bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical Study of Doping in GaOOH for Electronics Applications
Authors: Ichimura Masaya
Published: November 2023

GaOOH, having a bandgap of 4.7–4.9 eV, can be regarded as one of several ultrawide-bandgap (UWBG) semiconductors, although it has so far mainly been used as a precursor material of Ga2O3. To examine the possibility of valence control and application in electronics, impurity levels in GaOOH are investigated using the first-principles density-functional theory calculation. The density values of the states of a supercell including an impurity atom are calculated. According to the results, among the group 14 elements, Si is expected to introduce a shallow donor level, i.e., a free electron is introduced. On the other hand, Ge and Sn introduce a localized state about 0.7 eV below the conduction band edge, and thus cannot act as an effective donor. While Mg and Ca can introduce a free hole and act as a shallow acceptor, Zn and Cd introduce acceptor levels away from the valence band. The transition metal elements (Fe, Co, Ni, Cu) are also considered, but none of them are expected to act as a shallow dopant. Thus, the results suggest that the carrier concentration can be controlled if Si is used for n-type doping, and Mg and Ca for p-type doping. Since GaOOH can be easily deposited using various chemical techniques at low temperatures, GaOOH will potentially be useful for transparent electronic devices.
Shock Tube Study of Ignition Delay Times for Hydrogen–Oxygen Mixtures
Authors: Pavlov Valery , Gerasimov Gennady , Levashov Vladimir , Kozlov Pavel , Zabelinsky Igor , Bykova Natalia
Published: November 2023

This paper presents the results of measurements of ignition delay times in hydrogen–oxygen mixtures highly diluted with argon. The experiments were carried out behind an incident shock wave at temperatures from 870 to 2500 K, pressures from 0.5 to 1.5 atm, and equivalence ratios from 0.1 to 2.0. The results obtained were processed in terms of the partial pressure of the combustible mixture stoichiometric part that is consumed in the combustion process. An almost linear dependence of the ignition delay time on the reciprocal value of the partial pressure was found for both rich and lean mixtures. The measured data are compared with calculations based on the previously developed kinetic model and experimental data from other authors.
Study on the Influence of Ventilation Speed on Smoke and Temperature Characteristics of Complex Underground Spaces
Authors: Ou Jianchun , Wang Xinyu , Ming Yuyang , Sun Xixi
Published: November 2023

This study explores the intricate behaviors of smoke flow, temperature distribution, carbon monoxide (CO) levels, and visibility dynamics within complex underground spaces during fire incidents. A key revelation is the profound impact of ventilation speed, with the identification of a critical range between 2 and 3 m/s that consistently proves to be instrumental in curbing smoke-related hazards and ensuring the safe evacuation of personnel. Furthermore, this paper underscores the influence of accelerated longitudinal winds on temperature profiles, particularly under high HRR conditions, underscoring the importance of accounting for wind effects in comprehensive fire response strategies. Regarding CO concentration, which is a critical safety concern, this study demonstrates that higher ventilation speeds effectively reduce hazardous gas levels, thereby fortifying overall safety measures. The visibility is analyzed, with the findings indicating that elevated ventilation speeds enhance visibility, albeit with considerations about potential drawbacks on personnel evacuation due to excessive wind speed. In conclusion, this paper offers a comprehensive understanding of the pivotal role played by ventilation speed in underground space safety by encompassing smoke control and temperature management.
Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats
Authors: Marañón Rodrigo Oscar , Moulana Mohadetheh
Published: November 2023

