuraminidase is the viral neuraminidase, which present in the influenza virus. Thus, the development of anti-influenza drugs that inhibit NA has emerged as an important and intriguing approach in the treatment of influenza. Garcinia atroviridis L. (GA) dried fruits (GAF) are used commercially as seasoning and in beverages. The main objective of this study was to identify a new potential neuraminidase inhibitor from GA. A bioassay-guided fractionation method was applied to obtain the bioactive compounds leading to the identification of garcinia acid and naringenin. In an enzyme inhibition study, garcinia acid demonstrated the highest activity when compared to naringenin. Garcinia acid had the highest activity, with an IC50 of 17.34–17.53 µg/mL or 91.22–92.21 µM against Clostridium perfringens-NA, and 56.71–57.85 µg/mL or 298.32–304.31 µM against H1N1-NA. Based on molecular docking results, garcinia acid interacted with the triad arginine residues (Arg118, Arg292, and Arg371) of the viral neuraminidase, implying that this compound has the potential to act as a NA enzyme inhibitor.
Mechanistic Insight into Oxidative Stress-Triggered Signaling Pathways and Type 2 Diabetes
Authors: Singh Anju , Kukreti Ritushree , Saso Luciano , Kukreti Shrikant
Published: January 2022

Oxidative stress (OS) is a metabolic dysfunction mediated by the imbalance between the biochemical processes leading to elevated production of reactive oxygen species (ROS) and the antioxidant defense system of the body. It has a ubiquitous role in the development of numerous noncommunicable maladies including cardiovascular diseases, cancers, neurodegenerative diseases, aging and respiratory diseases. Diseases associated with metabolic dysfunction may be influenced by changes in the redox balance. Lately, there has been increasing awareness and evidence that diabetes mellitus (DM), particularly type 2 diabetes, is significantly modulated by oxidative stress. DM is a state of impaired metabolism characterized by hyperglycemia, resulting from defects in insulin secretion or action, or both. ROS such as hydrogen peroxide and the superoxide anion introduce chemical changes virtually in all cellular components, causing deleterious effects on the islets of β-cells, in turn affecting insulin production. Under hyperglycemic conditions, various signaling pathways such as nuclear factor-κβ (NF-κβ) and protein kinase C (PKC) are also activated by ROS. All of these can be linked to a hindrance in insulin signaling pathways, leading to insulin resistance. Hyperglycemia-induced oxidative stress plays a substantial role in complications including diabetic nephropathy. DM patients are more prone to microvascular as well as atherosclerotic macrovascular diseases. This systemic disease affects most countries around the world, owing to population explosion, aging, urbanization, obesity, lifestyle, etc. However, some modulators, with their free radical scavenging properties, can play a prospective role in overcoming the debilitating effects of OS. This review is a modest approach to summarizing the basics and interlinkages of oxidative stress, its modulators and diabetes mellitus. It may add to the understanding of and insight into the pathophysiology of diabetes and the crucial role of antioxidants to weaken the complications and morbidity resulting from this chronic disease.
Isolation and Characterization of Two Chalcone Derivatives with Anti-Hepatitis B Virus Activity from the Endemic Socotraen Dracaena cinnabari (Dragon’s Blood Tree)
Authors: Mothana Ramzi A. , Arbab Ahmed H. , ElGamal Ali A. , Parvez Mohammad K. , Al-Dosari Mohammed S.
Published: January 2022

Hepatitis B virus (HBV) infection is prevalent and continues to be a global health concern. In this study, we determined the anti-hepatitis B virus (HBV) potential of the Socotra-endemic medicinal plant Dracaena cinnabari and isolated and characterized the responsible constituents. A bioassay-guided fractionation using different chromatographic techniques of the methanolic extract of D. cinnabari led to the isolation of two chalcone derivatives. Using a variety of spectroscopic techniques, including 1H-, 13C-, and 2D-NMR, these derivatives were identified as 2,4’-dihydroxy-4-methoxydihydrochalcone (compound 1) and 2,4’-dihydroxy-4-methoxyhydrochalcone (compound 2). Both compounds were isolated for the first time from the red resin (dragon’s blood) of D. cinnabari. The compounds were first evaluated for cytotoxicity on HepG2.2.15 cells and 50% cytotoxicity concentration (CC50) values were determined. They were then evaluated for anti-HBV activity against HepG2.2.15 cells by assessing the suppression of HBsAg and HBeAg production in the culture supernatants and their half maximum inhibitory concentration (IC50) and therapeutic index (TI) values were determined. Compounds 1 and 2 indicated inhibition of HBsAg production in a dose- and time-dependent manner with IC50 values of 20.56 and 6.36 μg/mL, respectively.
Catalytic Transformation of Triglycerides to Biodiesel with SiO2-SO3H and Quaternary Ammonium Salts in Toluene or DMSO
Authors: Barbosa Sandro L. , Rocha Adeline C. Pereira , Nelson David Lee , de Freitas Milton S. , Mestre Antônio A. P. Fulgêncio , Klein Stanlei I. , Clososki Giuliano C. , Caires Franco J. , Flumignan Danilo L. , dos Santos Letícia Karen , Wentz Alexandre P. , Pasa Vânya M. Duarte , Rios Regiane D. Fernandes
Published: January 2022

