bluuebunny/crossref_metadata_2025 huggingface dataset:
The Analysis of Energy Recovered during the Braking of an Electric Vehicle in Different Driving Conditions
Authors: Szumska Emilia M. , Jurecki Rafał
Published: December 2022

The partial recovery of kinetic energy during braking allows the vehicle’s battery to be additionally charged and thus extends the range of an electric vehicle. Because of the different operating strategies of the braking energy recovery system, it is important to understand the factors influencing the level of recovered energy. The driving conditions at the place of use have a direct impact on the energy efficiency of an electric vehicle. The purpose of this paper was to analyze the energy recovered during braking in different driving conditions. The tests were based on the parameters of actual trips made along urban and suburban routes, and express roads. The collected actual speed profiles were used for the simulation studies. AVL cruise vehicle simulation software was used in the study. Simulation tests revealed that the levels of energy recovered during braking in an electric vehicle were the highest in urban conditions. The amount of energy recovered during urban driving can account for 20% of the total trip energy. In driving conditions characterized by different intensities caused by trips at different times of the day, similar values of recovered energy were recorded. When driving in the afternoon hours, the level of recovered energy per 1 km was about 2% lower than when driving in rush hour conditions. From the results presented in this paper, it can be concluded that driving conditions have an impact on the level of recovered energy. The type of road on which the electric vehicle drives is particularly important.
Market Integration, Industrial Structure, and Carbon Emissions: Evidence from China
Authors: Zheng Kun , Deng Hongbing , Lyu Kangni , Yang Shuang , Cao Yu
Published: December 2022

Against the backdrop of China’s carbon emission reduction targets and the promotion of the construction of a unified domestic market, what kind of carbon emission effect has market integration had in weakening regional barriers and optimizing resource allocation? This paper adopts a two-way fixed effects analysis based on China’s provincial panel data from 2003 to 2019. It uses a mediation model to explore the relationship between market integration and carbon emissions. Furthermore, industrial rationalization and upgrade are the basis for examining whether a competitive or cooperative relationship exists between the carbon emission effects generated and promoting market integration between regions. The study finds a negative relationship between market integration and carbon emissions. In addition, there is significant heterogeneity in the effect of market integration on carbon emissions, and the influence effect is mainly in central China; industrial rationalization can play an enhanced role in the process of the negative impact of market integration on carbon emissions, further enhancing the negative contribution of market integration to carbon emissions. However, market integration can weaken its negative impact on carbon emissions with the industrial upgrade, and there may still be invisible barriers between regions in promoting market integration barriers.
Extraction and Performance Analysis of Hydrocarbons from Waste Plastic Using the Pyrolysis Process
Authors: Ramesh B. T. , Sayyad Javed , Bongale Arunkumar , Bongale Anupkumar
Published: December 2022

Ecosystem destruction is one of today’s significant challenges due to fast industrialisation and an increasing population. It takes several years for solid trash, such as plastic bottles and super-market bags, to decompose in nature. In addition, plastic disposal techniques such as landfilling, reuse, and incineration pose significant threats to human health and the environment. In this paper, we investigated whether the impact of mixing biodiesel with waste oil from recycled plastic on the resulting fuel mixture’s yields better physical and chemical properties. Consequently, pyrolysis is one of the most advantageous and practical waste disposal methods as it is both environmentally benign and efficient. Pyrolysis is the high-temperature thermal breakdown of solid waste to produce pyrolytic oil. The pyrolytic (plastic) oil produced is converted to a hydrocarbon-rich pyrolytic fuel. Similar to diesel and gasoline, pyrolytic fuel has the same calorific value. Internal combustion engines may operate on pyrolytic fuel without suffering a performance reduction. Researchers examined engine performance and exhaust pollutants. The research discovered that the engine could operate on plastic pyrolysis fuel at full load, enhance brake thermal efficiency by 6–8%, and lower UBHC and CO emissions; however, nitrous oxide (NOx) emissions were noticeably higher. The findings demonstrated the possibility of using plastic pyrolysis fuel as a diesel substitute.
Condition Assessment of Gas Insulated Switchgear Using Health Index and Conditional Factor Method
Authors: Panmala Nattapon , Suwanasri Thanapong , Suwanasri Cattareeya
Published: December 2022

This paper proposes a comprehensive procedure to assess the condition of gas insulated switchgear (GIS) equipment by using the conventional weight and score method and introducing a conditional factor to improve the accuracy of the health index evaluation. Generally, the inspection and testing of GIS components are conducted according to manufacturer recommendations and guidelines in the international standards. However, this raw data has not been simplified and systematically processed for condition assessment. The score and weight technique are applied to transform the physical condition according to visible and measurable aging to numerical values in terms of component and bay health index values. The accuracy of the obtained health index has been improved by a conditional factor, which considers invisible aging factors, such as age, number of switching operations, degree of satisfactory operation, obsolescence, and adequacy of the interrupting rating. Here, a condition evaluation procedure has been developed and compared with the fuzzy logic method and the health index dominant score technique with satisfactory results. Subsequently, the proposed procedure has been developed as web application software to evaluate 175 bays of GIS in both 115 and 230 kV networks of an independent power producer supplying electricity of 3094 MW to a large industrial estate in Thailand. Eight GIS bays showed moderate or poor condition and the proper actions were assigned to prevent their failure. The software is in use in practice as a decision support tool to effectively manage the maintenance tasks and to improve supply reliability.
Synergistic Enhancement Effect of Compound Additive of Organic Alcohols and Biosurfactant on Enzymatic Hydrolysis of Lignocellulose
Authors: Liang Cuiyi , Feng Qifa , Lu Si , Wang Qiong , Hu Yunzi , Wang Zhongming , Wang Wen , Qi Wei
Published: December 2022