In recent decades, the roles of tacrolimus and mycophenolate mofetil (MMF) in hypertension have been under discussion. However, the question of whether there are sex-specific responses to these agents has not received enough attention. Aim: To evaluate sex-specific differences in the responses to tacrolimus and mycophenolate mofetil in female (F) and male (M) spontaneously hypertensive rats (SHRs) and evaluate whether T cells contribute to mean arterial pressure (MAP) changes. Methods: Male and female SHRs received either tacrolimus or MMF for 14 days. The rats were implanted with radiotelemeters. MAP was measured chronically; then, circulating and renal infiltrated CD4+, CD8+, T helper 17 (Th17), and T regulatory (Treg) cells were quantified using flow cytometry. Key Findings: Tacrolimus increased MAP only in males, and it decreased CD4+ and CD8+ T cells in both males and females (p < 0.05). The tacrolimus-induced reduction of renal CD4+ and Treg cells was more profound in males. MMF reduced MAP and circulating and renal CD4+ and CD8+ T cells in the male and female rats. MMF also decreased Th17 and Treg cells in both sexes, but the decrease in Th17 was higher in males (p < 0.05) and the reduction in Treg cells was higher in females (p < 0.05). Our findings indicate that the effects of tacrolimus and MMF on renal T cell subsets are sex-specific. Significance: Targeting T cells in hypertension using therapeutic agents may have different effects on men and women; so, the management of hypertension and post-transplant hypertension using these agents should be specified by gender.
How Tolerant Are Hydroids to Climate-Change-Induced Acute Spikes in Sea Water Temperature? A Case Study of Arctic Dynamena pumila (L., 1758)
Authors: Marfenin Nikolay N. , Dementyev Vitaly S. , Nikolaev Evgeny V.
Published: November 2023

The temperature of the water surface layer in the Arctic may increase significantly in the coming decades. To what extent will shallow-water fauna be affected by warming? We investigated this issue using an example of one species of colonial hydroid, Dynamena pumila. We judged its reaction to warming via its pulsation activity and the growth of stolons. Pulsations of the coenosarc in colonial hydroids are a sensitive indicator of the body’s reaction to the influence of environmental factors. We tested the ability of D. pumila colonies to survive and adapt to existing at 25 °C for five days. After raising the temperature from 14 °C to 25 °C, colony growth and the pulsation of stolon growth tips on the first day increased and then decreased during the day. In the following days, the growth pulsations almost ceased, the colonies stopped growing, and their coenosarcs began to exfoliate from their perisarcs. However, by the fourth day, this process slowed down, and the colonies existed in an economy mode of experiencing unfavourable conditions. The thermal shock continued in the experiment for five days. Then, after the temperature dropped from 25 °C to 15–16 °C, all the colonies recovered within five days and continued to grow.
Exploring the mRNA and Plasma Protein Levels of BDNF, NT4, SIRT1, HSP27, and HSP70 in Multiple Sclerosis Patients and Healthy Controls
Authors: Sokolowski Igor , Kucharska-Lusina Aleksandra , Miller Elzbieta , Majsterek Ireneusz
Published: November 2023

Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease affecting the central nervous system. It is a major cause of non-traumatic neurological disability among young adults in North America and Europe. This study focuses on neuroprotective genes (BDNF, NT4/5, SIRT1, HSP70, and HSP27). Gene expression and protein levels of these markers were compared between MS patients and healthy controls. Blood samples were collected from 42 patients with multiple sclerosis (MS) and 48 control subjects without MS. Quantitative real-time PCR was performed to measure the expression of specific genes. The samples were analyzed in duplicate, and the abundance of mRNA was quantified using the 2-ΔCt method. ELISA assay was used to measure the concentration of specific proteins in the plasma samples. The results show that a 3.5-fold decrease in the gene expression of BDNF corresponds to a 1.5-fold downregulation in the associated plasma protein concentration (p < 0.001). Similar trends were observed with NT-4 (five-fold decrease, slight elevation in protein), SIRT1 (two-fold decrease, two-fold protein decrease), HSP70 (four-fold increase, nearly two-fold protein increase), and HSP27 (four-fold increase, two-fold protein increase) (p < 0.001). This study reveals strong correlations between gene expression and protein concentration in MS patients, emphasizing the relevance of these neuroprotective markers in the disease.
Dual RNA-Seq Analysis Pinpoints a Balanced Regulation between Symbiosis and Immunity in Medicago truncatula-Sinorhizobium meliloti Symbiotic Nodules
Authors: Zhang Dandan , Wu Qiujin , Zhao Yanwen , Yan Ziang , Xiao Aifang , Yu Haixiang , Cao Yangrong
Published: November 2023