SiO2-SO3H, with a surface area of 115 m2·g−1, pore volumes of 0.38 cm3·g−1 and 1.32 mmol H+/g, was used as a transesterification catalyst. Triglycerides of waste cooking oil reacted with methanol in refluxing toluene to yield mixtures of diglycerides, monoglycerides and fatty acid methyl esters (FAMEs) in the presence of 20% (w/w) catalyst/oil using the hydrophilic sulfonated silica (SiO2-SO3H) catalyst alone or with the addition of 10% (w/w) co-catalyst/oil [(Bun4N)(BF4) or Aliquat 336]. The addition of the ammonium salts to the catalyst lead to a decrease in the amounts of diglycerides in the products, but the concentrations of monoglycerides increased. Mixtures of (Bun4N)(BF4)/catalyst were superior to catalyst alone or Aliquat 336/catalyst for promoting the production of mixtures with high concentrations of FAMEs. The same experiments were repeated using DMSO as the solvent. The use of the more polar solvent resulted in excellent conversion of the triglycerides to FAME esters with all three-catalyst media. A simplified mechanism is presented to account for the experimental results.
Effectively Converting Cane Molasses into 2,3-Butanediol Using Clostridiumljungdahlii by an Integrated Fermentation and Membrane Separation Process
Authors: Yang Yuling , Deng Tingting , Cao Weifeng , Shen Fei , Liu Sijia , Zhang Jing , Liang Xinquan , Wan Yinhua
Published: January 2022

Firstly, 2,3-butanediol (2,3-BDO) is a chemical platform used in several applications. However, the pathogenic nature of its producers and the expensive feedstocks used limit its scale production. In this study, cane molasses was used for 2,3-BDO production by a nonpathogenic Clostridium ljungdahlii. It was found that cane molasses alone, without the addition of other ingredients, was favorable for use as the culture medium for 2,3-BDO production. Compared with the control (i.e., the modified DSMZ 879 medium), the differential genes are mainly involved in the pathways of carbohydrate metabolism, membrane transport, and amino acid metabolism in the case of the cane molasses alone. However, when cane molasses alone was used, cell growth was significantly inhibited by KCl in cane molasses. Similarly, a high concentration of sugars (i.e., above 35 g/L) can inhibit cell growth and 2,3-BDO production. More seriously, 2,3-BDO production was inhibited by itself. As a result, cane molasses alone with an initial 35 g/L total sugars was suitable for 2,3-BDO production in batch culture. Finally, an integrated fermentation and membrane separation process was developed to maintain high 2,3-BDO productivity of 0.46 g·L−1·h−1. Meanwhile, the varied fouling mechanism indicated that the fermentation properties changed significantly, especially for the cell properties. Therefore, the integrated fermentation and membrane separation process was favorable for 2,3-BDO production by C. ljungdahlii using cane molasses.
A New Series of Aryloxyacetic Acids Endowed with Multi-Target Activity towards Peroxisome Proliferator-Activated Receptors (PPARs), Fatty Acid Amide Hydrolase (FAAH), and Acetylcholinesterase (AChE)
Authors: Leuci Rosalba , Brunetti Leonardo , Laghezza Antonio , Piemontese Luca , Carrieri Antonio , Pisani Leonardo , Tortorella Paolo , Catto Marco , Loiodice Fulvio
Published: January 2022

