bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Compartment Syndrome after Protobothrops mucrosquamatus Snakebite by Diastolic Retrograde Arterial Flow: A Case Report
Authors: Hou Yueh-Tseng , Chang Meing-Chung , Yang Ching , Chen Yu-Long , Lin Po-Chen , Yiang Giou-Teng , Wu Meng-Yu
Published: July 2022

Post-snakebite compartment syndrome (PSCS) is an uncommon but dangerous condition. Compartment syndrome-like symptoms after snakebite by Protobothrops mucrosquamatus (P. mucrosquamatus) are not effective in guiding fasciotomy. Objective evaluation of intracompartmental pressure measurements in patients with suspected PSCS is recommended. However, there is a lack of consensus regarding PSCS and indications for surgical intervention, including the threshold value of chamber pressure. In addition, intracompartmental pressure measurements may not be readily available in all emergency service settings. Measuring intracompartmental pressure in all snakebite patients for early diagnosis of PSCS is impractical. Therefore, identifying risk factors, continuous real-time monitoring tools, and predictive factors for PSCS are important. Sonography has proved useful in identifying the location and extension of edema after a snakebite. In this study, we attempted to use point-of-care ultrasound to manage PSCS in real-time. Here, we describe a rare case of snakebite from P. mucrosquamatus. PSCS was considered as diastolic retrograde arterial flow (DRAF) was noted in the affected limb with a cobblestone-like appearance in the subcutaneous area, indicating that the target artery was compressed. The DRAF sign requires physicians to aggressively administer antivenom to salvage the limb. The patient was administered 31 vials of P. mucrosquamatus antivenom, and fasciotomy was not performed. DRAF is an early sign of the prediction of PSCS.
Artificial Intelligence Accurately Detects Traumatic Thoracolumbar Fractures on Sagittal Radiographs
Authors: Rosenberg Guillermo Sánchez , Cina Andrea , Schiró Giuseppe Rosario , Giorgi Pietro Domenico , Gueorguiev Boyko , Alini Mauro , Varga Peter , Galbusera Fabio , Gallazzi Enrico
Published: July 2022

Background and Objectives: Commonly being the first step in trauma routine imaging, up to 67% fractures are missed on plain radiographs of the thoracolumbar (TL) spine. The aim of this study was to develop a deep learning model that detects traumatic fractures on sagittal radiographs of the TL spine. Identifying vertebral fractures in simple radiographic projections would have a significant clinical and financial impact, especially for low- and middle-income countries where computed tomography (CT) and magnetic resonance imaging (MRI) are not readily available and could help select patients that need second level imaging, thus improving the cost-effectiveness. Materials and Methods: Imaging studies (radiographs, CT, and/or MRI) of 151 patients were used. An expert group of three spinal surgeons reviewed all available images to confirm presence and type of fractures. In total, 630 single vertebra images were extracted from the sagittal radiographs of the 151 patients—302 exhibiting a vertebral body fracture, and 328 exhibiting no fracture. Following augmentation, these single vertebra images were used to train, validate, and comparatively test two deep learning convolutional neural network models, namely ResNet18 and VGG16. A heatmap analysis was then conducted to better understand the predictions of each model. Results: ResNet18 demonstrated a better performance, achieving higher sensitivity (91%), specificity (89%), and accuracy (88%) compared to VGG16 (90%, 83%, 86%). In 81% of the cases, the “warm zone” in the heatmaps correlated with the findings, suggestive of fracture within the vertebral body seen in the imaging studies. Vertebras T12 to L2 were the most frequently involved, accounting for 48% of the fractures. A4, A3, and A1 were the most frequent fracture types according to the AO Spine Classification. Conclusions: ResNet18 could accurately identify the traumatic vertebral fractures on the TL sagittal radiographs. In most cases, the model based its prediction on the same areas that human expert classifiers used to determine the presence of a fracture.
Hydrophilization of Hydrophobic Mesoporous High-Density Polyethylene Membranes via Ozonation
Authors: Tyubaeva Polina M. , Tyubaev Mikhail A. , Podmasterev Vyacheslav V. , Bolshakova Anastasia V. , Arzhakova Olga V.
Published: July 2022

This work addresses hydrophilization of hydrophobic mesoporous membranes based on high-density polyethylene (HDPE) via ozonation. Mesoporous HDPE membranes were prepared by intercrystallite environmental crazing. Porosity was 50%, and pore dimensions were below 10 nm. Contact angle of mesoporous membranes increases from 96° (pristine HDPE) to 120° due to the formation of nano/microscale surface relief and enhanced surface roughness. The membranes are impermeable to water (water entry threshold is 250 bar). The prepared membranes were exposed to ozonation and showed a high ozone uptake. After ozonation, the membranes were studied by different physicochemical methods, including DSC, AFM, FTIR spectroscopy, etc. Due to ozonation, wettability of the membranes was improved: their contact angle decreased from 120° down to 60°, and they became permeable to water. AFM micrographs revealed a marked smoothening of the surface relief, and the FTIR spectra indicated the development of new functionalities due to ozonolysis. Both factors contribute to hydrophilization and water permeability of the ozonated HDPE membranes. Hence, ozonation was proved to be a facile and efficient instrument for surface modification of hydrophobic mesoporous HDPE membranes and can also provide their efficient sterilization for biomedical purposes and water treatment.
Effect of B2O3 Addition and CaO/Al2O3 Ratios on Melt Structure and Viscosity of CaO–Al2O3-Based Slags
Authors: Zhang Xiaobo , Liu Chengjun , Jiang Maofa
Published: July 2022

