bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Relative Threshold of Abnormal Travel in Subway Based on Bilateral Curve Fitting
Authors: Zou Liang , Cao Ke , Zhu Lingxiang
Published: April 2023

Abnormal passenger behavior in rail transit has become a top priority, as it affects operational safety. Passenger travel time is the main basis for identifying abnormal behavior while considering the flexibility of travel time. Currently, the main method is to use absolute threshold discrimination based on the distribution of travel time. However, there is a problem of missing abnormal passenger behavior due to the large difference in travel time between the Origin-Destinations (ODs). Therefore, this paper proposes a method of setting corresponding thresholds for each OD. By analyzing the percentile curves of the overall and individual OD pairs, it was found that the turning point of the curve had a significant feature, and the difference between the two sides of the curve was obvious. This paper proposes a bilateral fitting method, and the results show that this method can calculate the relative threshold for different OD pairs. The significant advantages of this method are its low cost and wide coverage.
Positive Periodic Solution for Pipe/Tank Flow Configurations with Friction
Authors: Du Haiqing , Wang Xiaojing , Du Bo
Published: April 2023

In this article, we study a periodic boundary value problem related to valveless pumping. The valveless pumping is described by the unidirectional flow of liquid in a system. We establish some conditions for globally asymptotic stability and the existence of a positive periodic solution to the considered equation. Finally, a numerical example shows that the theoretical results in this paper are feasible.
Non-Associative Structures and Their Applications in Differential Equations
Authors: Krasnov Yakov
Published: April 2023

This article establishes a connection between nonlinear DEs and linear PDEs on the one hand, and non-associative algebra structures on the other. Such a connection simplifies the formulation of many results of DEs and the methods of their solution. The main link between these theories is the nonlinear spectral theory developed for algebra and homogeneous differential equations. A nonlinear spectral method is used to prove the existence of an algebraic first integral, interpretations of various phase zones, and the separatrices construction for ODEs. In algebra, the same methods exploit subalgebra construction and explain fusion rules. In conclusion, perturbation methods may also be interpreted for near-Jordan algebra construction.
Stability and Threshold Dynamics in a Seasonal Mathematical Model for Measles Outbreaks with Double-Dose Vaccination
Authors: Ibrahim Mahmoud A. , Dénes Attila
Published: April 2023

Measles is a highly contagious viral disease that can lead to serious complications, including death, particularly in young children. In this study, we developed a mathematical model that incorporates a seasonal transmission parameter to examine the measles transmission dynamics. We define the basic reproduction number (R0) and show its utility as a threshold parameter for global dynamics and the existence of periodic solutions. The model was applied to the measles outbreak that occurred in Pakistan from 2019 to 2021 and provided a good fit to the observed data. Our estimate of the basic reproduction number was found to be greater than one, indicating that the disease will persist in the population. The findings highlight the need to increase vaccination coverage and efficacy to mitigate the impact of the epidemic. The model also shows the long-term behavior of the disease, which becomes endemic and recurs annually. Our simulations demonstrate that a shorter incubation period accelerates the spread of the disease, while a higher vaccination coverage rate reduces its impact. The importance of the second dose of the measles vaccine is emphasized, and a higher vaccine efficacy rate can also help bring R0 below one. Our study provides valuable information for the development and implementation of effective measles control strategies. To prevent future outbreaks, increasing vaccination coverage among the population is the most effective way to reduce the transmission of measles.
Nonlinear Techniques and Ridge Regression as a Combined Approach: Carcinoma Identification Case Study
Authors: Alfonso Perez Gerardo , Castillo Raquel
Published: April 2023

As more genetic information becomes available, such as DNA methylation levels, it becomes increasingly important to have techniques to analyze such data in the context of cancers such as anal and cervical carcinomas. In this paper, we present an algorithm that differentiates between healthy control patients and individuals with anal and cervical carcinoma, using as an input DNA methylation data. The algorithm used a combination of ridge regression and neural networks for the classification task, achieving high accuracy, sensitivity and specificity. The relationship between methylation levels and carcinoma could in principle be rather complex, particularly given that a large number of CpGs could be involved. Therefore, nonlinear techniques (machine learning) were used. Machine learning techniques (nonlinear) can be used to model linear processes, but the opposite (linear techniques simulating nonlinear models) would not likely generate accurate forecasts. The feature selection process is carried out using a combination of prefiltering, ridge regression and nonlinear modeling (artificial neural networks). The model selected 13 CpGs from a total of 450,000 CpGs available per patient with 171 patients in total. The model was also tested for robustness and compared to other more complex models that generated less precise classifications. The model obtained (testing dataset) an accuracy, sensitivity and specificity of 97.69%, 95.02% and 98.26%, respectively. The reduction of the dimensionality of the data, from 450,000 to 13 CpGs per patient, likely also reduced the likelihood of overfitting, which is a very substantial risk in this type of modelling. All 13 CpGs individually generated classification forecasts less accurate than the proposed model.
Theoretical Structure and Applications of a Newly Enhanced Gumbel Type II Model
Authors: Lone Showkat Ahmad , Sindhu Tabassum Naz , Hassan Marwa K. H. , Abushal Tahani A. , Anwar Sadia , Shafiq Anum
Published: April 2023