A new series of aryloxyacetic acids was prepared and tested as peroxisome proliferator-activated receptors (PPARs) agonists and fatty acid amide hydrolase (FAAH) inhibitors. Some compounds exhibited an interesting dual activity that has been recently proposed as a new potential therapeutic strategy for the treatment of Alzheimer’s disease (AD). AD is a multifactorial pathology, hence multi-target agents are currently one of the main lines of research for the therapy and prevention of this disease. Given that cholinesterases represent one of the most common targets of recent research, we decided to also evaluate the effects of our compounds on the inhibition of these specific enzymes. Interestingly, two of these compounds, (S)-5 and 6, showed moderate activity against acetylcholinesterase (AChE) and even some activity, although at high concentration, against Aβ peptide aggregation, thus demonstrating, in agreement with the preliminary dockings carried out on the different targets, the feasibility of a simultaneous multi-target activity towards PPARs, FAAH, and AChE. As far as we know, these are the first examples of molecules endowed with this pharmacological profile that might represent a promising line of research for the identification of novel candidates for the treatment of AD.
Pentacyclic Triterpenoids Isolated from Celastraceae: A Focus in the 13C-NMR Data
Authors: Camargo Karen Caroline , de Aguilar Mariana Guerra , Moraes Acácio Raphael Aguiar , de Castro Raquel Goes , Szczerbowski Daiane , Miguel Elizabeth Luciana Marinho , Oliveira Leila Renan , Sousa Grasiely Faria , Vidal Diogo Montes , Duarte Lucienir Pains
Published: January 2022

The Celastraceae family comprises about 96 genera and more than 1.350 species, occurring mainly in tropical and subtropical regions of the world. The species of this family stand out as important plant sources of triterpenes, both in terms of abundance and structural diversity. Triterpenoids found in Celastraceae species display mainly lupane, ursane, oleanane, and friedelane skeletons, exhibiting a wide range of biological activities such as antiviral, antimicrobial, analgesic, anti-inflammatory, and cytotoxic against various tumor cell lines. This review aimed to document all triterpenes isolated from different botanical parts of species of the Celastraceae family covering 2001 to 2021. Furthermore, a compilation of their 13C-NMR data was carried out to help characterize compounds in future investigations. A total of 504 pentacyclic triterpenes were compiled and distinguished as 29 aromatic, 50 dimers, 103 friedelanes, 89 lupanes, 102 oleananes, 22 quinonemethides, 88 ursanes and 21 classified as others.
Inhibition of Glutamate Release from Rat Cortical Nerve Terminals by Dehydrocorydaline, an Alkaloid from Corydalis yanhusuo
Authors: Lin Tzu-Yu , Chen I-Yen , Lee Ming-Yi , Lu Cheng-Wei , Chiu Kuan-Ming , Wang Su-Jane
Published: January 2022

Excessive release of glutamate induces excitotoxicity and causes neuronal damage in several neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for preventing and treating neurological disorders. Dehydrocorydaline (DHC), an active alkaloid compound isolated from Corydalis yanhusuo, possesses neuroprotective capacity. The present study investigated the effect of DHC on glutamate release using a rat brain cortical synaptosome model. Our results indicate that DHC inhibited 4-aminopyridine (4-AP)-evoked glutamate release and elevated intrasynaptosomal calcium levels. The inhibitory effect of DHC on 4-AP-evoked glutamate release was prevented in the presence of the vesicular transporter inhibitor bafilomycin A1 and the N- and P/Q-type Ca2+ channel blocker ω-conotoxin MVIIC but not the intracellular inhibitor of Ca2+ release dantrolene or the mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157. Moreover, the inhibitory effect of DHC on evoked glutamate release was prevented by the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) inhibitor PD98059. Western blotting data in synaptosomes also showed that DHC significantly decreased the level of ERK1/2 phosphorylation and synaptic vesicle-associated protein synapsin I, the main presynaptic target of ERK. Together, these results suggest that DHC inhibits presynaptic glutamate release from cerebrocortical synaptosomes by suppressing presynaptic voltage-dependent Ca2+ entry and the MAPK/ERK/synapsin I signaling pathway.
A Molecular-Wide and Electron Density-Based Approach in Exploring Chemical Reactivity and Explicit Dimethyl Sulfoxide (DMSO) Solvent Molecule Effects in the Proline Catalyzed Aldol Reaction
Authors: Cukrowski Ignacy , Dhimba George , Riley Darren L.
Published: January 2022