The effect of the addition of B2O3 and the CaO/Al2O3 ratios on the CaO–Al2O3–B2O3 melts’ structure was fully analyzed by molecular dynamics (MD) simulations. The results show that, with the increase in CaO/Al2O3 ratios, the charge compensation for [AlO4]5− tetrahedron changed from the oxygen tricluster structure to the charge provided by Ca2+, and the structure of [AlO4]5− tetrahedron was stabilized. The addition of B2O3 reduced the degree of polymerization of the aluminate melt, which, in turn, lowered the melt viscosity; in the systems with CaO/Al2O3 mole ratio less than 1, the added B2O3 mainly existed in the form of [BO3]3−, which reduced the symmetry and the strength of the melt network structures; in the higher CaO/Al2O3 ratio systems, the depolymerization ability of the addition of B2O3 on aluminate network structures was enhanced with the increase in CaO/Al2O3 ratios, and the overall degree of polymerization of the melt decreased. The viscosity measurement shows that B2O3 lowers the viscosity of CaO–Al2O3 melts, which was consistent with the results predicted by MD simulations.
Effect of Hot Dip Plating Process Parameters on Microstructure and Properties of Zinc–10%Aluminum–Mischmetal Alloy Coated for Bridge Cable Steel Wire
Authors: Zhu Xiaoxiong , Shen Yifu , Ge Yunpeng , Zhang Sheng
Published: July 2022

In this work, the effect of the hot dip plating process on the microstructure and properties of zinc–10%aluminum–mischmetal (Zn-10Al-MM) alloy coated for bridge cable wire was studied by changing the hot dip plating temperature, time, and cooling mode. An optical microscope was used to observe the microstructure of the coating and steel wire at low power; a GeminiSEM300 field emission scanning electron microscope was used to observe the microstructure of the coating and steel wire at high power. The hot dip planting temperature is 450 °C, the hot dip plating time is 30 s and 45 s, whether water cooling or air cooling, the hot dip coating structure is relatively uniform, and the grain size is small, the hot dip coating thickness is thick. The coating with 450 °C, 45 s, and the water-cooling process has the highest tensile strength. The corrosion resistance of the hot dip coatings under different processes is higher in the salt spray test. Based on the results of the electrochemical test and salt spray test, the best corrosion resistance of the coatings under 450 °C, 45 s, and the water-cooling process is obtained.
Differential Chemical Profile of Metabolite Extracts Produced by the Diaporthe citri (G-01) Endophyte Mediated by Varying the Fermented Broth pH
Authors: Polonio Julio , Ribeiro Marcos , Fávaro-Polonio Cintia , Meurer Eduardo , Azevedo João , Golias Halison , Pamphile João
Published: July 2022

Endophytic microorganisms show great potential for biotechnological exploitation because they are able to produce a wide range of secondary compounds involved in endophyte–plant adaptation, and their interactions with other living organisms that share the same microhabitat. Techniques used to chemically extract these compounds often neglect the intrinsic chemical characteristics of the molecules involved, such as the ability to form conjugate acids or bases and how they influence the solubilities of these molecules in organic solvents. Therefore, in this study, we aimed to evaluate how the pH of the fermented broth affects the process used to extract the secondary metabolites of the Diaporthe citri strain G-01 endophyte with ethyl acetate as the organic solvent. The analyzed samples, conducted by direct-infusion electrospray-ionization mass spectrometry, were grouped according to the pH of the fermented broth (i.e., <7 and ≥7). A more extreme pH (i.e., 2 or 12) was found to affect the chemical profile of the sample. Moreover, statistical analysis enabled us to determine the presence or absence of ions of high importance; for example, ions at 390.7 and 456.5 m/z were observed mainly at acidic pH, while 226.5, 298.3, and 430.1 m/z ions were observed at pH ≥ 7. Extraction at a pH between 4 and 9 may be of interest for exploring the differential secondary metabolites produced by endophytes. Furthermore, pH influences the chemical phenotype of the fungal metabolic extract.
Improvement of Glycemic Control by a Functional Food Mixture Containing Maltodextrin, White Kidney Bean Extract, Mulberry Leaf Extract, and Niacin-Bound Chromium Complex in Obese Diabetic db/db Mice
Authors: Tzeng Huei-Ping , Chiu Chen-Yuan , Liu Shing-Hwa , Chiang Meng-Tsan
Published: July 2022

Steady-fiber granule (SFG) is a mixture containing maltodextrin, white kidney bean extract, mulberry leaf extract, and niacin-bound chromium complex. These active ingredients have been shown to be associated with improving either hyperglycemia or hyperlipidemia. This study was undertaken to evaluate the potential of SFG in the regulation of blood glucose homeostasis under obese diabetic conditions. Accordingly, db/db mice (8 weeks old) were administered with SFG at doses of 1.025, 2.05, or 5.125 g/kg BW daily via oral gavage for 4 weeks. No body weight loss was observed after SFG supplementation at all three doses during the experimental period. Supplementation of SFG at 2.05 g/kg BW decreased fasting blood glucose, blood fructosamine, and HbA1c levels in db/db mice. Insulin sensitivity was also improved, as indicated by HOMA-IR assessment and oral glucose tolerance test, although the fasting insulin levels were no different in db/db mice with or without SFG supplementation. Meanwhile, the plasma levels of triglyceride were reduced by SFG at all three doses. These findings suggest that SFG improves glycemic control and insulin sensitivity in db/db mice and can be available as an option for functional foods to aid in management of type 2 diabetes mellitus in daily life.
Design, Fabrication, Structure Optimization and Pressure Sensing Demonstration of COC Piezoelectret Sensor and Sensor Array
Authors: Wang Hui , Wang Xiaolin , Wadsworth Matthew , Ahmed Mohammad Faisal , Liu Zhe , Zeng Changchun
Published: July 2022