Legume–rhizobial symbiosis initiates the formation of root nodules, within which rhizobia reside and differentiate into bacteroids to convert nitrogen into ammonium, facilitating plant growth. This process raises a fundamental question: how is plant immunity modulated within nodules when exposed to a substantial number of foreign bacteria? In Medicago truncatula, a mutation in the NAD1 (Nodules with Activated Defense 1) gene exclusively results in the formation of necrotic nodules combined with activated immunity, underscoring the critical role of NAD1 in suppressing immunity within nodules. In this study, we employed a dual RNA-seq transcriptomic technology to comprehensively analyze gene expression from both hosts and symbionts in the nad1-1 mutant nodules at different developmental stages (6 dpi and 10 dpi). We identified 89 differentially expressed genes (DEGs) related to symbiotic nitrogen fixation and 89 DEGs from M. truncatula associated with immunity in the nad1-1 nodules. Concurrently, we identified 27 rhizobial DEGs in the fix and nif genes of Sinorhizobium meliloti. Furthermore, we identified 56 DEGs from S. meliloti that are related to stress responses to ROS and NO. Our analyses of nitrogen fixation-defective plant nad1-1 mutants with overactivated defenses suggest that the host employs plant immunity to regulate the substantial bacterial colonization in nodules. These findings shed light on the role of NAD1 in inhibiting the plant’s immune response to maintain numerous rhizobial endosymbiosis in nodules.
Discovery and Visualization of the Hidden Relationships among N-Glycosylation, Disulfide Bonds, and Membrane Topology
Authors: Desai Manthan , Singh Amritpal , Pham David , Chowdhury Syed Rafid , Sun Bingyun
Published: November 2023

Membrane proteins (MPs) are functionally important but structurally complex. In particular, MPs often carry three structural features, i.e., transmembrane domains (TMs), disulfide bonds (SSs), and N-glycosylation (N-GLYCO). All three features have been intensively studied; however, how the three features potentially correlate has been less addressed in the literature. With the growing accuracy from computational prediction, we used publicly available information on SSs and N-GLYCO and analyzed the potential relationships among post-translational modifications (PTMs) and the predicted membrane topology in the human proteome. Our results suggested a very close relationship between SSs and N-GLYCO that behaved similarly, whereas a complementary relation between the TMs and the two PTMs was also revealed, in which the high SS and/or N-GLYCO presence is often accompanied by a low TM occurrence in a protein. Furthermore, the occurrence of SSs and N-GLYCO in a protein heavily relies on the protein length; however, TMs seem not to possess such length dependence. Finally, SSs exhibits larger potential dynamics than N-GLYCO, which is confined by the presence of sequons. The special classes of proteins possessing extreme or unique patterns of the three structural features are comprehensively identified, and their structural features and potential dynamics help to identify their susceptibility to different physiological and pathophysiological insults, which could help drug development and protein engineering.
Expanded Substrate Specificity in D-Amino Acid Transaminases: A Case Study of Transaminase from Blastococcus saxobsidens
Authors: Shilova Sofia A. , Matyuta Ilya O. , Petrova Elizaveta S. , Nikolaeva Alena Y. , Rakitina Tatiana V. , Minyaev Mikhail E. , Boyko Konstantin M. , Popov Vladimir O. , Bezsudnova Ekaterina Yu.
Published: November 2023

Enzymes with expanded substrate specificity are good starting points for the design of biocatalysts for target reactions. However, the structural basis of the expanded substrate specificity is still elusive, especially in the superfamily of pyridoxal-5′-phosphate-dependent transaminases, which are characterized by a conserved organization of both the active site and functional dimer. Here, we analyze the structure–function relationships in a non-canonical D-amino acid transaminase from Blastococcus saxobsidens, which is active towards D-amino acids and primary (R)-amines. A detailed study of the enzyme includes a kinetic analysis of its substrate scope and a structural analysis of the holoenzyme and its complex with phenylhydrazine—a reversible inhibitor and analogue of (R)-1-phenylethylamine—a benchmark substrate of (R)-selective amine transaminases. We suggest that the features of the active site of transaminase from B. saxobsidens, such as the flexibility of the R34 and R96 residues, the lack of bulky residues in the β-turn at the entrance to the active site, and the short O-pocket loop, facilitate the binding of substrates with and without α-carboxylate groups. The proposed structural determinants of the expanded substrate specificity can be used for the design of transaminases for the stereoselective amination of keto compounds.
Quassinoids from Twigs of Harrisonia perforata (Blanco) Merr and Their Anti-Parkinson’s Disease Effect
Authors: Cai Min , Bai Xiao-Lin , Zang Hao-Jing , Tang Xiao-Han , Yan Ying , Wan Jia-Jia , Peng Min-You , Liang Hong , Liu Lin , Guo Feng , Zhao Pei-Ji , Liao Xun , Di Ying-Tong , Hao Xiao-Jiang
Published: November 2023