Modelling of the proline (1) catalyzed aldol reaction (with acetone 2) in the presence of an explicit molecule of dimethyl sulfoxide (DMSO) (3) has showed that 3 is a major player in the aldol reaction as it plays a double role. Through strong interactions with 1 and acetone 2, it leads to a significant increase of energy barriers at transition states (TS) for the lowest energy conformer 1a of proline. Just the opposite holds for the higher energy conformer 1b. Both the ‘inhibitor’ and ‘catalyst’ mode of activity of DMSO eliminates 1a as a catalyst at the very beginning of the process and promotes the chemical reactivity, hence catalytic ability of 1b. Modelling using a Molecular-Wide and Electron Density-based concept of Chemical Bonding (MOWED-CB) and the Reaction Energy Profile–Fragment Attributed Molecular System Energy Change (REP-FAMSEC) protocol has shown that, due to strong intermolecular interactions, the HN-C-COOH (of 1), CO (of 2), and SO (of 3) fragments drive a chemical change throughout the catalytic reaction. We strongly advocate exploring the pre-organization of molecules from initially formed complexes, through local minima to the best structures suited for a catalytic process. In this regard, a unique combination of MOWED-CB with REP-FAMSEC provides an invaluable insight on the potential success of a catalytic process, or reaction mechanism in general. The protocol reported herein is suitable for explaining classical reaction energy profiles computed for many synthetic processes.
Myokines in Appetite Control and Energy Balance
Authors: Grannell Andrew , Kokkinos Alexander , le Roux Carel W.
Published: January 2022

Efficacy of obesity treatments varies between individuals, highlighting the presence of responders and non-responders. Whilst exercise alone or exercise combined with diet leads to underwhelming weight loss for most, there exist super responders losing significant weight. Furthermore, in response to weight loss, the majority but not all patients tend to regain weight. Within the biopsychosocial model, biology as a determinant of response has been underappreciated. The understanding of the role that organs beyond adipose tissue and the gastrointestinal tract play in appetite control and body weight regulation has developed in recent years. The aim of this review is to highlight potential myokines that may be important in appetite physiology and overall energy balance. A number of attractive targets are described that warrant further investigation. A deeper understanding of how these myokines may drive feeding behaviours has the potential to improve measures to prevent and treat obesity through a precision medicine approach.
A Systematic Review of Psychobiotic Interventions in Children and Adolescents to Enhance Cognitive Functioning and Emotional Behavior
Authors: Basso Melissa , Johnstone Nicola , Knytl Paul , Nauta Arjen , Groeneveld Andre , Cohen Kadosh Kathrin
Published: January 2022

This systematic review brings together human psychobiotic interventions in children and adolescents (aged 6–25 years) to evaluate the efficacy of pre- and probiotic supplements on stress, anxiety, and cognitive outcomes. Psychobiotic interventions in animal studies highlighted sensitivity to effects during development and maturation in multiple domains from emotion to cognitive processing. Several translational psychobiotic interventions in humans have been carried out to assess effects on emotion and cognition during childhood and into adulthood. The findings illustrate that there are limited consistent psychobiotic effects in developing human populations, and this is proposed to be due to heterogeneity in the trials conducted. Consequentially, it is recommended that three specific factors are considered in future psychobiotic trials: (1) Specificity of population studied (e.g., patients, developmental age), (2) specificity of intervention, and (3) homogeneity in outcome measures.
Incremental Costs and Diners’ Satisfaction Associated with Improvement in Nutritional Value of Catering Dishes
Authors: Katz-Shufan Ofira , Shahar Danit R. , Sabag Liron , Simon-Tuval Tzahit
Published: January 2022

Eating in catering systems has been identified as a driver of poor diet quality. Interventions within catering systems increase the nutrient density of dishes. Little is known about the incremental costs associated with this strategy. One part of the NEKST (Nutrition Environmental Kibbutzim Study) intervention was nutritional improvement of recipes (decreasing the amount of energy, sodium, and saturated fat). We evaluated the nutritional content of dishes per 100 g and the incremental costs associated with these changes from the catering system’s perspective, as well as diners’ satisfaction with the catering system before and after the intervention. Our results revealed that as energy and saturated fat decreased, the associated incremental cost increased (rs = −0.593, p = 0.010 and rs = −0.748, p < 0.001, respectively). However, the decrease in sodium was not associated with increased costs (rs = 0.099, p = 0.696). While diners’ satisfaction decreased in the control group, it did not change in the intervention group following the intervention (p = 0.018). We concluded that recipe modification improved the nutritional value of dishes without increasing cost. This intervention was not associated with decreased diner satisfaction. This evidence encourages the implementation of policies to improve the nutritional quality of food served by caterers without jeopardizing sales and with the potential to improve public health.
The Ketogenic Diet: Is It an Answer for Sarcopenic Obesity?
Authors: Ilyas Zahra , Perna Simone , A. Alalwan Tariq , Zahid Muhammad Nauman , Spadaccini Daniele , Gasparri Clara , Peroni Gabriella , Faragli Alessandro , Alogna Alessio , La Porta Edoardo , Ali Redha Ali , Negro Massimo , Cerullo Giuseppe , D’Antona Giuseppe , Rondanelli Mariangela
Published: January 2022