The insufficient of lignocellulose degradation enzymes, such as cellulase and hemicellulase, is the major obstacle that hinders the bioconversion of lignocellulosic biomass to monosaccharides, especially during the woody biomass hydrolysis process. The addition of additives has received significant attention due to their enhancement of the enzymatic degradation efficiency of lignocellulose. In the present study, a combination of organic alcohols and a biosurfactant could synergistically enhance the saccharification of the cellulose substrate of Avicel, as well as that of pretreated poplar. Results showed that compound additives can greatly improve the conversion rate of enzymatic hydrolysis. The combination of 0.1% (v/v) n-decanol and 1% (v/v) sophorolipid dramatically increased the poplar enzymatic conversion rate from 17.9% to 85%, improving it by 67.1%. Enzyme-rich Hypocrea sp. W63 was fermented to obtain beta-glucosidase (BGL) and xylanase (XYL), which were used as auxiliary enzymes during enzymatic hydrolysis. It was found that the effects of such a combination of additives improved the filter paper activity, stability, and longevity, helping in the recovery of the cellulase cocktail. The compound additives associated with the commercial cellulase and Hypocrea sp. W63 enzyme solution formed an excellent formula for improving the stability of BGL and XYL. The results provide insight into compound additives and the use of a cellulase and auxiliary enzyme cocktail to improve enzymatic hydrolysis for lignocellulose conversion into biofuels.
Click Chemistry of Selenium Dihalides: Novel Bicyclic Organoselenium Compounds Based on Selenenylation/Bis-Functionalization Reactions and Evaluation of Glutathione Peroxidase-like Activity
Authors: Musalov Maxim V. , Potapov Vladimir A.
Published: December 2022

A number of highly efficient methods for the preparation of novel derivatives of 9-selenabicyclo[3.3.1]nonane in high yields based on selenium dibromide and cis,cis-1,5-cyclooctadiene are reported. The one-pot syntheses of 2,6-diorganyloxy-9-selenabicyclo[3.3.1]nonanes using various O-nucleophiles including alkanols, phenols, benzyl, allyl, and propargyl alcohols were developed. New 2,6-bis(1,2,3-triazol-1-yl)-9-selenabicyclo[3.3.1]nonanes were obtained by the copper-catalyzed 1,3-dipolar cycloaddition of 2,6-diazido-9-selenabicyclo[3.3.1]nonane with unsubstituted gaseous acetylene and propargyl alcohol. The synthesis of 2,6-bis(vinylsulfanyl)-9-selenabicyclo[3.3.1]nonane, based on the generation of corresponding dithiolate anion from bis[amino(iminio)methylsulfanyl]-9-selenabicyclo[3.3.1]nonane dibromide, followed by the nucleophilic addition of the dithiolate anion to unsubstituted acetylene, was developed. The glutathione peroxidase-like activity of the obtained water-soluble products was estimated and compounds with high activity were found. Overall, 2,6-Diazido-9-selenabicyclo[3.3.1]nonane exhibits the highest activity among the obtained compounds.
Interplay between Serotonin, Immune Response, and Intestinal Dysbiosis in Inflammatory Bowel Disease
Authors: González Delgado Samantha , Garza-Veloz Idalia , Trejo-Vazquez Fabiola , Martinez-Fierro Margarita L
Published: December 2022

Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal disorder characterized by periods of activity and remission. IBD includes Crohn’s disease (CD) and ulcerative colitis (UC), and even though IBD has not been considered as a heritable disease, there are genetic variants associated with increased risk for the disease. 5-Hydroxytriptamine (5-HT), or serotonin, exerts a wide range of gastrointestinal effects under both normal and pathological conditions. Furthermore, Serotonin Transporter (SERT) coded by Solute Carrier Family 6 Member 4 (SLC6A4) gene (located in the 17q11.1-q12 chromosome), possesses genetic variants, such as Serotonin Transporter Gene Variable Number Tandem Repeat in Intron 2 (STin2-VNTR) and Serotonin-Transporter-linked promoter region (5-HTTLPR), which have an influence over the functionality of SERT in the re-uptake and bioavailability of serotonin. The intestinal microbiota is a crucial actor in normal human gut physiology, exerting effects on serotonin, SERT function, and inflammatory processes. As a consequence of abnormal serotonin signaling and SERT function under these inflammatory processes, the use of selective serotonin re-uptake inhibitors (SSRIs) has been seen to improve disease activity and extraintestinal manifestations, such as depression and anxiety. The aim of this study is to integrate scientific data linking the intestinal microbiota as a regulator of gut serotonin signaling and re-uptake, as well as its role in the pathogenesis of IBD. We performed a narrative review, including a literature search in the PubMed database of both review and original articles (no date restriction), as well as information about the SLC6A4 gene and its genetic variants obtained from the Ensembl website. Scientific evidence from in vitro, in vivo, and clinical trials regarding the use of selective serotonin reuptake inhibitors as an adjuvant therapy in patients with IBD is also discussed. A total of 194 articles were used between reviews, in vivo, in vitro studies, and clinical trials.
Neuronal Calcium Sensor-1 Protects Cortical Neurons from Hyperexcitation and Ca2+ Overload during Ischemia by Protecting the Population of GABAergic Neurons
Authors: Varlamova Elena G. , Plotnikov Egor Y. , Turovsky Egor A.
Published: December 2022