Six new C-20 and one new C-19 quassinoids, named perforalactones F-L (1–7), were isolated from twigs of Harrisonia perforata. Spectroscopic and X-ray crystallographic experiments were conducted to identify their structures. Through oxidative degradation of perforalactone B to perforaqussin A, the biogenetic process from C-25 quassinoid to C-20 via Baeyer–Villiger oxidation was proposed. Furthermore, the study evaluated the anti-Parkinson’s disease potential of these C-20 quassinoids for the first time on 6-OHDA-induced PC12 cells and a Drosophila Parkinson’s disease model of PINK1B9. Perforalactones G and I (2 and 4) showed a 10–15% increase in cell viability of the model cells at 50 μM, while compounds 2 and 4 (100 μM) significantly improved the climbing ability of PINK1B9 flies and increased the dopamine level in the brains and ATP content in the thoraces of the flies.
Facile Fabrication of Energetic Nanocomposite Materials by Polydopamine
Authors: Song Zhanxin , Liu Wei , Xian Mo , Jin Miaomiao
Published: November 2023

Polydopamine-based materials have been widely investigated for incorporation in energetic nanocomposites due to their outstanding adherence. However, these materials are often prepared in alkaline environments, which negatively affects Al nanoparticles. In this study, a one-pot assembly was devised for the preparation of a polydopamine-based Al/CuO energetic nanocomposite material (Al/PDA/CuO) in a neutral environment. The CuO and Al nanoparticles of the Al/PDA/CuO nanothermite were uniformly dispersed and closely combined. Consequently, the Al/PDA/CuO nanothermite was able to release more heat (2069.7 J/g) than physically mixed Al/CuO (1438.9 J/g). Furthermore, the universality of using polydopamine in the assembly of different types of energetic nanocomposite materials was verified, including an organic energetic material-nanothermit (HMX/PDA/Al/CuO nanothermite) and an inorganic oxidant-metal nanocatalyst (AP/PDA/Fe2O3). This study provides a promising route for the preparation of polydopamine-based energetic nanocomposites in neutral aqueous solutions.
The Unfolded Protein Response in a Murine Model of Alzheimer’s Disease: Looking for Predictors
Authors: Sita Giulia , Graziosi Agnese , Corrieri Camilla , Ghelli Luca , Angelini Sabrina , Cortelli Pietro , Hrelia Patrizia , Morroni Fabiana
Published: November 2023

Alzheimer’s disease (AD) represents the most frequent type of dementia worldwide, and aging is the most important risk factor for the sporadic form of the pathology. The endoplasmic reticulum (ER), the main cellular actor involved in proteostasis, appears significantly compromised in AD due to the accumulation of the β-amyloid (Aβ) protein and the phosphorylated Tau protein. Increasing protein misfolding activates a specific cellular response known as Unfolded Protein Response (UPR), which orchestrates the recovery of ER function. The aim of the present study was to investigate the role of UPR in a murine model of AD induced by intracerebroventricular (i.c.v.) injection of Aβ1–42 oligomers at 3 or 18 months. The oligomer injection in aged animals induced memory impairment, oxidative stress, and the depletion of glutathione reserve. Furthermore, the RNA sequencing and the bioinformatic analysis performed showed the enrichment of several pathways involved in neurodegeneration and protein regulations. The analysis highlighted the significant dysregulation of the protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α) and activating transcription factor 6 (ATF-6). In turn, ER stress affected the PI3K/Akt/Gsk3β and MAPK/ERK pathways, highlighting Mapkapk5 as a potential marker, whose regulation could lead to the definition of new pharmacological and neuroprotective strategies to counteract AD.
Flow Cytometry and Its Applications to Molecular Biology and Diagnosis 2.0
Authors: Papa Stefano , Ortolani Claudio , Fernández Paula , O’Connor José-Enrique
Published: November 2023

Flow cytometry is a single-cell based technology aimed to quantify the scattering of light and the emission of multiple fluorescence signals by individual cells, biological vesicles, or synthetic microscopical particles when examined one by one at high speed using lasers or other suitable illumination sources [...]
The Interplay of Permeability, Metabolism, Transporters, and Dosing in Determining the Dynamics of the Tissue/Plasma Partition Coefficient and Volume of Distribution—A Theoretical Investigation Using Permeability-Limited, Physiologically Based Pharmacokinetic Modeling
Authors: Gaohua Lu , Zhang Mian , Sychterz Caroline , Chang Ming , Schmidt Brian James
Published: November 2023