Statistical models are vital in data analysis, and researchers are always on the search for potential or the latest statistical models to fit data sets in a variety of domains. To create an improved statistical model, we used a T-X transformation and the Gumbel Type-II model in this investigation. The research examined a simulation evaluation to assess the efficacy of the parameters. To show the application of the T-X approach for producing new distributions titled the new and improved Gumbel Type-II (NIGT-II) distribution, two actual data sets were used. The data sets reveal that the NIGT-II distribution sounds nicer than the Gumbel Type-II distribution.
Verification of Current-State Opacity in Discrete Event Systems by Using Basis Coverability Graphs
Authors: Zhu Haoming , El-Sherbeeny Ahmed M. , El-Meligy Mohammed A. , Fathollahi-Fard Amir M. , Li Zhiwu
Published: April 2023

A new approach to the verification of current-state opacity for discrete event systems is proposed in this paper, which is modeled with unbounded Petri nets. The concept of opacity verification is first extended from bounded Petri nets to unbounded Petri nets. In this model, all transitions and partial places are assumed to be unobservable, i.e., only the number of tokens in the observable places can be measured. In this work, a novel basis coverability graph is constructed by using partial markings and quasi-observable transitions. By this graph, this research finds that an unbounded net system is current-state opaque if, for an arbitrary partial marking, there always exists at least one regular marking in the result of current-state estimation with respect to the partial marking not belonging to the given secret. Finally, a sufficient and necessary condition is proposed for the verification of current-state opacity. A manufacturing system example is presented to illustrate that the concept of current-state opacity can be verified for unbounded net systems.
Spatio-Temporal Gradient Enhanced Surrogate Modeling Strategies
Authors: Bouwer Johann M. , Wilke Daniel N. , Kok Schalk
Published: April 2023

This research compares the performance of space-time surrogate models (STSMs) and network surrogate models (NSMs). Specifically, when the system response varies over time (or pseudo-time), the surrogates must predict the system response. A surrogate model is used to approximate the response of computationally expensive spatial and temporal fields resulting from some computational mechanics simulations. Within a design context, a surrogate takes a vector of design variables that describe a current design and returns an approximation of the design’s response through a pseudo-time variable. To compare various radial basis function (RBF) surrogate modeling approaches, the prediction of a load displacement path of a snap-through structure is used as an example numerical problem. This work specifically considers the scenario where analytical sensitivities are available directly from the computational mechanics’ solver and therefore gradient enhanced surrogates are constructed. In addition, the gradients are used to perform a domain transformation preprocessing step to construct surrogate models in a more isotropic domain, which is conducive to RBFs. This work demonstrates that although the gradient-based domain transformation scheme offers a significant improvement to the performance of the space-time surrogate models (STSMs), the network surrogate model (NSM) is far more robust. This research offers explanations for the improved performance of NSMs over STSMs and recommends future research to improve the performance of STSMs.
Elimination of Lumbar Plexus Injury by Changing the Entry Point and Traction Direction of the Psoas Major Muscle in Transpsoas Lateral Lumbar Spine Surgery
Authors: Nojiri Hidetoshi , Okuda Takatoshi , Takano Hiromitsu , Gomi Motoshi , Takahashi Ryosuke , Shimura Arihisa , Tamagawa Shota , Hara Takeshi , Ohara Yukoh , Ishijima Muneaki
Published: April 2023

Background and Objectives: The lateral approach is commonly used for anterior column reconstruction, indirect decompression, and fusion in patients with lumbar degenerative diseases and spinal deformities. However, intraoperative lumbar plexus injury may occur. This is a retrospective comparative study to investigate and compare neurological complications between the conventional lateral approach and a modified lateral approach at L4/5. Materials and Methods: Patients with a lumbar degenerative disease requiring single-level intervertebral fusion at L4/5 were included and categorized into group X and group A. Patients in group X underwent conventional extreme lateral interbody fusion, while those in group A underwent a modified surgical procedure that included splitting of the anterior third of the psoas muscle, which was dilated by the retractor on the anterior third of the intervertebral disc. The incidence of lumbar plexus injury, defined as a decrease of ≥1 grade on manual muscle testing of hip flexors and knee extensors and sensory impairment of the thigh for ≥3 weeks, on the approach side, was investigated. Results: Each group comprised 50 patients. No significant between-group differences in age, sex, body mass index, and approach side were observed. There was a significant between-group difference in intraoperative neuromonitoring stimulation value (13.1 ± 5.4 mA in group X vs. 18.5 ± 2.3 mA in group A, p < 0.001). The incidence of neurological complications was significantly higher in group X than in group A (10.0% vs. 0.0%, respectively, p < 0.05). Conclusions: In our modified procedure, the anterior third of the psoas muscle was entered and split, and the intervertebral disc could be reached without damaging the lumbar plexus. When performing lumbar surgery using the lateral approach, lumbar plexus injury can be avoided by following surgical indication criteria based on the location of the lumbar plexus with respect to the psoas muscle and changing the transpsoas approach to the intervertebral disc.
Taekwondo Athlete’s Bilateral Achilles Tendon Rupture: A Case Report
Authors: Lee Jun Young , Kim Sung Hwan , Cha Joo Young , Lee Young Koo
Published: April 2023