This study reported on the design and fabrication of a pseudo-piezoelectric material (piezoelectret) from cyclic olefin copolymer (COC) based on a micropillar structure. The fabrication feasibility of such structure was explored and piezoelectret with the good piezoelectric activity (characterized by quasi-static piezoelectric coefficient d33) was demonstrated. Response surface method with a central composite design was employed to investigate the effects of the structure parameter on the piezoelectric coefficient d33. An optimal structure design was obtained and was validated by experiments. With the optimal design, d33 can reach an exceptional high value of ~9000 pC/N under low pressure. The charging process and the electrical and electromechanical characteristics were further investigated by experimentation and modeling. We further demonstrated the scalability of the fabrication process and demonstrated the application of these sensors in position specific pressure sensing (pressure mapping).
Linear and Nonlinear Optical Properties of a Doubly Clamped Suspended Monolayer Graphene Nanoribbon Nanoresonator
Authors: Kosionis Spyridon G. , Paspalakis Emmanuel
Published: July 2022

We studied the optical properties of a hybrid structure that was composed of a semiconductor quantum dot and a doubly clamped suspended graphene nanoribbon nanoresonator. We obtained analytical results for the linear and third-order optical susceptibilities of the hybrid system. The spectrum of the linear susceptibility exhibited a single resonance, and its position depended on the value of the on-resonance exciton energy and the exciton–nanoribbon resonator coupling strength coefficient; the amplitude of the resonance was independent of the values of these parameters. The third-order optical susceptibility spectrum exhibited a sharp resonance arising at low frequencies of the probe field, the position of which depended only on the frequency of the fundamental flexural phonon mode. It also presented a broader resonance arising at higher frequencies of the probe field, the position of which was determined both by the coupling strength coefficient and by the exciton frequency; its amplitude depended solely on the exciton–photon coupling strength.
Fabrication of Microfluidic Tesla Valve Employing Femtosecond Bursts
Authors: Andriukaitis Deividas , Vargalis Rokas , Šerpytis Lukas , Drevinskas Tomas , Kornyšova Olga , Stankevičius Mantas , Bimbiraitė-Survilienė Kristina , Kaškonienė Vilma , Maruškas Audrius Sigitas , Jonušauskas Linas
Published: July 2022

Expansion of the microfluidics field dictates the necessity to constantly improve technologies used to produce such systems. One of the approaches which are used more and more is femtosecond (fs) direct laser writing (DLW). The subtractive model of DLW allows for directly producing microfluidic channels via ablation in an extremely simple and cost-effective manner. However, channel surface roughens are always a concern when direct fs ablation is used, as it normally yields an RMS value in the range of a few µm. One solution to improve it is the usage of fs bursts. Thus, in this work, we show how fs burst mode ablation can be optimized to achieve sub-µm surface roughness in glass channel fabrication. It is done without compromising on manufacturing throughput. Furthermore, we show that a simple and cost-effective channel sealing methodology of thermal bonding can be employed. Together, it allows for production functional Tesla valves, which are tested. Demonstrated capabilities are discussed.
Correction: Otic, C.J.C.; Yonemura, S. Effect of Different Surface Microstructures in the Thermally Induced Self-Propulsion Phenomenon. Micromachines 2022, 13, 871
Authors: Otic Clint John Cortes , Yonemura Shigeru
Published: July 2022

The authors wish to make the following corrections to the published paper [...]
Machine Learning Methods for Quantifying Uncertainty in Prospectivity Mapping of Magmatic-Hydrothermal Gold Deposits: A Case Study from Juruena Mineral Province, Northern Mato Grosso, Brazil
Authors: Silva dos Santos Victor , Gloaguen Erwan , Hector Abud Louro Vinicius , Blouin Martin
Published: July 2022

Mineral prospectivity mapping (MPM), like other geoscience fields, is subject to a variety of uncertainties. When data about unfavorable sites to find deposits (i.e., drill intersections to barren rocks) is lacking in MPM using machine learning (ML) methods, the synthetic generation of negative datasets is required. As a result, techniques for selecting point locations to represent negative examples must be employed. Several approaches have been proposed in the past; however, one can never be certain that the points chosen are true negatives or, at the very least, optimal for training. As a consequence, methodologies that account for the uncertainty of the generation of negative datasets in MPM are needed. In this paper, we compare two criteria for selecting negative examples and quantify the uncertainty associated with this process by generating 400 potential maps for each of the three ML methods utilized (200 maps for each criterion), which include random forest (RF), support vector machine (SVM), and k-nearest neighbors (KNC). The results showed that applying a geological constraint to the creation of negative datasets reduced prediction uncertainty and improved overall model performance but produced larger areas of very high probability (i.e., >0.9) when compared to using only the spatial distribution of known deposits and occurrences as a constraint. SHAP values were used to find approximations for the importance of features in nonlinear methods, and kernel density estimations were used to examine how they varied depending on the negative dataset used to train the ML models. Prospectivity models for magmatic-hydrothermal gold deposits were generated using data from the shuttle radar terrain mission, gamma-ray, magnetic lineaments, and proximity to dykes. The Juruena Mineral Province, situated in Northern Mato Grosso, Brazil, represented the case study for this work.
Tectono-Thermal Events of Coal-Bearing Basin in the Northern North China Craton: Evidence from Zircon–Apatite Fission Tracks and Vitrinite Reflectance
Authors: Liu Dongna , Lin Junwei , Zhou Anchao , Zhao Fenghua , Zhou Rui , Zou Yu
Published: July 2022