A defection of blood circulation in the brain leads to ischemia, damage, and the death of nerve cells. It is known that individual populations of GABAergic neurons are the least resistant to the damaging factors of ischemia and therefore they die first of all, which leads to impaired inhibition in neuronal networks. To date, the neuroprotective properties of a number of calcium-binding proteins (calbindin, calretinin, and parvalbumin), which are markers of GABAergic neurons, are known. Neuronal calcium sensor-1 (NCS-1) is a signaling protein that is expressed in all types of neurons and is involved in the regulation of neurotransmission. The role of NCS-1 in the protection of neurons and especially their individual populations from ischemia and hyperexcitation has not been practically studied. In this work, using the methods of fluorescence microscopy, vitality tests, immunocytochemistry, and PCR analysis, the molecular mechanisms of the protective action of NCS-1 in ischemia/reoxygenation and hyperammonemia were established. Since NCS-1 is most expressed in GABAergic neurons, the knockdown of this protein with siRNA led to the most pronounced consequences in GABAergic neurons. The knockdown of NCS-1 (NCS-1-KD) suppressed the basic expression of protective proteins without significantly reducing cell viability. However, ischemia-like conditions (oxygen-glucose deprivation, OGD) and subsequent 24-h reoxygenation led to a more massive activation of apoptosis and necrosis in neurons with NCS-1-KD, compared to control cells. The mass death of NCS-1-KD cells during OGD and hyperammonemia has been associated with the induction of a more pronounced network hyperexcitation symptom, especially in the population of GABAergic neurons, leading to a global increase in cytosolic calcium ([Ca2+]i). The symptom of hyperexcitation of neurons with NCS-1-KD correlated with a decrease in the level of expression of the calcium-binding protein-parvalbumin. This was accompanied by an increase in the expression of excitatory ionotropic glutamate receptors, N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (NMDAR and AMPAR) against the background of suppression of the expression of glutamate decarboxylase (synthesis of γ-aminobutyric acid).
Soybean CALCIUM-DEPENDENT PROTEIN KINASE17 Positively Regulates Plant Resistance to Common Cutworm (Spodoptera litura Fabricius)
Authors: Wang Huiqi , Li Xiao , Su Fenglin , Liu Hailun , Hu Dezhou , Huang Fang , Yu Deyue , Wang Hui
Published: December 2022

Soybean is frequently attacked by herbivorous pests throughout the growth period. Exploring anti-insect genes to improve insect resistance in soybean is an important soybean breeding goal. Here, we cloned and characterized the gene for a quantitative trait locus (QTL) related to insect resistance, Glyma.06g189600, which encodes CALCIUM-DEPENDENT PROTEIN KINASE17 (GmCDPK17) in soybean. The pairwise sequence alignment analysis revealed that the presumed protein of GmCDPK17 shares 52.06% similarity with that of GmCDPK38, a known negative regulatory gene of insect resistance in soybean. Ectopic expression of GmCDPK17 and GmCDPK38 restored the phenotypes of the Arabidopsis insect-susceptible mutant cpk10 and insect-resistant mutant cpk28, respectively. Moreover, transgenic hairy roots of the soybean cultivar Jack were generated by Agrobacterium-mediated transformation. Overexpression of GmCDPK17 increased soybean hairy root resistance to common cutworm (CCW), while RNA interference of the gene decreased soybean hairy root resistance to CCW. Sequencing data from the cultivated and wild soybeans were used to analyze the genetic diversity of GmCDPK17. This gene was subjected to domestication selection. Six and seven haplotypes (Haps) were identified in cultivated and wild soybeans, respectively. The resistance Hap1 is not widely used in cultivated soybeans and is mainly distributed at low latitudes. Accessions with resistance haplotypes of the GmCDPK17 and GmCDPK38 genes showed high resistance to CCW. Altogether, we revealed a novel positive regulatory insect resistance gene, GmCDPK17, which may further improve insect resistance in soybean.
Screening Key Genes and Biological Pathways in Nasopharyngeal Carcinoma by Integrated Bioinformatics Analysis
Authors: Tai Junhu , Park Jaehyung , Han Munsoo , Kim Tae Hoon
Published: December 2022

The purpose of this study was to identify the hub genes and biological pathways of nasopharyngeal carcinoma (NPC) through bioinformatics analysis and potential new therapeutic targets. In this study, three datasets were downloaded from the Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) between NPC and normal tissues were analyzed using the GEO2R online tool. Volcano and heat maps of the DEGs were visualized using the hiplot database. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the upregulated and downregulated DEGs were performed using the DAVID database. Finally, we established a protein-protein interaction (PPI) network using the STRING database and showed the differential expression of hub genes between the normal and tumor tissues. In all, 109,371,221 upregulated DEGs and 139,226,520 downregulated DEGs were obtained in datasets GSE40290, GSE61218, and GSE53819, respectively, and 18 common differential genes, named co-DEGs, were screened in the three datasets. The most abundant biological GO terms of the co-DEGs were inflammatory response et al. The KEGG pathway enrichment analysis showed that co-DEGs mainly participated in the interleukin (IL)-17 signaling pathway et al. Finally, we identified four hub genes using PPI analysis and observed that three of them were highly expressed in tumor tissues. In this study, the hub genes of NPC, such as PTGS2, and pathways such as IL-17 signaling, were identified through bioinformatics analysis, which may be potential new therapeutic targets for NPC.
Magnetic Luffa-Leaf-Derived Hierarchical Porous Biochar for Efficient Removal of Rhodamine B and Tetracycline Hydrochloride
Authors: Su Yingjie , Zheng Yangyang , Feng Meiqin , Chen Siji
Published: December 2022