(1) Background: Achilles tendon rupture is a common sports injury that may result in severe disability. The overall incidence of Achilles tendon rupture is increasing as a result of growing sports participation. However, cases of spontaneous bilateral Achilles tendon rupture with no underlying disease or risk factors, such as systemic inflammatory disease, steroid or (fluoro)quinolone antibiotics use, are rare. (2) Objective: Here, we report a case of a Taekwondo athlete’s bilateral Achilles tendon rupture after kicking and landing. By sharing the experience of treatment and the patient’s course, we suggest one of the possible treatment options and the need to establish a treatment method. (3) Procedure: A 23-year-old male Taekwondo athlete visited the hospital, presenting foot plantar flexion failure and severe pain in both tarsal joints, which had occurred upon kicking and landing on both feet earlier that day. During surgery, no degenerative changes or denaturation were observed in the ruptured areas of the Achilles tendons. Bilateral surgery was performed using the modified Bunnel method on the right side and minimum-section suturing on the left side was performed using the Achillon system, followed by lower limb casting. (4) Result: Good outcomes were observed on both sides at 19 months postoperatively. (5) Conclusion: The possibility of bilateral Achilles tendon rupture during exercise in young subjects with no risk factors should be acknowledged, especially in association with landing. In addition, in athletes, even if there is a possibility of complications, surgical treatment should be considered for functional recovery.
Vitamin E Enhances Cell Viability and the Osteogenic Differentiation of Cell Spheroids Made of Gingiva-Derived Stem Cells
Authors: Kim Jin-Hyeong , Kim Minji , Hwa Somyeong , Ko Youngkyung , Park Jun-Beom
Published: April 2023

Background and Objectives: Vitamin E is reported to expedite new bone formation in animal models, and this has led to a decrease in the time needed for treatment. In this study, human gingiva-derived stem cell-derived spheroids were examined to determine the effects of vitamin E on cell survival, osteogenic differentiation, and mineralization. Materials and Methods: Human gingiva-derived stem cells were used to create spheroids, which were then cultivated with vitamin E at doses of 0, 0.1, 1, 10, and 100 ng/mL. The morphological examination and the qualitative and quantitative vitality of the cells were assessed. Alizarin Red S staining and alkaline phosphatase activity assays were performed on days 7 and 14 to evaluate the osteogenic differentiation. The expression levels of RUNX2 and COL1A1 were assessed using a real-time polymerase chain reaction. Results: The addition of vitamin E did not appear to alter the spheroid’s shape at the measured quantities without altering the diameter. During the culture time, the majority of the cells in the spheroids fluoresced green. Regardless of concentration, there were substantial increases in cell viability in the vitamin E-loaded groups on day 7 (p < 0.05). On day 14, the Alizarin Red S staining was statistically higher in the 1 ng/mL group compared to the unloaded control (p < 0.05). The addition of vitamin E to the culture enhanced the mRNA expression levels of RUNX2, OCN, and COL1A1 based on the real-time polymerase chain reaction data. Conclusions: We draw the conclusion that vitamin E may be used to promote the osteogenic differentiation of stem cell spheroids in light of these data.
Use and Abuse of Electrocautery in Adenoidectomy Hemostasis
Authors: Epure Veronica , Hainarosie Razvan , Voiosu Catalina , Gheorghe Dan Cristian
Published: April 2023

Background and objectives: Bipolar electrocautery is commonly used to control bleeding after cold-instrument pediatric adenoidectomy, but the surgeon should be aware of the possible side effects. OBJECTIVE: The aim of our study is to investigate the effects of bipolar electrocautery when used for bleeding control at the end of an adenoidectomy procedure. Materials and Methods: We evaluated the effect of electrocautery on postoperative pain, velopharyngeal insufficiency symptoms, postoperative nasal obstruction, and rhinorrhea in a group of 90 children undergoing adenoidectomy in our ENT department over a period of 3 months. Results: After statistically analyzing the data, we found that the duration of postoperative pain, the duration of rhinorrhea and nasal obstruction, and the duration of painkiller administration, as well as the velopharyngeal insufficiency symptoms, were significantly longer in patients in whom electrocautery was used for hemostasis. A significantly higher incidence of posterior neck pain and halitosis (oral malodor) was noted in the patients in whom electrocautery was used for adenoidectomy hemostasis. Conclusions: Bipolar electrocautery use should be limited during pediatric adenoidectomy hemostasis because of the possible side effects: longer postoperative pain, prolonged nasal obstruction, rhinorrhea and velopharyngeal insufficiency, and halitosis. We noted some side effects that were specific to electrocautery use during adenoidectomy: posterior neck pain and oral malodor. Acknowledging the risk for these symptoms can help to alleviate the anxiety of both the parents and the patients regarding the expected postoperative outcomes.
Metrological Evaluation of the Compatibility of Two Different Digital Density Meter Adjustment Methods
Authors: Santos Eugênio Benevides dos , Oliveira Elcio Cruz de
Published: April 2023

Brazilian regulation requires the test methods for analysing the shrinkage factor, and the solubility ratio in crude oils must be estimated under the measurement conditions for appropriation. Since these physicochemical parameters depend upon the density, a Brazilian oil company proposed an adapted and more user-friendly methodology for adjusting the digital density meter under high pressure and temperature conditions. This study aimed to evaluate the metrological compatibility of this proposal by comparing it with the fit model presented by a manufacturer of a digital densimeter and with the tabulated reference values of fluid density. Since the density data behaviour presented non-normal distributions, the Wilcoxon signed-rank test showed metrological compatibility between the approaches studied in the pressure range from 0 psi to 1200 psi (8.273709 MPa) and the temperature range from 5 °C to 70 °C.
Hardware Trojan Mitigation Technique in Network-on-Chip (NoC)
Authors: Hussain Musharraf , Baloach Naveed Khan , Ali Gauhar , ElAffendi Mohammed , Dhaou Imed Ben , Ullah Syed Sajid , Uddin Mueen
Published: April 2023