In order to further reveal the tectonic activity of the central and northern North China Craton (NCC) since late Paleozoic, the Datong coal-bearing basin was selected as the research object. The tectono-thermal events and uplifting cooling events of the basin were retrieved through zircon and apatite fission tracks and vitrinite reflectance measurements. The research shows that the Datong coal-bearing basin experienced three tectono-thermal events with ages of 245–207 Ma (middle–late Triassic), 179 ± 9 Ma (early Jurassic), and 140 Ma to 78 ± 11 Ma (middle–late Cretaceous), respectively. That just coincides with the lamprophyre activity, Kouquan fault activity, and Zuoyun basaltic andesite magmatic activity which surround the Datong coalfield. The basin also experienced three uplift events with the peak ages of 202 ± 18 Ma (late Triassic), 157 ± 7 Ma (late Jurassic), and 45 ± 3 Ma or 36 ± 3 Ma (middle Eocene), respectively. The Datong Permo-Carboniferous and Jurassic coal vitrinite reflectance proved that the average metamorphism temperature is 104–108 °C, even reaching 163–367 °C. The fission track results showed that the paleotemperature was even higher than 170–250 °C from 117 to 282 Ma and 80–120 °C from 20 to 68 Ma, in the Datong coal-bearing basin. The results show that the deep tectonic activities of the NCC were still active in the Mesozoic and even Cenozoic Paleogene.
Action of Mangifera indica Leaf Extract on Acne-Prone Skin through Sebum Harmonization and Targeting C. acnes
Authors: Tollenaere Morgane De , Boira Cloé , Chapuis Emilie , Lapierre Laura , Jarrin Cyrille , Robe Patrick , Zanchetta Catherine , Vilanova David , Sennelier-Portet Bénédicte , Martinez Jessy , Scandolera Amandine , Auriol Daniel , Reynaud Romain
Published: July 2022

(1) Background: Preclinical studies report that the ethanolic fraction from Mangifera indica leaves is a potential anti-acne agent. Nevertheless, the biological activity of Mangifera indica leaves has scarcely been investigated, and additional data are needed, especially in a clinical setting, for establishing the actual effectiveness of Mangifera indica extract as an active component of anti-acne therapy. (2) Methods: The evaluation of the biological activity of Mangifera indica extract was carried out through different experimental phases, which comprised in silico, in vitro, ex vivo and clinical evaluations. (3) Results: In silico and in vitro studies allowed us to identify the phytomarkers carrying the activity of seboregulation and acne management. Results showed that Mangifera indica extract reduced lipid production by 40% in sebocytes, and an improvement of the sebum quality was reported after the treatment in analyses performed on sebaceous glands from skin explants. The evaluation of the sebum quantity and quality using triglyceride/free fatty acid analysis conducted on Caucasian volunteers evidenced a strong improvement and a reduction of porphyrins expression. The C. acnes lipase activity from a severe acne phylotype was evaluated in the presence of Mangifera indica, and a reduction by 29% was reported. In addition, the analysis of the skin microbiota documented that Mangifera indica protected the microbiota equilibrium while the placebo induced dysbiosis. (4) Conclusions: Our results showed that Mangifera indica is microbiota friendly and efficient against lipase activity of C. acnes and supports a role for Mangifera indica in the therapeutic strategy for prevention and treatment of acne.
Study of Novel Peptides for Antimicrobial Protection in Solution and on Cotton Fabric
Authors: Todorov Petar , Georgieva Stela , Staneva Desislava , Peneva Petia , Grozdanov Petar , Nikolova Ivanka , Vasileva-Tonkova Evgenia , Grabchev Ivo
Published: July 2022

Some new N- and C-modified biomolecular peptide analogues of both VV-hemorphin-5 and VV-hemorphin-7 with varied amino acids (Cys, Glu, His), 1-adamantanecarboxylic acid, and niacin (nicotinic acid) were synthesized by solid-phase peptide synthesis—Fmoc (9-fluorenylmethoxy-carbonyl) chemistry and were characterized in water solutions with different pH using spectroscopic and electrochemical techniques. Basic physicochemical properties related to the elucidation of the peptide structure at physiological pH have been also studied. The results showed that the interaction of peptide compounds with light and electricity preserves the structural and conformational integrity of the compounds in the solutions. Moreover, textile cotton fibers were modified with the new compounds and the binding of the peptides to the surface of the material was proved by FTIR and SEM analysis. Washing the material with an alkaline soap solution did not show a violation of the modified structure of the cotton. Antiviral activity against the human respiratory syncytial virus (HRSV-S2) and human adenovirus serotype 5 (HAdV-5), the antimicrobial activity against B. cereus and P. aeruginosa used as model bacterial strains and cytotoxic effect of the peptide derivatives and modified cotton textile material has been evaluated. Antimicrobial tests showed promising activity of the newly synthesized compounds against the used Gram-positive and Gram-negative bacteria. The compounds C-V, H-V, AC-V, and AH-V were found slightly more active than NH7C and NCH7. The activity has been retained after the deposition of the compounds on cotton fibers.
Development of a Gas-Tight Syringe Headspace GC-FID Method for the Detection of Ethanol, and a Description of the Legal and Practical Framework for Its Analysis, in Samples of English and Welsh Motorists’ Blood and Urine
Authors: Taylor Luke , Saskőy Lili , Brodie Tara , Remeškevičius Vytautas , Moir Hannah Jayne , Barker James , Fletcher John , Kaur Thatti Baljit , Trotter Gavin , Rooney Brian
Published: July 2022