Luffa leaf (LL) is an agricultural waste produced by loofah. In this work, LL was used as biomass carbon source for biochars for the first time. After carbonization, activation, and chemical co-precipitation treatments, a magnetic lignocellulose-derived hierarchical porous biochar was obtained. The specific surface area and total pore volume were 2565.4 m2/g and 1.4643 cm3/g, and the surface was rich in carbon and oxygen functional groups. The synthetic dye rhodamine B (RhB) and the antibiotic tetracycline hydrochloride (TH) were selected as organic pollutant models to explore the ability to remove organic pollutants, and the results showed good adsorption performances. The maximum adsorption capacities were 1701.7 mg/g for RhB and 1755.9 mg/g for TH, which were higher than most carbon-based adsorbents. After 10 cycles of use, the removal efficiencies were still maintained at more than 70%, showing good stability. This work not only verified the feasibility of lignocellulose LL as a carbon source to prepare biochar but also prepared a magnetic hierarchical porous adsorbent with good performances that can better treat RhB and TH, which provided a new idea and direction for the efficient removal of organic pollutants in water.
Manganese Stress Tolerance Depends on Yap1 and Stress-Activated MAP Kinases
Authors: de Oya Inés G. , Jiménez-Gutiérrez Elena , Gaillard Hélène , Molina María , Martín Humberto , Wellinger Ralf Erik
Published: December 2022

Understanding which intracellular signaling pathways are activated by manganese stress is crucial to decipher how metal overload compromise cellular integrity. Here, we unveil a role for oxidative and cell wall stress signaling in the response to manganese stress in yeast. We find that the oxidative stress transcription factor Yap1 protects cells against manganese toxicity. Conversely, extracellular manganese addition causes a rapid decay in Yap1 protein levels. In addition, manganese stress activates the MAPKs Hog1 and Slt2 (Mpk1) and leads to an up-regulation of the Slt2 downstream transcription factor target Rlm1. Importantly, Yap1 and Slt2 are both required to protect cells from oxidative stress in mutants impaired in manganese detoxification. Under such circumstances, Slt2 activation is enhanced upon Yap1 depletion suggesting an interplay between different stress signaling nodes to optimize cellular stress responses and manganese tolerance.
Impact of Troponin in Cardiomyopathy Development Caused by Mutations in Tropomyosin
Authors: Nefedova Victoria V. , Kopylova Galina V. , Shchepkin Daniil V. , Kochurova Anastasia M. , Kechko Olga I. , Borzova Vera A. , Ryabkova Natalia S. , Katrukha Ivan A. , Mitkevich Vladimir A. , Bershitsky Sergey Y. , Levitsky Dmitrii I. , Matyushenko Alexander M.
Published: December 2022

Tropomyosin (Tpm) mutations cause inherited cardiac diseases such as hypertrophic and dilated cardiomyopathies. We applied various approaches to investigate the role of cardiac troponin (Tn) and especially the troponin T (TnT) in the pathogenic effects of Tpm cardiomyopathy-associated mutations M8R, K15N, A277V, M281T, and I284V located in the overlap junction of neighboring Tpm dimers. Using co-sedimentation assay and viscosity measurements, we showed that TnT1 (fragment of TnT) stabilizes the overlap junction of Tpm WT and all Tpm mutants studied except Tpm M8R. However, isothermal titration calorimetry (ITC) indicated that TnT1 binds Tpm WT and all Tpm mutants similarly. By using ITC, we measured the direct KD of the Tpm overlap region, N-end, and C-end binding to TnT1. The ITC data revealed that the Tpm C-end binds to TnT1 independently from the N-end, while N-end does not bind. Therefore, we suppose that Tpm M8R binds to TnT1 without forming the overlap junction. We also demonstrated the possible role of Tn isoform composition in the cardiomyopathy development caused by M8R mutation. TnT1 dose-dependently reduced the velocity of F-actin-Tpm filaments containing Tpm WT, Tpm A277V, and Tpm M281T mutants in an in vitro motility assay. All mutations impaired the calcium regulation of the actin–myosin interaction. The M281T and I284V mutations increased the calcium sensitivity, while the K15N and A277V mutations reduced it. The Tpm M8R, M281T, and I284V mutations under-inhibited the velocity at low calcium concentrations. Our results demonstrate that Tpm mutations likely implement their pathogenic effects through Tpm interaction with Tn, cardiac myosin, or other protein partners.
Influence of Calcium Resonance-Tuned Low-Frequency Magnetic Fields on Daphnia magna
Authors: Krylov Viacheslav V. , Papchenkova Galina A. , Golovanova Irina L.
Published: December 2022