Due to globalization in the semiconductor industry, malevolent modifications made in the hardware circuitry, known as hardware Trojans (HTs), have rendered the security of the chip very critical. Over the years, many methods have been proposed to detect and mitigate these HTs in general integrated circuits. However, insufficient effort has been made for hardware Trojans (HTs) in the network-on-chip. In this study, we implement a countermeasure to congeal the network-on-chip hardware design in order to prevent changes from being made to the network-on-chip design. We propose a collaborative method which uses flit integrity and dynamic flit permutation to eliminate the hardware Trojan inserted into the router of the NoC by a disloyal employee or a third-party vendor corporation. The proposed method increases the number of received packets by up to 10% more compared to existing techniques, which contain HTs in the destination address of the flit. Compared to the runtime HT mitigation method, the proposed scheme also decreases the average latency for the hardware Trojan inserted in the flit’s header, tail, and destination field up to 14.7%, 8%, and 3%, respectively.
A Lab-on-a-Tube Biosensor Combining Recombinase-Aided Amplification and CRISPR-Cas12a with Rotated Magnetic Extraction for Salmonella Detection
Authors: Wu Shangyi , Yuan Jing , Xu Ai , Wang Lei , Li Yanbin , Lin Jianhan , Yue Xiqing , Xi Xinge
Published: April 2023

Background: Foodborne pathogenic bacteria threaten worldwide public health, and simple bacterial detection methods are in urgent need. Here, we established a lab-on-a-tube biosensor for simple, rapid, sensitive, and specific detection of foodborne bacteria. Methods: A rotatable Halbach cylinder magnet and an iron wire netting with magnetic silica beads (MSBs) were used for simple and effective extraction and purification of DNA from the target bacteria, and recombinase-aided amplification (RAA) was combined with clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins12a(CRISPR-Cas12a) to amplify DNA and generate fluorescent signal. First, 15 mL of the bacterial sample was centrifuged, and the bacterial pellet was lysed by protease to release target DNA. Then, DNA-MSB complexes were formed as the tube was intermittently rotated and distributed uniformly onto the iron wire netting inside the Halbach cylinder magnet. Finally, the purified DNA was amplified using RAA and quantitatively detected by the CRISPR-Cas12a assay. Results: This biosensor could quantitatively detect Salmonella in spiked milk samples in 75 min, with a lower detection limit of 6 CFU/mL. The fluorescent signal of 102 CFU/mL Salmonella Typhimurium was over 2000 RFU, while 104 CFU/mL Listeria monocytogenes, Bacillus cereus, and E. coli O157:H7 were selected as non-target bacteria and had signals less than 500 RFU (same as the negative control). Conclusions: This lab-on-a-tube biosensor integrates cell lysis, DNA extraction, and RAA amplification in one 15 mL tube to simplify the operation and avoid contamination, making it suitable for low-concentration Salmonella detection.
Electrothermally Driven Reconfiguration of Microrobotic Beam Structures for the ChipSail System
Authors: Xie Kecai , Li Chengyang , Sun Shouyu , Nam Chang-Yong , Shi Yong , Wang Haipeng , Duan Wu , Ren Zhongjing , Yan Peng
Published: April 2023

Solar sailing enables efficient propellant-free attitude adjustment and orbital maneuvers of solar sail spacecraft with high area-to-mass ratios. However, the heavy supporting mass for large solar sails inevitably leads to low area-to-mass ratios. Inspired by chip-scale satellites, a chip-scale solar sail system named ChipSail, consisting of microrobotic solar sails and a chip-scale satellite, was proposed in this work. The structural design and reconfigurable mechanisms of an electrothermally driven microrobotic solar sail made of Al\Ni50Ti50 bilayer beams were introduced, and the theoretical model of its electro-thermo-mechanical behaviors was established. The analytical solutions to the out-of-plane deformation of the solar sail structure appeared to be in good agreement with the finite element analysis (FEA) results. A representative prototype of such solar sail structures was fabricated on silicon wafers using surface and bulk microfabrication, followed by an in-situ experiment of its reconfigurable property under controlled electrothermal actuation. The experimental results demonstrated significant electro-thermo-mechanical deformation of such microrobotic bilayer solar sails, showing great potential in the development of the ChipSail system. Analytical solutions to the electro-thermo-mechanical model, as well as the fabrication process and characterization techniques, provided a rapid performance evaluation and optimization of such microrobotic bilayer solar sails for the ChipSail.
Nitrobenzoates and Nitrothiobenzoates with Activity against M. tuberculosis
Authors: Pais João P. , Antoniuk Olha , Freire Raquel , Pires David , Valente Emília , Anes Elsa , Constantino Luis
Published: April 2023