Ethanol is the most commonly used recreational drug worldwide. This study describes the development and validation of a headspace gas chromatography flame ionisation detection (HS-GC-FID) method using dual columns and detectors for simultaneous separation and quantitation. The use of a dual-column, dual-detector HS-GC-FID to quantitate ethanol is a common analytical technique in forensic toxicology; however, most analytical systems utilise pressure-balance injection rather than a simplified gas-tight syringe, as per this technique. This study is the first to develop and validate a technique that meets the specifications of the United Kingdom’s requirements for road traffic toxicology testing using a Shimadzu GC-2014 gas-tight syringe. The calibration ranged from 10 to 400 mg/100 mL, with a target minimum linearity of r2 > 0.999, using tertiary butanol as the internal standard marker. The method has an expanded uncertainty at 99.73% confidence of 3.64% at 80 mg/100 mL, which is the blood alcohol limit for drink driving in England and Wales. In addition, at 200 mg%—the limit at which a custodial sentence may be imposed on the defendant—the expanded uncertainty was 1.95%. For both the 80 mg% and 200 mg% concentrations, no bias was present in the analytical method. This method displays sufficient separation for other alcohols, such as methanol, isopropanol, acetaldehyde, and acetone. The validation of this technique complies with the recommended laboratory guidelines set out by United Kingdom and Ireland Association of Forensic Toxicologists (UKIAFT), the recently issued Laboratory 51 guidelines by the United Kingdom Accreditation Service (UKAS), and the criteria set out by the California Code of Regulations (CCR), 17 CCR § 1220.1.
Zero-Biased Photoelectrochemical Detection of Cardiac Biomarker Myoglobin Based on CdSeS/ZnS Quantum Dots and Barium Titanate Perovskite
Authors: Lima Fernanda M. R. , de Menezes Alan S. , Maciel Adeilton P. , Sinfrônio Francisco S. M. , Kubota Lauro T. , Damos Flávio S. , Luz Rita C. S.
Published: July 2022

Cardiovascular diseases are considered one of the leading causes of premature mortality of patients worldwide. Therefore, rapid diagnosis of these diseases is crucial to ensure the patient’s survival. During a heart attack or severe muscle damage, myoglobin is rapidly released in the body to constitute itself as a precise biomarker of acute myocardial infarction. Thus, we described the photoelectrochemical immunosensor development to detect myoglobin. It was based on fluorine-doped tin oxide modified with CdSeS/ZnSe quantum dots and barium titanate (BTO), designated as CdSeS/ZnSQDS/BTO. It was characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDX), transmission electron microscopy (TEM), X-ray diffraction (XRD), electrochemical impedance spectroscopy (EIS), and amperometry. The anodic photocurrent at the potential of 0 V (vs. Ag/AgCl) and pH 7.4 was found linearly related to the myoglobin (Mb) concentration from 0.01 to 1000 ng mL−1. Furthermore, the immunosensor showed an average recovery rate of 95.7–110.7% for the determination of myoglobin.
Metabolic Engineering of Shikimic Acid Biosynthesis Pathway for the Production of Shikimic Acid and Its Branched Products in Microorganisms: Advances and Prospects
Authors: Wu Sijia , Chen Wenjuan , Lu Sujuan , Zhang Hailing , Yin Lianghong
Published: July 2022

The shikimate pathway is a necessary pathway for the synthesis of aromatic compounds. The intermediate products of the shikimate pathway and its branching pathway have promising properties in many fields, especially in the pharmaceutical industry. Many important compounds, such as shikimic acid, quinic acid, chlorogenic acid, gallic acid, pyrogallol, catechol and so on, can be synthesized by the shikimate pathway. Among them, shikimic acid is the key raw material for the synthesis of GS4104 (Tamiflu®), an inhibitor of neuraminidase against avian influenza virus. Quininic acid is an important intermediate for synthesis of a variety of raw chemical materials and drugs. Gallic acid and catechol receive widespread attention as pharmaceutical intermediates. It is one of the hotspots to accumulate many kinds of target products by rationally modifying the shikimate pathway and its branches in recombinant strains by means of metabolic engineering. This review considers the effects of classical metabolic engineering methods, such as central carbon metabolism (CCM) pathway modification, key enzyme gene modification, blocking the downstream pathway on the shikimate pathway, as well as several expansion pathways and metabolic engineering strategies of the shikimate pathway, and expounds the synthetic biology in recent years in the application of the shikimate pathway and the future development direction.
Identification of Potential Parkinson’s Disease Drugs Based on Multi-Source Data Fusion and Convolutional Neural Network
Authors: Liu Jie , Peng Dongdong , Li Jinlong , Dai Zong , Zou Xiaoyong , Li Zhanchao
Published: July 2022