A permeability-limited physiologically based pharmacokinetic (PBPK) model featuring four subcompartments (corresponding to the intracellular and extracellular water of the tissue, the residual plasma, and blood cells) for each tissue has been developed in MATLAB/SimBiology and applied to various what-if scenario simulations. This model allowed us to explore the complex interplay of passive permeability, metabolism in tissue or residual blood, active uptake or efflux transporters, and different dosing routes (intravenous (IV) or oral (PO)) in determining the dynamics of the tissue/plasma partition coefficient (Kp) and volume of distribution (Vd) within a realistic pseudo-steady state. Based on the modeling exercise, the permeability, metabolism, and transporters demonstrated significant effects on the dynamics of the Kp and Vd for IV bolus administration and PO fast absorption, but these effects were not as pronounced for IV infusion or PO slow absorption. Especially for low-permeability compounds, uptake transporters were found to increase both the Kp and Vd at the pseudo-steady state (Vdss), while efflux transporters had the opposite effect of decreasing the Kp and Vdss. For IV bolus administration and PO fast absorption, increasing tissue metabolism was predicted to elevate the Kp and Vdss, which contrasted with the traditional derivation from the steady-state perfusion-limited PBPK model. Moreover, metabolism in the residual blood had more impact on the Kp and Vdss compared to metabolism in tissue. Due to its ability to offer a more realistic description of tissue dynamics, the permeability-limited PBPK model is expected to gain broader acceptance in describing clinical PK and observed Kp and Vdss, even for certain small molecules like cyclosporine, which are currently treated as perfusion-limited in commercial PBPK platforms.
Conformational States of the CXCR4 Inhibitor Peptide EPI-X4—A Theoretical Analysis
Authors: Jung Christoph Karsten , Münch Jan , Jacob Timo
Published: November 2023

EPI-X4, an endogenous peptide inhibitor, has exhibited potential as a blocker of CXCR4—a G protein-coupled receptor. This unique inhibitor demonstrates the ability to impede HIV-1 infection and halt CXCR4-dependent processes such as tumor cell migration and invagination. Despite its promising effects, a comprehensive understanding of the interaction between EPI-X4 and CXCR4 under natural conditions remains elusive due to experimental limitations. To bridge this knowledge gap, a simulation approach was undertaken. Approximately 150,000 secondary structures of EPI-X4 were subjected to simulations to identify thermodynamically stable candidates. This simulation process harnessed a self-developed reactive force field operating within the ReaxFF framework. The application of the Two-Phase Thermodynamic methodology to ReaxFF facilitated the derivation of crucial thermodynamic attributes of the EPI-X4 conformers. To deepen insights, an ab initio density functional theory calculation method was employed to assess the electrostatic potentials of the most relevant (i.e., stable) EPI-X4 structures. This analytical endeavor aimed to enhance comprehension of the inhibitor’s structural characteristics. As a result of these investigations, predictions were made regarding how EPI-X4 interacts with CXCR4. Two pivotal requirements emerged. Firstly, the spatial conformation of EPI-X4 must align effectively with the CXCR4 receptor protein. Secondly, the functional groups present on the surface of the inhibitor’s structure must complement the corresponding features of CXCR4 to induce attraction between the two entities. These predictive outcomes were based on a meticulous analysis of the conformers, conducted in a gaseous environment. Ultimately, this rigorous exploration yielded a suitable EPI-X4 structure that fulfills the spatial and functional prerequisites for interacting with CXCR4, thus potentially shedding light on new avenues for therapeutic development.
Transcriptome Shock in Developing Embryos of a Brassica napus and Brassica rapa Hybrid
Authors: Zhou Weixian , Zhang Libin , He Jianjie , Chen Wang , Zhao Feifan , Fu Chunhua , Li Maoteng
Published: November 2023