Esters of weak acids have shown improved antimycobacterial activity over the corresponding free acids and nitro benzoates in particular have previously shown to have a very intriguing activity. To expand the potential of nitro-derivatives of benzoic acid as antimycobacterial drugs and explore the effects of various structural features on the activity of these compounds, we have obtained a library of 64 derivatives containing esters and thioesters of benzoates and studied their activity against M. tuberculosis, the stability of the compounds, their activation by mycobacterial enzymes and the potential cytotoxicity against human monocytic THP-1 cell line. Our results showed that the most active compounds are those with an aromatic nitro substitution, with the 3,5-dinitro esters series being the most active. Also, the greater antitubercular activity for the nitro derivatives was shown to be unrelated to their pKa values or hydrolysis rates. Given the conventional relationship between nitro-containing substances and toxicity, one might anticipate that the great antimicrobial activity of nitro compounds would be associated with high toxicity; yet, we have not found such a relationship. The nitrobenzoate scaffold, particularly the 3,5-dinitrobenzoate scaffold, merits further investigation, because it has the potential to generate future antimycobacterial agents with improved activity.
Brewing a Craft Belgian-Style Pale Ale Using Pichia kudriavzevii 4A as a Starter Culture
Authors: Nieto-Sarabia Vogar Leonel , Melgar-Lalanne Guiomar , Ballinas-Cesatti Christian Bryan , García-García Fernando Abiram , Jose-Salazar Jorge Alberto , Flores-Ortiz César Mateo , Cristiani-Urbina Eliseo , Morales-Barrera Liliana
Published: April 2023

There is an expanding market for beer of different flavors. This study aimed to prepare a craft Belgian-style pale ale with a non-Saccharomyces yeast. Pichia kudriavzevii 4A was used as a sole starter culture, and malted barley as the only substrate. The ingredients and brewing process were carefully monitored to ensure the quality and innocuousness of the beverage. During fermentation, the yeast consumed 89.7% of total sugars and produced 13.8% v/v of ethanol. The product was fermented and then aged for 8 days, adjusted to 5% v/v alcohol, and analyzed. There were no traces of mycotoxins, lead, arsenic, methanol, or microbiological contamination that would compromise consumer health. According to the physicochemical analysis, the final ethanol concentration (5.2% v/v) and other characteristics complied with national and international guidelines. The ethyl acetate and isoamyl alcohol present are known to confer sweet and fruity flavors. The sensory test defined the beverage as refreshing and as having an apple and pear flavor, a banana aroma, and a good level of bitterness. The judges preferred it over a commercial reference sample of Belgian-style pale ale made from S. cerevisiae. Hence, P. kudriavzevii 4A has the potential for use in the beer industry.
Oral Mycobiome and COVID-19
Authors: D’Ambrosio Francesco
Published: April 2023

The most common signs and symptoms of COVID-19 include fever, cough, dyspnea, conjunctivitis, diarrhea, and olfactory and gustatory disturbances [...]
Phylogenetic and Structural Analysis of Porcine Circovirus Type 2 from 2016 to 2021 in Jilin Province, China
Authors: Chen Si , Li Xue , Zhang Liying , Zheng Jiawei , Yang Lin , Niu Guyu , Zhang Huimin , Ren Ying , Qian Jing , Sun Changjiang , Ren Linzhu
Published: April 2023

Porcine circovirus disease (PCVD) caused by porcine circovirus type 2 (PCV2) is widely distributed in pig farms. Up until now, nine genotypes of PCV2, PCV2a to 2i, have been identified in diseased pigs worldwide. This study analyzed 302 samples collected in the Jilin Province of China from 2016 to 2021, followed by genetic analysis of the PCV2 isolates. Meanwhile, the antigen epitopes, amino acid mutations, 3D structure of the PCV2 isolates and commercially available vaccine strains were evaluated and compared. The results showed that the predominant genotypes of PCV2 were PCV2b, followed by PCV2e and PCV2d in Jilin Province during 2016–2021. Although mutations were detected in the isolates, no recombination occurred in the PCV2 isolates, indicating a stable genotype of PCV2 in Jilin Province during these years. Moreover, the B cell epitopes in the Cap and Rep proteins of eighteen PCV2 isolates and T cell epitopes in the Cap of the isolates were changed compared to three currently used vaccine strains. The mutations in the Cap and Rep proteins did not affect their spatial conformation. Therefore, bivalent or multivalent vaccines with different genotypes of PCV2 might improve the protective effect of vaccines.
Novel Microbial Enzymes with Industrial Applications
Authors: González-Siso María-Isabel , Becerra Manuel
Published: April 2023

Eberhardt et al [...]
Novel 2-Amino-1,4-Naphthoquinone Derivatives Induce A549 Cell Death through Autophagy
Authors: Tan Hua-Yuan , Liang Feng-Ming , Zhang Wen-Jing , Zhang Yi , Cui Jun-Hao , Dai Yu-Yu , Qiu Xue-Mei , Wang Wen-Hang , Zhou Yue , Chen Dan-Ping , Li Cheng-Peng
Published: April 2023

A series of 1,4-naphthoquinone derivatives containing were synthesized as anti-cancer agents and the crystal structure of compound 5a was confirmed by X-ray diffraction. In addition, the inhibitory activities against four cancer cell lines (HepG2, A549, K562, and PC-3) were tested, respectively, and compound 5i showed significant cytotoxicity on the A549 cell line with the IC50 of 6.15 μM. Surprisingly, in the following preliminary biological experiments, we found that compound 5i induced autophagy by promoting the recycling of EGFR and signal transduction in the A549 cell, resulting in the activation of the EGFR signal pathway. The potential binding pattern between compound 5i and EGFR tyrosine kinase (PDB ID: 1M17) was also identified by molecular docking. Our research paves the way for further studies and the development of novel and powerful anti-cancer drugs.
Triterpenoids from the Leaves of Cyclocarya paliurus and Their Glucose Uptake Activity in 3T3-L1 Adipocytes
Authors: Liang Xiaoqin , Deng Shengping , Huang Yan , Pan Liwei , Chang Yanling , Hou Ping , Ren Chenyang , Xu Weifeng , Yang Ruiyun , Li Kanyuan , Li Jun , He Ruijie
Published: April 2023