Parkinson’s disease (PD) is a serious neurodegenerative disease. Most of the current treatment can only alleviate symptoms, but not stop the progress of the disease. Therefore, it is crucial to find medicines to completely cure PD. Finding new indications of existing drugs through drug repositioning can not only reduce risk and cost, but also improve research and development efficiently. A drug repurposing method was proposed to identify potential Parkinson’s disease-related drugs based on multi-source data integration and convolutional neural network. Multi-source data were used to construct similarity networks, and topology information were utilized to characterize drugs and PD-associated proteins. Then, diffusion component analysis method was employed to reduce the feature dimension. Finally, a convolutional neural network model was constructed to identify potential associations between existing drugs and LProts (PD-associated proteins). Based on 10-fold cross-validation, the developed method achieved an accuracy of 91.57%, specificity of 87.24%, sensitivity of 95.27%, Matthews correlation coefficient of 0.8304, area under the receiver operating characteristic curve of 0.9731 and area under the precision–recall curve of 0.9727, respectively. Compared with the state-of-the-art approaches, the current method demonstrates superiority in some aspects, such as sensitivity, accuracy, robustness, etc. In addition, some of the predicted potential PD therapeutics through molecular docking further proved that they can exert their efficacy by acting on the known targets of PD, and may be potential PD therapeutic drugs for further experimental research. It is anticipated that the current method may be considered as a powerful tool for drug repurposing and pathological mechanism studies.
Selective Supercritical CO2 Extraction and Biocatalytic Valorization of Cucurbita pepo L. Industrial Residuals
Authors: Massironi Alessio , Di Fonzo Alessandro , Bassanini Ivan , Ferrandi Erica Elisa , Marzorati Stefania , Monti Daniela , Verotta Luisella
Published: July 2022

The valorization of biomass residuals constitutes a key aspect of circular economy and thus a major challenge for the scientific community. Among industrial wastes, plant residuals could represent an attractive source of bioactive compounds. In this context, a residue from the industrial extraction of Cucurbita pepo L. seeds, whose oil is commercialized for the treatment of genito-urinary tract pathologies, has been selected. Supercritical CO2 technology has been employed as a highly selective “green” methodology allowing the recovery of compounds without chemical degradation and limited operational costs. Free fatty acids have been collected in mild conditions while an enrichment in sterols has been selectively obtained from sc-CO2 extracts by appropriate modulation of process parameters (supercritical fluid pressure and temperature), hence demonstrating the feasibility of the technique to target added-value compounds in a selective way. Obtained fatty acids were thus converted into the corresponding ethanol carboxamide derivatives by lipase-mediated biocatalyzed reactions, while the hydroxylated derivatives of unsaturated fatty acids were obtained by stereoselective hydration reaction under reductive conditions in the presence of a selected FADH2-dependent oleate hydratase.
Multivariate Prognostic Model for Predicting the Outcome of Critically Ill Patients Using the Aromatic Metabolites Detected by Gas Chromatography-Mass Spectrometry
Authors: Pautova Alisa K. , Samokhin Andrey S. , Beloborodova Natalia V. , Revelsky Alexander I.
Published: July 2022

A number of aromatic metabolites of tyrosine and phenylalanine have been investigated as new perspective markers of infectious complications in the critically ill patients of intensive care units (ICUs). The goal of our research was to build a multivariate model for predicting the outcome of critically ill patients regardless of the main pathology on the day of admission to the ICU. Eight aromatic metabolites were detected in serum using gas chromatography-mass spectrometry. The samples were obtained from the critically ill patients (n = 79), including survivors (n = 44) and non-survivors (n = 35), and healthy volunteers (n = 52). The concentrations of aromatic metabolites were statistically different in the critically ill patients and healthy volunteers. A univariate model for predicting the outcome of the critically ill patients was based on 3-(4-hydroxyphenyl)lactic acid (p-HPhLA). Two multivariate classification models were built based on aromatic metabolites using SIMCA method. The predictive models were compared with the clinical APACHE II scale using ROC analysis. For all of the predictive models the areas under the ROC curve were close to one. The aromatic metabolites (one or a number of them) can be used in clinical practice for the prognosis of the outcome of critically ill patients on the day of admission to the ICU.
Effects of the Calix[4]arene Derivative Compound OTX008 on High Glucose-Stimulated ARPE-19 Cells: Focus on Galectin-1/TGF-β/EMT Pathway
Authors: Trotta Maria Consiglia , Petrillo Francesco , Gesualdo Carlo , Rossi Settimio , Corte Alberto Della , Váradi Judit , Fenyvesi Ferenc , D’Amico Michele , Hermenean Anca
Published: July 2022

Diabetic retinopathy (DR) is a neurovascular disease characterized by the reduction of retina integrity and functionality, as a consequence of retinal pigment epithelial cell fibrosis. Although galectin-1 (a glycan-binding protein) has been associated with dysregulated retinal angiogenesis, no evidence has been reported about galectin-1 roles in DR-induced fibrosis. ARPE-19 cells were cultured in normal (5 mM) or high glucose (35 mM) for 3 days, then exposed to the selective galectin-1 inhibitor OTX008 (2.5–5–10 μM) for 6 days. The determination of cell viability and ROS content along with the analysis of specific proteins (by immunocytochemistry, Western blotting, and ELISA) or mRNAs (by real time-PCR) were performed. OTX008 5 μM and 10 μM improved cell viability and markedly reduced galectin-1 protein expression in cells exposed to high glucose. This was paralleled by a down-regulation of the TGF-β/, NF-kB p65 levels, and ROS content. Moreover, epithelial–mesenchymal transition markers were reduced by OTX008 5 μM and 10 μM. The inhibition of galectin-1 by OTX008 in DR may preserve retinal pigment epithelial cell integrity and functionality by reducing their pro-fibrotic phenotype and epithelial–mesenchymal transition phenomenon induced by diabetes.
Bioactive Nitrosylated and Nitrated N-(2-hydroxyphenyl)acetamides and Derived Oligomers: An Alternative Pathway to 2-Amidophenol-Derived Phytotoxic Metabolites
Authors: Girel Sergey , Schütz Vadim , Bigler Laurent , Dörmann Peter , Schulz Margot
Published: July 2022