A biophysical model for calculating the effective parameters of low-frequency magnetic fields was developed by Lednev based on summarized empirical data. According to this model, calcium ions as enzyme cofactors can be the primary target of low-frequency magnetic fields with different parameters tuned to calcium resonance. However, the effects of calcium-resonant combinations of static and alternating magnetic fields that correspond to Lednev’s model and differ by order in frequency and intensity were not studied. It does not allow for confidently discussing the primary targets of low-frequency magnetic fields in terms of the magnetic influence on ions-enzyme cofactors. To clarify this issue, we examined the response of freshwater crustaceans Daphnia magna to the impact of combinations of magnetic fields targeted to calcium ions in enzymes according to Lednev’s model that differ in order of magnitude. Life-history traits and biochemical parameters were evaluated. Exposure of daphnids to both combinations of magnetic fields led to a long-term delay of the first brood release, an increase in the brood size, a decrease in the number of broods, and the period between broods. The amylolytic activity, proteolytic activity, and sucrase activity significantly decreased in whole-body homogenates of crustaceans in response to both combinations of magnetic fields. The similarity in the sets of revealed effects assumes that different magnetic fields tuned to calcium ions in biomolecules can affect the same primary molecular target. The results suggest that the low-frequency magnetic fields with parameters corresponding to Lednev’s model of interaction between biological molecules and ions can remain effective with a significant decrease in the static magnetic background.
Crossing the Borders of Nanomedicine
Authors: Magro Massimiliano
Published: December 2022

Nanomedicine, being pressured by the increasing demands for fighting menacing diseases such as cancer, relies pragmatically on consolidated knowledge, namely on therapeutic strategies that are at an advanced stage of experimentation [...]
Structural, Thermodynamic and Enzymatic Characterization of N,N-Diacetylchitobiose Deacetylase from Pyrococcus chitonophagus
Authors: Biniek-Antosiak Katarzyna , Bejger Magdalena , Śliwiak Joanna , Baranowski Daniel , Mohammed Ahmed S. A. , Svergun Dmitri I. , Rypniewski Wojciech
Published: December 2022

Chitin is a major source of energy and macroelements for many organisms. An important step in its degradation is the deacetylation of chitin or its fragments. Deacetylase from the extremophile Pyrococcus chitonophagus has been analyzed by X-ray crystallography, small-angle X-ray scattering, differential scanning calorimetry, isothermal titration calorimetry and NMR to determine its structure, thermodynamics and enzymatic properties. It is a hexameric, zinc-containing metalloenzyme that retains its structural integrity up to temperatures slightly exceeding 100 °C. It removes the acetyl group specifically from the non-reducing end of the sugar substrate. Its main substrate is N,N-diacetylchitobiose but it also active, at a reduced level, toward N-acetyl-d-glucosamine or a trimer of N-acetyl-d-glucosamine units. Crystallographic analysis includes the structure of the enzyme with its main substrate approaching the active site in a monodentate manner, replacing the single water molecule that is bound at the Zn2+ cation when the ligand is absent. The Zn2+ cation remains tetrahedrally coordinated, with three of its ligands provided by the protein’s conserved His-Asp-His triad. The crystal structures are consistent with the reaction mechanism proceeding via an anhydride intermediate. Hydrolysis as the first step cannot be ruled out in a hydrated environment but no defined ‘hydrolytic water’ site can be identified in the analyzed structures.
Nanomaterials for Delivering Antibiotics in the Therapy of Pneumonia
Authors: Tang Jie , Ouyang Qiuhong , Li Yanyan , Zhang Peisen , Jin Weihua , Qu Shuang , Yang Fengmei , He Zhanlong , Qin Meng
Published: December 2022

Bacterial pneumonia is one of the leading causes of death worldwide and exerts a significant burden on health-care resources. Antibiotics have long been used as first-line drugs for the treatment of bacterial pneumonia. However, antibiotic therapy and traditional antibiotic delivery are associated with important challenges, including drug resistance, low bioavailability, and adverse side effects; the existence of physiological barriers further hampers treatment. Fortunately, these limitations may be overcome by the application of nanotechnology, which can facilitate drug delivery while improving drug stability and bioavailability. This review summarizes the challenges facing the treatment of bacterial pneumonia and also highlights the types of nanoparticles that can be used for antibiotic delivery. This review places a special focus on the state-of-the-art in nanomaterial-based approaches to the delivery of antibiotics for the treatment of pneumonia.
Gene Expression Linked to Reepithelialization of Human Skin Wounds
Authors: Ågren Magnus S. , Litman Thomas , Eriksen Jens Ole , Schjerling Peter , Bzorek Michael , Gjerdrum Lise Mette Rahbek
Published: December 2022

Our understanding of the regulatory processes of reepithelialization during wound healing is incomplete. In an attempt to map the genes involved in epidermal regeneration and differentiation, we measured gene expression in formalin-fixed, paraffin-embedded standardized epidermal wounds induced by the suction-blister technique with associated nonwounded skin using NanoString technology. The transcripts of 139 selected genes involved in clotting, immune response to tissue injury, signaling pathways, cell adhesion and proliferation, extracellular matrix remodeling, zinc transport and keratinocyte differentiation were evaluated. We identified 22 upregulated differentially expressed genes (DEGs) in descending order of fold change (MMP1, MMP3, IL6, CXCL8, SERPINE1, IL1B, PTGS2, HBEGF, CXCL5, CXCL2, TIMP1, CYR61, CXCL1, MMP12, MMP9, HGF, CTGF, ITGB3, MT2A, FGF7, COL4A1 and PLAUR). The expression of the most upregulated gene, MMP1, correlated strongly with MMP3 followed by IL6 and IL1B. rhIL-1β, but not rhIL-6, exposure of cultured normal human epidermal keratinocytes and normal human dermal fibroblasts increased both MMP1 mRNA and MMP-1 protein levels, as well as TIMP1 mRNA levels. The increased TIMP1 in wounds was validated by immunohistochemistry. The six downregulated DEGs (COL7A1, MMP28, SLC39A2, FLG1, KRT10 and FLG2) were associated with epidermal maturation. KLK8 showed the strongest correlation with MKI67 mRNA levels and is a potential biomarker for keratinocyte proliferation. The observed gene expression changes correlate well with the current knowledge of physiological reepithelialization. Thus, the gene expression panel described in this paper could be used in patients with impaired healing to identify possible therapeutic targets.
Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate
Authors: Kumari Sindhia , Khan Faisal , Siddiqui Amna Jabbar , Adil Nurmeen , Uddin Jalal , Asmari Mufarreh , Musharraf Syed Ghulam
Published: December 2022