This review aims to define the effectiveness of the ketogenic diet (KD) for the management of sarcopenic obesity. As the combination of sarcopenia and obesity appears to have multiple negative metabolic effects, this narrative review discusses the effects of the ketogenic diet as a possible synergic intervention to decrease visceral adipose tissue (VAT) and fatty infiltration of the liver as well as modulate and improve the gut microbiota, inflammation and body composition. The results of this review support the evidence that the KD improves metabolic health and expands adipose tissue γδ T cells that are important for glycaemia control during obesity. The KD is also a therapeutic option for individuals with sarcopenic obesity due to its positive effect on VAT, adipose tissue, cytokines such as blood biochemistry, gut microbiota, and body composition. However, the long-term effect of a KD on these outcomes requires further investigations before general recommendations can be made.
The Antimicrobial Properties of Poplar and Aspen–Poplar Propolises and Their Active Components against Selected Microorganisms, including Helicobacter pylori
Authors: Widelski Jarosław , Okińczyc Piotr , Paluch Emil , Mroczek Tomasz , Szperlik Jakub , Żuk Magdalena , Sroka Zbigniew , Sakipova Zuriyadda , Chinou Ioanna , Skalicka-Woźniak Krystyna , Malm Anna , Korona-Głowniak Izabela
Published: January 2022

There is a noticeable interest in alternative therapies where the outcome is the eradication of the Gram-negative bacterium, Helicobacter pylori (H. pylori), for the purpose of treating many stomach diseases (chronic gastritis and peptic ulcers) and preventing stomach cancer. It is especially urgent because the mentioned pathogen infects over 50% of the world’s population. Recent studies have shown the potential of natural products, such as medicinal plant and bee products, on the inhibition of H. pylori growth. Propolis is such a bee product, with known antimicrobial activities. The main scope of the study is the determination of the antimicrobial activity of ethanolic extracts from 11 propolis samples (mostly from Poland, Ukraine, Kazakhstan, and Greece) against H. pylori, as well as selected bacterial and yeast species. The most effective against H. pylori was the propolis from Ukraine, with an MIC = 0.02 mg/mL while the rest of samples (except one) had an MIC = 0.03 mg/mL. Moreover, significant antimicrobial activity against Gram+ bacteria (with an MIC of 0.02–2.50 mg/mL) and three yeasts (with an MIC of 0.04–0.63 mg/mL) was also observed. A phytochemical analysis (polyphenolic profile) of the propolis samples, by ultra-high-performance liquid chromatography-diode array detector-mass spectrometry (UPLC-DAD-MS), was performed. An evaluation of the impact of the propolis components on antimicrobial activity, consisting of statistical analyses (principal component analysis (PCA) and hierarchical fuzzy clustering), was then performed. It was observed that the chemical composition characteristics of the poplar propolis correlated with higher antibacterial activity, while that of the poplar and aspen propolis correlated with weaker antibacterial activity. To summarize the activity in vitro, all tested propolis samples indicate that they can be regarded as useful and potent factors in antimicrobial therapies, especially against H. pylori.
Wound-Healing Potential of Rhoifolin-Rich Fraction Isolated from Sanguisorba officinalis Roots Supported by Enhancing Re-Epithelization, Angiogenesis, Anti-Inflammatory, and Antimicrobial Effects
Authors: Negm Walaa A. , El-Kadem Aya H. , Elekhnawy Engy , Attallah Nashwah G. M. , Al-Hamoud Gadah Abdulaziz , El-Masry Thanaa A. , Zayed Ahmed
Published: January 2022