Incubation of Aminobacter aminovorans, Paenibacillus polymyxa, and Arthrobacter MPI764 with the microbial 2-benzoxazolinone (BOA)-degradation-product 2-acetamido-phenol, produced from 2-aminophenol, led to the recently identified N-(2-hydroxy-5-nitrophenyl) acetamide, to the hitherto unknown N-(2-hydroxy-5-nitrosophenyl)acetamide, and to N-(2-hydroxy-3-nitrophenyl)acetamide. As an alternative to the formation of phenoxazinone derived from aminophenol, dimers- and trimers-transformation products have been found. Identification of the compounds was carried out by LC/HRMS and MS/MS and, for the new structure N-(2-hydroxy-5-nitrosophenyl)acetamide, additionally by 1D- and 2D-NMR. Incubation of microorganisms, such as the soil bacteria Pseudomonas laurentiana, Arthrobacter MPI763, the yeast Papiliotrema baii and Pantoea ananatis, and the plants Brassica oleracea var. gongylodes L. (kohlrabi) and Arabidopsis thaliana Col-0, with N-(2-hydroxy-5-nitrophenyl) acetamide, led to its glucoside derivative as a prominent detoxification product; in the case of Pantoea ananatis, this was together with the corresponding glucoside succinic acid ester. In contrast, Actinomucor elegans consortium synthesized 2-acetamido-4-nitrophenyl sulfate. 1 mM bioactive N-(2-hydroxy-5-nitrophenyl) acetamide elicits alterations in the Arabidopsis thaliana expression profile of several genes. The most responsive upregulated gene was pathogen-inducible terpene synthase TPS04. The bioactivity of the compound is rapidly annihilated by glucosylation.
Conformational Variability of Amyloid-β and the Morphological Diversity of Its Aggregates
Authors: Yagi-Utsumi Maho , Kato Koichi
Published: July 2022

Protein folding is the most fundamental and universal example of biomolecular self-organization and is characterized as an intramolecular process. In contrast, amyloidogenic proteins can interact with one another, leading to protein aggregation. The energy landscape of amyloid fibril formation is characterized by many minima for different competing low-energy structures and, therefore, is much more enigmatic than that of multiple folding pathways. Thus, to understand the entire energy landscape of protein aggregation, it is important to elucidate the full picture of conformational changes and polymorphisms of amyloidogenic proteins. This review provides an overview of the conformational diversity of amyloid-β (Aβ) characterized from experimental and theoretical approaches. Aβ exhibits a high degree of conformational variability upon transiently interacting with various binding molecules in an unstructured conformation in a solution, forming an α-helical intermediate conformation on the membrane and undergoing a structural transition to the β-conformation of amyloid fibrils. This review also outlines the structural polymorphism of Aβ amyloid fibrils depending on environmental factors. A comprehensive understanding of the energy landscape of amyloid formation considering various environmental factors will promote drug discovery and therapeutic strategies by controlling the fibril formation pathway and targeting the consequent morphology of aggregated structures.
Production of O Radicals from Cavitation Bubbles under Ultrasound
Authors: Yasui Kyuichi
Published: July 2022

In the present review, the production of O radicals (oxygen atoms) in acoustic cavitation is focused. According to numerical simulations of chemical reactions inside a bubble using an ODE model which has been validated through studies of single-bubble sonochemistry, not only OH radicals but also appreciable amounts of O radicals are generated inside a heated bubble at the violent collapse by thermal dissociation of water vapor and oxygen molecules. The main oxidant created inside an air bubble is O radicals when the bubble temperature is above about 6500 K for a gaseous bubble. However, the concentration and lifetime of O radicals in the liquid water around the cavitation bubbles are unknown at present. Whether O radicals play some role in sonochemical reactions in the liquid phase, which are usually thought to be dominated by OH radicals and H2O2, should be studied in the future.
Photoelectrochemical Properties of Annealed Anodic TiO2 Layers Covered with CuOx
Authors: Syrek Karolina , Sołtys-Mróz Monika , Pawlik Kinga , Gurgul Magdalena , Sulka Grzegorz D.
Published: July 2022

In this work, we present a systematic study on the influence of Cu2+ ion concentration in the impregnation solution on the morphology, structure, optical, semiconducting, and photoelectrochemical properties of anodic CuOx-TiO2 materials. Studied materials were prepared by immersion in solutions with different concentrations of (CH3COO)2Cu and subjected to air-annealing at 400 °C, 500 °C, or 600 °C for 2 h. The complex characterization of all studied samples was performed using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), reflectance measurements, Mott–Schottky analyses, and photocurrent measurements. It was found that band gap engineering based on coupling CuO with TiO2 (Eg~3.3 eV) is an effective strategy to increase the absorption in visible light due to band gap narrowing (CuOx-TiO2 materials had Eg~2.4 eV). Although the photoactivity of CuO-TiO2 materials decreased in the UV range due to the deposition of CuO on the TiO2 surface, in the Vis range increased up to 600 nm at the same time.
Ethoxy Groups on ZrO2, CuO, and CuO/ZrO2 Studied by IR Spectroscopy
Authors: Podobiński Jerzy , Śliwa Michał , Datka Jerzy
Published: July 2022