β-thalassemia is one of the most common monogenic disorders and a life-threatening health issue in children. A cost-effective and safe therapeutic approach to treat this disease is to reactivate the γ-globin gene for fetal hemoglobin (HbF) production that has been silenced during infancy. Hydroxyurea (HU) is the only FDA approved HbF inducer. However, its cytotoxicity and inability to respond significantly in all patients pose a need for an HbF inducer with better efficacy. The study describes the serum metabolic alteration in β-YAC transgenic mice treated with Tenofovir disoproxil fumarate (TDF) (n = 5), a newly identified HbF inducer, and compared to the mice groups treated with HU (n = 5) and untreated control (n = 5) using gas chromatography-mass spectrometry. Various univariate and multivariate statistical analyses were performed to identify discriminant metabolites that altered the biological pathways encompassing galactose metabolism, lactose degradation, and inositol. Furthermore, the decreased concentrations of L-fucose and geraniol in TDF-treated mice help in recovering towards normal, decreasing oxidative stress even much better than the HU-treated mice. The proposed study suggested that TDF can reduce the deficiency of blood required for β-thalassemia and can be used for the preclinical study at phase I/II for fetal hemoglobin production.
Enhanced Therapeutic Effect of Optimized Melittin-dKLA, a Peptide Agent Targeting M2-like Tumor-Associated Macrophages in Triple-Negative Breast Cancer
Authors: Kim Soyoung , Choi Ilseob , Han Ik-Hwan , Bae Hyunsu
Published: December 2022

Triple-negative breast cancer (TNBC) is characterized by a high possibility of metastasis. M2-like tumor-associated macrophages (TAMs) are the main components of the tumor microenvironment (TME) and play a key role in TNBC metastasis. Therefore, TAMs may be a potential target for reducing TNBC metastasis. Melittin-dKLA, a peptide composed of fused melittin and pro-apoptotic peptide d(KLAKLAK)2 (dKLA), showed a potent therapeutic effect against cancers by depleting TAMs. However, melittin has a strong adverse hemolytic effect. Hence, we attempted to improve the therapeutic potential of melittin-dKLA by reducing toxicity and increasing stability. Nine truncated melittin fragments were synthesized and examined. Of the nine peptides, the melittin-dKLA8-26 showed the best binding properties to M2 macrophages and discriminated M0/M1/M2. All fragments, except melittin, lost their hemolytic effects. To increase the stability of the peptide, melittin-dKLA8-26 fragment was conjugated with PEGylation at the amino terminus and was named PEG-melittin-dKLA8-26. This final drug candidate was assessed in vivo in a murine TNBC model and showed superior effects on tumor growth, survival rates, and lung metastasis compared with the previously used melittin-dKLA. Taken together, our study showed that the novel PEG-melittin-dKLA8-26 possesses potential as a new drug for treating TNBC and TNBC-mediated metastasis by targeting TAMs.
Prebiotic Assembly of Cloverleaf tRNA, Its Aminoacylation and the Origin of Coding, Inferred from Acceptor Stem Coding-Triplets
Authors: Agmon Ilana
Published: December 2022

tRNA is a key component in life’s most fundamental process, the translation of the instructions contained in mRNA into proteins. Its role had to be executed as soon as the earliest translation emerged, but the questions of the prebiotic tRNA materialization, aminoacylation, and the origin of the coding triplets it carries are still open. Here, these questions are addressed by utilizing a distinct pattern of coding triplets highly conserved in the acceptor stems from the modern bacterial tRNAs of five early-emerging amino acids. Self-assembly of several copies of a short RNA oligonucleotide that carries a related pattern of coding triplets, via a simple and statistically feasible process, is suggested to result in a proto-tRNA model highly compatible with the cloverleaf secondary structure of the modern tRNA. Furthermore, these stem coding triplets evoke the possibility that they were involved in self-aminoacylation of proto-tRNAs prior to the emergence of the earliest synthetases, a process proposed to underlie the formation of the genetic code. Being capable of autonomous materialization and of self-aminoacylation, this verifiable model of the proto-tRNA advent adds principal components to an initial set of molecules and processes that may have led, exclusively through natural means, to the emergence of life.
Helicobacter pylori-Associated Iron Deficiency Anemia in Childhood and Adolescence-Pathogenesis and Clinical Management Strategy
Authors: Kato Seiichi , Gold Benjamin D. , Kato Ayumu
Published: December 2022