A wound is a complicated bioprocess resulting in significant tissue damage, which is worsened by a secondary bacterial infection, commonly Pseudomonas aeruginosa and Staphylococcus aureus. The goal of our study was to investigate the metabolic profile and possible wound-healing effect of Sanguisorba officinalis roots rhoifolin rich fraction (RRF). The LC-ESI-MS/MS analysis of S. officinalis roots crude ethanol extract resulted in a tentative identification of 56 bioactive metabolites, while a major flavonoid fraction was isolated by column chromatography and identified by thin-layer chromatography coupled with electrospray ionization/mass spectrometry (TLC-ESI/MS), where rhoifolin was the major component representing 94.5% of its content. The antibiofilm activity of RRF on the mono-species and dual-species biofilm of P. aeruginosa and S. aureus was investigated. RRF exhibited inhibitory activity on P. aeruginosa and S. aureus mono-species biofilm at 2× minimum inhibitory concentration (MIC) and 4× MIC values. It also significantly inhibited the dual-species biofilm at 4× MIC values. Moreover, the wound-healing characteristics of RRF gel formulation were investigated. Rats were randomly allocated into four groups (eight rats in each): Untreated control; Blank gel; Betadine cream, and RRF gel groups. Animals were anesthetized, and full-thickness excisional skin wounds were created on the shaved area in the dorsal skin. The gels were topically applied to the wound’s surface daily for 10 days. The results demonstrated that RRF had a promising wound-healing effect by up-regulating the platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), and fibronectin, while metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), IL-1β, and nitric oxide (NO) levels were suppressed. It also enhanced the immune staining of transforming growth factor (TGF-β) and improved histopathological findings. Furthermore, it displayed an immunomodulatory action on lipopolysaccharide-induced peripheral blood mononuclear cells. Hence, the wound-healing effect of rhoifolin was confirmed by supporting re-epithelization, angiogenesis, antibacterial, immunomodulatory, and anti-inflammatory activities.
Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α
Authors: Annunziata Chiara , Pirozzi Claudio , Lama Adriano , Senzacqua Martina , Comella Federica , Bordin Antonella , Monnolo Anna , Pelagalli Alessandra , Ferrante Maria Carmela , Mollica Maria Pina , Iossa Angelo , De Falco Elena , Mattace Raso Giuseppina , Cinti Saverio , Giordano Antonio , Meli Rosaria
Published: January 2022

The potential role of brown and beige adipose tissue against obesity has been recognized. Browning, or beiging of white adipose tissue (WAT) is associated with the remodeling of adipocytes and the improvement of their metabolic and secretory functions. Here, palmitoylethanolamide (PEA) restore the plasticity of brown and white adipocytes impaired in mice on a high-fat diet (HFD). Young male C57Bl/6J mice were fed with control (STD) diet or HFD for 12 weeks. Ultramicronized PEA (30 mg/kg/die p.o.) was administered for an additional 7 weeks, together with HFD. PEA recovered interscapular brown fat morphology and function, increasing UCP1 positivity, noradrenergic innervation, and inducing the mRNA transcription of several specialized thermogenic genes. PEA promotes the beige-conversion of the subcutaneous WAT, increasing thermogenic markers and restoring leptin signaling and tissue hormone sensitivity. The pivotal role of lipid-sensing peroxisome proliferator-activated receptor (PPAR)-α in PEA effects was determined in mature 3T3-L1. Moreover, PEA improved mitochondrial bioenergetics in mature adipocytes measured by a Seahorse analyzer and induced metabolic machinery via AMPK phosphorylation. All these outcomes were dampened by the receptor antagonist GW6471. Finally, PEA induced adipogenic differentiation and increased AMPK phosphorylation in human adipose-derived stromal cells (ASCs) obtained from subcutaneous WAT of normal-weight patients and patients with obesity. We identify PEA and PPAR-α activation as the main mechanism by which PEA can rewire energy-storing white into energy-consuming brown-like adipocytes via multiple and converging effects that restore WAT homeostasis and metabolic flexibility.
With a Little Help from My Cell Wall: Structural Modifications in Pectin May Play a Role to Overcome Both Dehydration Stress and Fungal Pathogens
Authors: Forand Ariana D. , Finfrock Y. Zou , Lavier Miranda , Stobbs Jarvis , Qin Li , Wang Sheng , Karunakaran Chithra , Wei Yangdou , Ghosh Supratim , Tanino Karen K.
Published: January 2022