Four new dammarane triterpenoid saponins cypaliurusides Z1–Z4 (1–4) and eight known analogs (5–12) were isolated from the leaves of Cyclocarya paliurus. The structures of the isolated compounds were determined using a comprehensive analysis of 1D and 2D NMR and HRESIMS data. The docking study demonstrated that compound 10 strongly bonded with PTP1B (a potential drug target for the treatment of type-II diabetes and obesity), hydrogen bonds, and hydrophobic interactions, verifying the importance of sugar unit. The effects of the isolates on insulin-stimulated glucose uptake in 3T3-L1 adipocytes were evaluated and three dammarane triterpenoid saponins (6, 7 and 10) were found to enhance insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Furthermore, compounds 6, 7, and 10 exhibited potent abilities to promote insulin-stimulated glucose uptake in 3T3-L1 adipocytes in a dose-dependent manner. Thus, the abundant dammarane triterpenoid saponins from C. paliurus leaves exhibited stimulatory effects on glucose uptake with application potential as a antidiabetic treatment.
Non-Volatile Compounds Involved in Bitterness and Astringency of Pulses: A Review
Authors: Karolkowski Adeline , Belloir Christine , Briand Loïc , Salles Christian
Published: April 2023

Despite the many advantages of pulses, they are characterised by off-flavours that limit their consumption. Off-notes, bitterness and astringency contribute to negative perceptions of pulses. Several hypotheses have assumed that non-volatile compounds, including saponins, phenolic compounds, and alkaloids, are responsible for pulse bitterness and astringency. This review aims to provide an overview highlighting the non-volatile compounds identified in pulses and their bitter and/or astringent characteristics to suggest their potential involvement in pulse off-flavours. Sensorial analyses are mainly used to describe the bitterness and astringency of molecules. However, in vitro cellular assays have shown the activation of bitter taste receptors by many phenolic compounds, suggesting their potential involvement in pulse bitterness. A better knowledge of the non-volatile compounds involved in the off-flavours should enable the creation of efficient strategies to limit their impact on overall perception and increase consumer acceptability.
An Imine-Based Porous 3D Covalent Organic Polymer as a New Sorbent for the Solid-Phase Extraction of Amphenicols from Water Sample
Authors: Wei Jinjian , Chen Lengbing , Zhang Rui , Yu Yi , Ji Wenhua , Hou Zhaosheng , Chen Yuqin , Zhang Zhide
Published: April 2023

In this paper, an imine-based porous 3D covalent organic polymer (COP) was synthesized via solvothermal condensation. The structure of the 3D COP was fully characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and powder X-ray diffractometry, thermogravimetric analysis, and Brunauer–Emmer–Teller (BET) nitrogen adsorption. This porous 3D COP was used as a new sorbent for the solid-phase extraction (SPE) of amphenicol drugs, including chloramphenicol (CAP), thiamphenicol (TAP), and florfenicol (FF) in aqueous solution. Factors were investigated for their effects on the SPE efficiency, including the types and volume of eluent, washing speed, pH, and salinity of water. Under the optimized conditions, this method gave a wide linear range (0.1–200 ng/mL) with a high correlation coefficient value (R2 > 0.99), low limits of detection (LODs, 0.01–0.03 ng/mL), and low limits of quantification (LOQs, 0.04–0.10 ng/mL). The recoveries ranged from 83.98% to 110.7% with RSDs ≤ 7.02%. The good enrichment performance for this porous 3D COP might contribute to the hydrophobic and π–π interactions, the size-matching effect, hydrogen bonding, and the good chemical stability of 3D COP. This 3D COP-SPE method provides a promising approach to selectively extract trace amounts of CAP, TAP, and FF in environmental water samples in ng quantities.
Fast and Selective Degradation of Biomass for Xylose, Glucose and Lignin under Mild Conditions
Authors: Zhang Shangzhong , Duan Yi , Teng Changchang , Quan Hongdong , Yang Xiuguo , Li Hongyan , Li Xiaohe , Yan Lifeng
Published: April 2023

The conversion of lignocellulose into valuable chemicals has been recognized as the key technology in green chemistry. However, selective degradation of hemicellulose and cellulose with the production of lignin is still a challenge. Therefore, a two-step process has been developed to degrade corncob into xylose and glucose under mild conditions. At first, the corncob was treated with the lower concentration of zinc chloride aqueous solution (30–55 w%) at 95 °C with a short reaction time (8–12 min) and 30.4 w% (selectivity = 89%) of xylose obtained with a solid residue of the composite of cellulose and lignin. Next, the solid residue was treated with a high concentration of zinc chloride aqueous solution (65–85 w%) at 95 °C for about 10 min, and 29.4 w% (selectivity = 92%) of glucose can be obtained. Combining the two steps, the total yield of xylose is 97%, while glucose is 95%. In addition, high pure lignin can be obtained simultaneously, which was confirmed using HSQC studies. Furthermore, for the solid residue of the first-step reaction, a ternary deep eutectic solvent (DES) (choline chloride/oxalic acid/1,4-butanediol, ChCl/OA/BD) has been used to separate the cellulose and lignin efficiently, and high-quality cellulose (Re-C) and lignin (Re-L) were obtained. Furthermore, it provides a simple method to disassemble the lignocellulose for monosaccharides, lignin, and cellulose.
Elucidating the Role of Noncovalent Interactions in Favipiravir, a Drug Active against Various Human RNA Viruses; a 1H-14N NQDR/Periodic DFT/QTAIM/RDS/3D Hirshfeld Surfaces Combined Study
Authors: Latosińska Jolanta Natalia , Latosińska Magdalena , Seliger Janez , Žagar Veselko , Apih Tomaž , Grieb Paweł
Published: April 2023

Favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide, FPV), an active pharmaceutical component of the drug discovered and registered in March 2014 in Japan under the name Avigan, with an indication for pandemic influenza, has been studied. The study of this compound was prompted by the idea that effective processes of recognition and binding of FPV to the nucleic acid are affected predominantly by the propensity to form intra- and intermolecular interactions. Three nuclear quadrupole resonance experimental techniques, namely 1H-14N cross-relaxation, multiple frequency sweeps, and two-frequency irradiation, followed by solid-state computational modelling (density functional theory supplemented by the quantum theory of atoms in molecules, 3D Hirshfeld Surfaces, and reduced density gradient) approaches were applied. The complete NQR spectrum consisting of nine lines indicating the presence of three chemically inequivalent nitrogen sites in the FPV molecule was detected, and the assignment of lines to particular sites was performed. The description of the nearest vicinity of all three nitrogen atoms was used to characterize the nature of the intermolecular interactions from the perspective of the local single atoms and to draw some conclusions on the nature of the interactions required for effective recognition and binding. The propensity to form the electrostatic N−H···O, N−H···N, and C−H···O intermolecular hydrogen bonds competitive with two intramolecular hydrogen bonds, strong O−H···O and very weak N−H···N, closing the 5-member ring and stiffening the structure, as well as π···π and F···F dispersive interactions, were analysed in detail. The hypothesis regarding the similarity of the interaction pattern in the solid and the RNA template was verified. It was discovered that the -NH2 group in the crystal participates in intermolecular hydrogen bonds N–H···N and N–H···O, in the precatalytic state only in N–H···O, while in the active state in N–H···N and N–H···O hydrogen bonds, which is of importance to link FVP to the RNA template. Our study elucidates the binding modes of FVP (in crystal, precatalytic, and active forms) in detail and should guide the design of more potent analogues targeting SARS-CoV-2. Strong direct binding of FVP-RTP to both the active site and cofactor discovered by us suggests a possible alternative, allosteric mechanism of FVP action, which may explain the scattering of the results of clinical trials or the synergistic effect observed in combined treatment against SARS-CoV-2.
In Silico Exploration of Alternative Conformational States of VDAC
Authors: Mannella Carmen
Published: April 2023

VDAC (Voltage-Dependent Anion-selective Channel) is the primary metabolite pore in the mitochondrial outer membrane (OM). Atomic structures of VDAC, consistent with its physiological “open” state, are β-barrels formed by 19 transmembrane (TM) β-strands and an N-terminal segment (NTERM) that folds inside the pore lumen. However, structures are lacking for VDAC’s partially “closed” states. To provide clues about possible VDAC conformers, we used the RoseTTAFold neural network to predict structures for human and fungal VDAC sequences modified to mimic removal from the pore wall or lumen of “cryptic” domains, i.e., segments buried in atomic models yet accessible to antibodies in OM-bound VDAC. Predicted in vacuo structures for full-length VDAC sequences are 19-strand β-barrels similar to atomic models, but with weaker H-bonding between TM strands and reduced interactions between NTERM and the pore wall. Excision of combinations of “cryptic” subregions yields β-barrels with smaller diameters, wide gaps between N- and C-terminal β-strands, and in some cases disruption of the β-sheet (associated with strained backbone H-bond registration). Tandem repeats of modified VDAC sequences also were explored, as was domain swapping in monomer constructs. Implications of the results for possible alternative conformational states of VDAC are discussed.
Development of a Highly Sensitive Hybrid LC/MS Assay for the Quantitative Measurement of CTLA-4 in Human T Cells
Authors: Wei Dong , Horton Kristin L. , Chen John , Dong Linlin , Chen Susan , Abdul-Hadi Kojo , Zhang Ting Ting , Casson Cierra N. , Shaw Michael , Shiraishi Tsubasa , Wilkinson Brandon , Ji Chengjie , Qian Mark G.
Published: April 2023

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a check point protein expressed on the surface of T cells and plays a central role in regulating the immune response. In recent years, CTLA-4 has become a popular target for cancer immunotherapy in which blocking CTLA-4 can restore T-cell function and enhance the immune response against cancer. Currently, there are many CTLA-4 inhibitors in a variety of modalities, including cell therapies, which are being developed in both preclinical and clinical stages to further harness the potential of the target for the treatment of certain types of cancer. In drug discovery research, measuring the level of CTLA-4 in T cells is important for drug discovery and development because it provides key information for quantitative assessment of the pharmacodynamics, efficacy, and safety of the CTLA-4-based therapies. However, to our best knowledge, there is still no report of a sensitive, specific, accurate, and reliable assay for CTLA-4 measurement. In this work, an LC/MS-based method was developed to measure CTLA-4 in human T cells. The assay demonstrated high specificity with an LLOQ of 5 copies of CTLA-4 per cell when using 2.5 million T cells for analysis. As shown in the work, the assay was successfully used to measure CTLA-4 levels in subtype T-cell samples from individual healthy subjects. The assay could be applied in supporting the studies of CTLA-4-based cancer therapies.
Remediation of Surfactants Used by VUV/O3 Techniques: Degradation Efficiency, Pathway and Toxicological Analysis
Authors: Li Hang , Yang Yanling , Li Xing , Ullah Habib
Published: April 2023