Many epidemiological studies and meta-analyses show that persistent Helicobacter pylori infection in the gastric mucosa can lead to iron deficiency or iron deficiency anemia (IDA), particularly in certain populations of children and adolescents. Moreover, it has been demonstrated that H. pylori infection can lead to and be closely associated with recurrent and/or refractory iron deficiency and IDA. However, the pathogenesis and specific risk factors leading to this clinical outcome in H. pylori-infected children remain poorly understood. In general, most of pediatric patients with H. pylori-associated IDA do not show evidence of overt blood loss due to gastrointestinal hemorrhagic lesions. In adult populations, H. pylori atrophic gastritis is reported to cause impaired iron absorption due to impaired gastric acid secretion, which, subsequently, results in IDA. However, significant gastric atrophy, and the resultant substantial reduction in gastric acid secretion, has not been shown in H. pylori-infected children. Recently, it has been hypothesized that competition between H. pylori and humans for iron availability in the upper gastrointestinal tract could lead to IDA. Many genes, including those encoding major outer membrane proteins (OMPs), are known to be involved in iron-uptake mechanisms in H. pylori. Recent studies have been published that describe H. pylori virulence factors, including specific OMP genes that may be associated with the pathogenesis of IDA. Daily iron demand substantively increases in children as they begin pubertal development starting with the associated growth spurt, and this important physiological mechanism may play a synergistic role for the microorganisms as a host pathogenetic factor of IDA. Like in the most recent pediatric guidelines, a test-and-treat strategy in H. pylori infection should be considered, especially for children and adolescents in whom IDA is recurrent or refractory to iron supplementation and other definitive causes have not been identified. This review will focus on providing the evidence that supports a clear biological plausibility for H. pylori infection and iron deficiency, as well as IDA.
Multi-Level Decision Support System in Production and Safety Management
Authors: Massaro Alessandro
Published: December 2022

The proposed paper introduces an innovative approach based on the implementation of a multi-level Decision Support System (DSS) modelling processes in the industry. Specifically, the work discusses a theoretical Process Mining (PM) DSS model gaining digital knowledge by means of logics that are able to select the best decisions. The PM model is applied to an open dataset simulating a working scenario and defining a possible safety control method based on the risk assessment. The application of the PM model provides automatic alerting conditions based on a threshold of values detected by sensors. Specifically, the PM model is applied to worker security systems characterized by the environment with a risk of emission of smoke and gases. The PM model is improved by Artificial Intelligence (AI) algorithms by strengthening information through prediction results and improving the risk analysis. An Artificial Neural Network (ANN) MultilaLayer Perceptron (MLP) algorithm is adopted for the risk prediction by achieving the good computational performance of Mean Absolute Error (MAE) of 0.001. The PM model is first sketched by the Business Process Modelling and Notation (BPMN) method, and successively executed by means of the Konstanz Information Miner (KNIME) open source tool, implementing the process-controlling risks for different working locations. The goal of the paper is to apply the theoretical PM model by means of open source tools by enhancing how the multi-level approach is useful for defining a security procedure to control indoor worker environments. Furthermore, the article describes the key variables able to control production and worker safety for different industry sectors. The presented DSS PM model also can be applied to industry processes focused on production quality.
Simulation of Far-Field Light Distribution of Micro-LED Based on Its Structural Parameters
Authors: Wei Wei , Chen Yiying , Wang Chenxi , Peng Xing , Tang Tang , Chen Zhizhong
Published: December 2022

To clarify how micro-LED far-field light distributions differ from Lambertian distributions owing to small-sized-structure effects, the light distribution of a micro-LED was simulated via the ray-tracing method in this study. Specifically, considering material absorption, far-field light distribution, and light-output efficiency, we studied micro-LEDs as a function of size. We found that the light distribution is the most uniform and the efficiency is the highest when the size is the smallest under certain conditions. Under other conditions, with increasing sapphire size, the luminous efficiency first increases and then decreases. The luminous efficiency is the highest when the thickness is 30 µm. Under certain other conditions, as the diameter of the micro-sphere structure on the sapphire increases, the luminous efficiency first increases and then decreases.
Marine Polyphenol Phlorotannins as a Natural Sleep Aid for Treatment of Insomnia: A Review of Sedative–Hypnotic Effects and Mechanism of Action
Authors: Kim Seonghui , Kim Duhyeon , Um Min , Yoon Minseok , Choi Jae-Suk , Choi Yung , Cho Suengmok
Published: December 2022

Insomnia is a common sleep disorder. Natural sleep aids are gaining worldwide popularity as alternatives to prescription drugs for improving sleep. Recently, numerous studies have investigated the sedative–hypnotic effects of the polyphenols of terrestrial plants. The hypnotic effects of marine polyphenols have also been studied in recent years. Phlorotannins are marine polyphenols that are found only in brown algae. Phlorotannins exert sedative–hypnotic effects via the gamma-aminobutyric acid type A-benzodiazepine receptor. In addition, the brown seaweed Ecklonia cava supplement containing phlorotannins has been approved by the Ministry of Food and Drug Safety as a health-functional ingredient that helps improve sleep quality. Currently, it is meaningful to deal with the sedative–hypnotic effects of phlorotannins as natural sleep aids. The current review comprehensively presents the sedative–hypnotic effects in animal models and human clinical trials as well as their mechanism of action, extraction, purification, and safety.
Vasorelaxant Mechanism of Herbal Extracts from Mentha suaveolens, Conyza canadensis, Teucrium polium and Salvia verbenaca in the Aorta of Wistar Rats
Authors: El-Akhal Jamila , Oliveira Andreia P. , Bencheikh Rachid , Valentão Patrícia , Andrade Paula B. , Morato Manuela
Published: December 2022