Cell wall structural modifications through pectin cross-linkages between calcium ions and/or boric acid may be key to mitigating dehydration stress and fungal pathogens. Water loss was profiled in a pure pectin system and in vivo. While calcium and boron reduced water loss in pure pectin standards, the impact on Allium species was insignificant (p > 0.05). Nevertheless, synchrotron X-ray microscopy showed the localization of exogenously applied calcium to the apoplast in the epidermal cells of Allium fistulosum. Exogenous calcium application increased viscosity and resistance to shear force in Allium fistulosum, suggesting the formation of calcium cross-linkages (“egg-box” structures). Moreover, Allium fistulosum (freezing tolerant) was also more tolerant to dehydration stress compared to Allium cepa (freezing sensitive). Furthermore, the addition of boric acid (H3BO3) to pure pectin reduced water loss and increased viscosity, which indicates the formation of RG-II dimers. The Arabidopsis boron transport mutant, bor1, expressed greater water loss and, based on the lesion area of leaf tissue, a greater susceptibility to Colletotrichum higginsianum and Botrytis cinerea. While pectin modifications in the cell wall are likely not the sole solution to dehydration and biotic stress resistance, they appear to play an important role against multiple stresses.
A New Green Composite Based on Plasticized Polylactic Acid Mixed with Date Palm Waste for Single-Use Plastics Applications
Authors: Mousa Noran , Galiwango Emmanuel , Haris Sabeera , Al-Marzouqi Ali H. , Abu-Jdayil Basim , Caires Yousuf L.
Published: January 2022

Petroleum-based plastic is widely used in almost all fields. However, it causes serious threats to the environment owing to its non-biodegradable properties, which necessitates finding biodegradable alternatives. Here, date palm rachis (DPR) waste was used as a filler (30, 40, and 50 wt%) to form a biodegradable composite with polylactic acid (PLA) and achieve cost–performance balance. DPR–PLA composites were prepared using a melt-mixing extruder at 180 °C by varying mixing time, DPR composition, and plasticizer type and composition. The biodegradable testing specimens were prepared by compression molding and analyzed using physical, thermal, and mechanical characterizations. Scanning electron microscopy images indicated a uniform dispersion of DPR (90 μm) in the PLA matrix. The esterification reaction resulting from this interaction between DPR and PLA was confirmed by Fourier transform infrared spectroscopy. The 30 wt% DPR–PLA composite was considered the optimal composite with the lowest melt flow index (16 g/10 min). This work confirmed the superior effect of addition of 10 wt% of triethyl citrate (TEC) compared with polybutylene adipate terephthalate (PBAT) by the improvement in the elongation at break of the optimal composite from 2.10% to 4.20%. Moreover, the addition of 10 wt% of PBAT to the optimal composite resulted in a lower tensile strength (21.80 MPa) than that of the composite with 10 wt% of TEC (33.20 MPa). These results show the potential of using the proposed composite as an alternative material for single-use plastics such as cutlery.
Evaluation of the Removal of Organic Matter and Nutrients in the Co-Treatment of Fruit and Vegetable Waste Using a Bioreactor-Constructed Wetlands System
Authors: Orduña-Gaytán Francisco , Vallejo-Cantú Norma A. , Alvarado-Vallejo Andrea , Rosas-Mendoza Erik Samuel , Sandoval-Herazo Luis Carlos , Alvarado-Lassman Alejandro
Published: January 2022

This article presents the application of a novel system for the treatment of fruit and vegetable waste (FVW) using the combination of treatment by the application of the liquid fraction to an anaerobic hydrolytic bioreactor and a constructed wetland. The batch-fed anaerobic bioreactor (AB) had an average organic loading rate of 44 g COD/L-d and a hydraulic residence time (HRT) of 24 h for the degradation of the liquid fraction of the FVW with an average COD removal of 55%. Subsequently, the constructed wetlands (CWs) were fed a subsurface vertical flow of the effluent from the AB by stepwise concentration increments from 1 to 12 g COD/L and a HRT = 72 h until the limit conditions of the operation were identified. For the tropical ornamental species of the CWs in red volcanic gravel (RVG) and RVG + polyethylene (PE) supports, the monoculture of Hippeastrum rutilum and Spathiphyllum wallisii presented removals of COD, Tot-P, and TKN of 90%, 80%, and 85%, respectively. The polycultures with both species exceeded 90% effectiveness. At the end of both processes, a concentration of ~0.5 g COD/L was achieved, confirming that the use of these technologies together constitutes an efficient system for the treatment of the liquid fraction of FVW.