Surfactants are increasingly used in systems that come into contact with the human body, such as food, pharmaceuticals, cosmetics and personal hygiene products. Increasing attention is being devoted to the toxic effects of surfactants in various human contact formulations, as well as the removal of residual surfactants. In the presence of ozone (O3), anion surfactants—a characteristic micro-pollutant—such as sodium dodecylbenzene sulfonate (SDBS) in greywater, can be removed using radical advanced oxidation. Herein, we report a systematic study of the SDBS degradation effect of O3 activated by vacuum ultraviolet (VUV) irradiation and the influence of water composition on VUV/O3, and determined the contribution of radical species. We show a synergistic effect of VUV and O3, while VUV/O3 reached a higher mineralization (50.37%) than that of VUV (10.63%) and O3 (29.60%) alone. The main reactive radicals of VUV/O3 were HO•. VUV/O3 had an optimal pH of 9. The addition of SO42− had almost no effect on the degradation of SDBS by VUV/O3, Cl− and HCO3− slightly reduced the reaction rate, and NO3− had a significant inhibition on the degradation. In total, SDBS had three isomers, with which the three degradation pathways were very comparable. Compared with SDBS, the toxicity and harmfulness of the degradation by-products of the VUV/O3 process decreased. Additionally, VUV/O3 could degrade synthetic anion surfactants from laundry greywater effectively. Overall, the results show the potential of VUV/O3 in safeguarding humans from residual surfactant hazards.
Biosorption of Triphenyl Methane Dyes (Malachite Green and Crystal Violet) from Aqueous Media by Alfa (Stipa tenacissima L.) Leaf Powder
Authors: Ouettar Lamia , Guechi El-Khamssa , Hamdaoui Oualid , Fertikh Nadia , Saoudi Fethi , Alghyamah Abudulaziz
Published: April 2023

This study includes the characterization and exploitation of an abundant agricultural waste in Algeria, Alfa (Stipa tenacissima L.) leaf powder (ALP) as a biosorbent for the removal of hazardous triphenylmethane dyes, malachite green (basic green 4) and crystal violet (basic violet 3), from aqueous media under various operating conditions in batch mode. The effect of experimental parameters such as initial dye concentration (10–40 mg/L), contact time (0–300 min), biosorbent dose (2.5–5.5 g/L), initial pH (2–8), temperature (298–328 K), and ionic strength on dye sorption was investigated. The results of both dyes show that the increase in initial concentration, contact time, temperature, and initial pH of solution leads to an increase in biosorbed quantity, unlike the effect of ionic strength. The biosorption kinetics for triphenylmethane dyes on ALP was analyzed by pseudo-first-order, pseudo-second-order, Elovich, and intraparticle diffusion models proposed by the Weber–Morris equation. Equilibrium sorption data were analyzed by six isotherms, namely the Langmuir, Freundlich, Harkins–Jura, Flory–Huggins, Elovich, and Kiselev isotherms. The thermodynamic parameters were evaluated for both dyes. The thermodynamic results suggest that both dyes’ biosorption is a typical physical process, spontaneous and endothermic in nature.
Systematic Theoretical Study on the pH-Dependent Absorption and Fluorescence Spectra of Flavins
Authors: Wang Jinyu , Liu Yajun
Published: April 2023

Flavins are a class of organic compounds with the basic structure of 7,8-dimethy-10-alkyl isoalloxazine. They are ubiquitous in nature and participate in many biochemical reactions. Due to various existing forms, there is a lack of systematic research on the absorption and fluorescence spectra of flavins. In this study, employing the density functional theory (DFT) and time-dependent (TD) DFT, we calculated the pH-dependent absorption and fluorescence spectra of flavin of three redox states (quinone, semiquinone, and hydroquinone) in solvents. The chemical equilibrium of three redox states of flavins and the pH effect on the absorption spectra and fluorescence spectra of flavins were carefully discussed. The conclusion helps with identifying the existing forms of flavins in solvent with different pH values.
Simple Synthetic Approach to N-(Pyridin-2-yl)imidates from Nitrostyrenes and 2-Aminopyridines via the N-(Pyridin-2-yl)iminonitriles as Intermediates
Authors: Chaidali Andriani G. , Lykakis Ioannis N.
Published: April 2023

A facile, green, synthetic protocol of several substituted N-(pyridin-2-yl)imidates from nitrostyrenes and 2-aminopyridines via the corresponding N-(pyridin-2-yl)iminonitriles as intermediates is reported. The reaction process involved the in situ formation of the corresponding α-iminontriles under heterogeneous Lewis acid catalysis in the presence of Al2O3. Subsequently, α-iminonitriles were selectively transformed into the desired N-(pyridin-2-yl)imidates under ambient conditions and in the presence of Cs2CO3 in alcoholic media. Under these conditions, 1,2- and 1,3-propanediols also led to the corresponding mono-substituted imidates at room temperature. The present synthetic protocol was also developed on one mmol scale, providing access to this important scaffold. A preliminary synthetic application of the present N-(pyridin-2-yl)imidates was carried out for their facile conversion into the N-heterocycles 2-(4-chlorophenyl)-4,5-dihydro-1H-imidazole and 2-(4-chlorophenyl)-1,4,5,6-tetrahydropyrimidine in the presence of the corresponding ethylenediamine and 1,3-diaminopropane.