Mentha suaveolens (MS), Conyza canadensis (CC), Teucrium polium (TP) and Salvia verbenaca (SV) are used in Morocco to treat hypertension. Our aim was to characterize the composition and vasoreactivity of extracts of MS, CC, TP and SV. The chemical compositions of aqueous extracts of MS, SV and TP, and of a hydromethanolic extract of CC, were identified by HPLC-DAD. The vasoreactive effect was tested in rings of the thoracic aorta of female Wistar rats (8–14 weeks-old) pre-contracted with 10 µM noradrenaline, in the absence or presence of L-NAME 100 µM, indomethacin 10 µM or atropine 6 µM, to inhibit nitric oxide synthase, cyclooxygenase or muscarinic receptors, respectively. L-NAME and atropine decreased the vasorelaxant effect caused by low concentrations of MS. Atropine and indomethacin decreased the vasorelaxant effect of low concentrations of SV. High concentrations of MS or SV and the effect of SV and TP were not altered by any antagonist. The activation of muscarinic receptors and NO or the cyclooxygenase pathway underlie the vasorelaxant effect of MS and SV, respectively. Neither of those mechanisms underlines the vasorelaxant effect of CC and TP. These vasorelaxant effect might support the use of herbal teas from these plants as anti-hypertensives in folk medicine.
Design, Synthesis and Biological Evaluation of Syn and Anti-like Double Warhead Quinolinones Bearing Dihydroxy Naphthalene Moiety as Epidermal Growth Factor Receptor Inhibitors with Potential Apoptotic Antiproliferative Action
Authors: El-Sheref Essmat M. , Ameen Mohamed A. , El-Shaieb Kamal M. , Abdel-Latif Fathy F. , Abdel-naser Asmaa I. , Brown Alan B. , Bräse Stefan , Fathy Hazem M. , Ahmad Iqrar , Patel Harun , Gomaa Hesham A. M. , Youssif Bahaa G. M. , Mohamed Asmaa H.
Published: December 2022

Our investigation includes the synthesis of new naphthalene-bis-triazole-bis-quinolin-2(1H)-ones 4a–e and 7a–e via Cu-catalyzed [3 + 2] cycloadditions of 4-azidoquinolin-2(1H)-ones 3a–e with 1,5-/or 1,8-bis(prop-2-yn-1-yloxy)naphthalene (2) or (6). All structures of the obtained products have been confirmed with different spectroscopic analyses. Additionally, a mild and versatile method based on copper-catalyzed [3 + 2] cycloaddition (Meldal–Sharpless reaction) was developed to tether quinolinones to O-atoms of 1,5- or 1,8-dinaphthols. The triazolo linkers could be considered as anti and syn products, which are interesting precursors for functionalized epidermal growth factor receptor (EGFR) inhibitors with potential apoptotic antiproliferative action. The antiproliferative activities of the 4a–e and 7a–e were evaluated. Compounds 4a–e and 7a–e demonstrated strong antiproliferative activity against the four tested cancer cell lines, with mean GI50 ranging from 34 nM to 134 nM compared to the reference erlotinib, which had a GI50 of 33 nM. The most potent derivatives as antiproliferative agents, compounds 4a, 4b, and 7d, were investigated for their efficacy as EGFR inhibitors, with IC50 values ranging from 64 nM to 97 nM. Compounds 4a, 4b, and 7d demonstrated potent apoptotic effects via their effects on caspases 3, 8, 9, Cytochrome C, Bax, and Bcl2. Finally, docking studies show the relevance of the free amino group of the quinoline moiety for antiproliferative action via hydrogen bond formation with essential amino acids.
Study on Volumetric, Compressibility and Viscometric Behavior of Cationic Surfactants (CTAB and DTAB) in Aqueous Glycyl Dipeptide: A Thermo-Acoustic Approach
Authors: Kumari Santosh , Chauhan Suvarcha , Singh Kuldeep , Umar Ahmad , Fouad Hassan , Akhtar Mohammad Shaheer
Published: December 2022

This study aims to understand how glycyl dipeptide affected the compressibility, volumetric behavior and viscometric behavior of the cationic surfactants CTAB (Cetyltrimethylammonium bromide) and DTAB (dodecyltrimethylammonium bromide). Information on solute–solute, solute–solvent, and solvent–solvent interactions has been inferred using the quantification of density (ρ), speed of sound (u) and viscosity in aqueous media containing glycyl dipeptide in the temperature range 293.15–313.15 K at an interval of 5 K. The data from the aforementioned research have been used to enumerate numerous volumetric and compressibility metrics that aid in the collection of information about the interactional behavior of the system under consideration. The study suggests that CTAB interacts strongly compared to DTAB with dipeptide, and it also significantly dehydrates glycyl dipeptide. The difference in water–water interactions caused by the loss of hydrophobic hydration of the surfactant molecules upon the addition of cationic surfactants may be the cause of the variation in determined parameters with surfactant concentration. Consideration of the structural rearrangement of molecules that may occur in the system has been used to explain the results of viscosity and computed factors related to viscosity. The patterns of competitive intermolecular interactions in the ternary (dipeptide + water + surfactant) system have been used to analyze the trends of all the parameters. The study may be helpful to understand the stability and structural changes in protein–surfactant systems mediated through various interactions that may be present in the system.