The formation, properties, decomposition and reactions of ethoxy groups on ZrO2, CuO, and CuO/ZrO2 were followed by IR spectroscopy. The reaction of ethanol with terminal Zr-OH groups leads to the formation of monodendate ethoxy groups (type I), whereas the reaction of ethanol with tribridged Zr-OH grups results in the formation of bidendate ethoxyls (type II). In both cases, water is produced. Ethoxy groups of type II were also formed on CuO. The type of the surface species detected after interaction of ethanol with CuO/ZrO2 was the same as detected for both oxides (i.e., ZrO2 and CuO) separately. This suggests that no new phase was formed in the mixed oxide system. At higher temperatures, ethoxy groups were oxidized forming acetate ions. Gaseous ethanol present in the cell was oxidized to acetaldehyde without the intermediacy of ethoxy groups.
Advances on Natural Abietane, Labdane and Clerodane Diterpenes as Anti-Cancer Agents: Sources and Mechanisms of Action
Authors: Acquaviva Rosaria , Malfa Giuseppe A. , Loizzo Monica R. , Xiao Jianbo , Bianchi Simone , Tundis Rosa
Published: July 2022

Extensive research over the past decades has identified numerous phytochemicals that could represent an important source of anti-cancer compounds. There is an immediate need for less toxic and more effective preventive and therapeutic strategies for the treatment of cancer. Natural compounds are considered suitable candidates for the development of new anti-cancer drugs due to their pleiotropic actions on target events with multiple manners. This comprehensive review highlighted the most relevant findings achieved in the screening of phytochemicals for anticancer drug development, particularly focused on a promising class of phytochemicals such as diterpenes with abietane, clerodane, and labdane skeleton. The chemical structure of these compounds, their main natural sources, and mechanisms of action were critically discussed.
Exploring the Interaction of G-quadruplex Binders with a (3 + 1) Hybrid G-quadruplex Forming Sequence within the PARP1 Gene Promoter Region
Authors: Mazzini Stefania , Princiotto Salvatore , Artali Roberto , Musso Loana , Aviñó Anna , Eritja Ramon , Gargallo Raimundo , Dallavalle Sabrina
Published: July 2022

The enzyme PARP1 is an attractive target for cancer therapy, as it is involved in DNA repair processes. Several PARP1 inhibitors have been approved for clinical treatments. However, the rapid outbreak of resistance is seriously threatening the efficacy of these compounds, and alternative strategies are required to selectively regulate PARP1 activity. A noncanonical G-quadruplex-forming sequence within the PARP1 promoter was recently identified. In this study, we explore the interaction of known G-quadruplex binders with the G-quadruplex structure found in the PARP gene promoter region. The results obtained by NMR, CD, and fluorescence titration, also confirmed by molecular modeling studies, demonstrate a variety of different binding modes with small stabilization of the G-quadruplex sequence located at the PARP1 promoter. Surprisingly, only pyridostatin produces a strong stabilization of the G-quadruplex-forming sequence. This evidence makes the identification of a proper (3+1) stabilizing ligand a challenging goal for further investigation.
Particles Morphology Impact on Cytotoxicity, Hemolytic Activity and Sorption Properties of Porous Aluminosilicates of Kaolinite Group
Authors: Golubeva Olga Yu. , Alikina Yulia A. , Brazovskaya Elena Yu.
Published: July 2022

A comparative study of the properties of aluminosilicates of the kaolinite (Al2Si2O5(OH)4∙nH2O) group with different particles morphology has been carried out. Under conditions of directed hydrothermal synthesis, kaolinite nanoparticles with spherical, sponge, and platy morphologies were obtained. Raw nanotubular halloysite was used as particles with tubular morphology. The samples were studied by X-ray diffraction, SEM, solid-state NMR, low-temperature nitrogen adsorption, and the dependence of the zeta potential of the samples on the pH of the medium was defined. The sorption capacity with respect to cationic dye methylene blue in aqueous solutions was studied. It was found that sorption capacity depends on particles morphology and decreases in the series spheres-sponges-tubes-plates. The Langmuir, Freundlich, and Temkin models describe experimental methylene blue adsorption isotherms on aluminosilicates of the kaolinite subgroup with different particles morphology. To process the kinetic data, pseudo-first order and pseudo-second order were used. For the first time, studies of the dependence of hemolytic activity and cytotoxicity of aluminosilicate nanoparticles on their morphology were carried out. It was found that aluminosilicate nanosponges and spherical particles are not toxic to human erythrocytes and do not cause their destruction at sample concentrations from 0.1 to 1 mg/g. Based on the results of the MTT test, the concentration value that causes 50% inhibition of cell population growth (IC50, mg/mL) was calculated. For nanotubes, this value turned out to be the smallest—0.33 mg/mL. For samples with platy, spherical and nanosponge morphology, the IC50 values were 1.55, 2.68, and 4.69 mg/mL, respectively.
A Critical Analysis on the Sensitivity Enhancement of Surface Plasmon Resonance Sensors with Graphene
Authors: dos Santos Almeida Aline , Bahamon Dario A. , Peres Nuno M. R. , de Matos Christiano J. S.
Published: July 2022

The use of graphene in surface plasmon resonance sensors, covering a metallic (plasmonic) film, has a number of demonstrated advantages, such as protecting the film against corrosion/oxidation and facilitating the introduction of functional groups for selective sensing. Recently, a number of works have claimed that few-layer graphene can also increase the sensitivity of the sensor. However, graphene was treated as an isotropic thin film, with an out-of-plane refractive index that is identical to the in-plane index. Here, we critically examine the role of single and few layers of graphene in the sensitivity enhancement of surface plasmon resonance sensors. Graphene is introduced over the metallic film via three different descriptions: as an atomic-thick two-dimensional sheet, as a thin effective isotropic material (same conductivity in the three coordinate directions), and as an non-isotropic layer (different conductivity in the perpendicular direction to the two-dimensional plane). We find that only the isotropic layer model, which is known to be incorrect for the optical modeling of graphene, provides sizable sensitivity increases, while the other, more accurate, models lead to a negligible contribution to the sensitivity.