Interspecific crosses that fuse the genomes of two different species may result in overall gene expression changes in the hybrid progeny, called ‘transcriptome shock’. To better understand the expression pattern after genome merging during the early stages of allopolyploid formation, we performed RNA sequencing analysis on developing embryos of Brassica rapa, B. napus, and their synthesized allotriploid hybrids. Here, we show that the transcriptome shock occurs in the developing seeds of the hybrids. Of the homoeologous gene pairs, 17.1% exhibit expression bias, with an overall expression bias toward B. rapa. The expression level dominance also biases toward B. rapa, mainly induced by the expression change in homoeologous genes from B. napus. Functional enrichment analysis revealed significant differences in differentially expressed genes (DEGs) related to photosynthesis, hormone synthesis, and other pathways. Further study showed that significant changes in the expression levels of the key transcription factors (TFs) could regulate the overall interaction network in the developing embryo, which might be an essential cause of phenotype change. In conclusion, the present results have revealed the global changes in gene expression patterns in developing seeds of the hybrid between B. rapa and B. napus, and provided novel insights into the occurrence of transcriptome shock for harnessing heterosis.
Characterization of a miRNA Signature with Enhanced Diagnostic and Prognostic Power for Patients with Bladder Carcinoma
Authors: Samara Maria , Vlachostergios Panagiotis J. , Thodou Eleni , Zachos Ioannis , Mitrakas Lampros , Evmorfopoulos Konstantinos , Tzortzis Vassilios , Giakountis Antonis
Published: November 2023

Bladder carcinoma is globally among the most prevalent cancers and is associated with a high mortality rate at advanced stages. Its detection relies on invasive diagnostic methods that are unpleasant for the patient. Non-invasive molecular biomarkers, such as miRNAs, could serve as alternatives for early detection and prognosis of this malignancy. We designed a computational approach that combines transcriptome profiling, survival analyses, and calculation of diagnostic power in order to isolate miRNA signatures with high diagnostic and prognostic utility. Our analysis of TCGA-BLCA data from 429 patients yielded one miRNA signature, consisting of five upregulated and three downregulated miRNAs with cumulative diagnostic power that outperforms current diagnostic methods. The same miRNAs have a strong prognostic significance since their expression is associated with the overall survival of bladder cancer patients. We evaluated the expression of this signature in 19 solid cancer types, supporting its unique diagnostic utility for bladder carcinoma. We provide computational evidence regarding the functional implications of this miRNA signature in cell cycle regulation, demonstrating its abundance in body fluids, including peripheral blood and urine. Our study characterized a novel miRNA signature with the potential to serve as a non-invasive method for bladder cancer diagnosis and prognosis.
Evaluation of Biological Equivalence for Generic Tulathromycin Injections in Cattle
Authors: Kang JeongWoo , Chae HyunYoung , Jeong SungHoon , Pervin Rokeya , Hossain Md Akil
Published: November 2023

The recent expiration of patents for the antibiotic tulathromycin has led to a significant increase in the number of generic tulathromycin products (GTPs) available. This study aims to evaluate the bioequivalence of four GTPs, which experienced a rapid increase in market share. The bioequivalence was evaluated by performing pharmacokinetic assessments. The four selected GTPs (Tulaject, Tulagen, Toulashot, and T-raxxin) were compared with the reference product, Draxxin. A dose of 2.5 mg/kg.bw/day was administered via subcutaneous injection, and blood samples were collected 460 times from 20 Holstein cattle. Plasma concentrations of tulathromycin were measured over time using LC-MS/MS analysis. Bioequivalence was evaluated using a statistical program for pharmacokinetic parameters, including the area under the concentration time curve (AUC) and the maximum plasma concentration (Cmax). The bioequivalence was considered proven if the difference between the test and reference products was within 20% for both AUC and Cmax. The results showed that the confidence interval (CI, 90%) for both AUC and Cmax values was within the 80~120% range, demonstrating the bioequivalence of the four GTPs compared to Draxxin. This study provides evidence for the bioequivalence of the selected GTPs, contributing to their validation for use as effective antibiotics.
Mesenchymal Stromal Cells Primed by Toll-like Receptors 3 and 4 Enhanced Anti-Inflammatory Effects against LPS-Induced Macrophages via Extracellular Vesicles
Authors: Hwang Sein , Sung Dong Kyung , Kim Young Eun , Yang Misun , Ahn So Yoon , Sung Se In , Chang Yun Sil
Published: November 2023

Although it has been suggested that toll-like receptor (TLR) 3 and TLR4 activation alters mesenchymal stromal cells (MSCs)’ immunoregulatory function as anti- or pro-inflammatory phenotypes, we have previously confirmed that TLR4-primed hUCB-MSCs alleviate lung inflammation and tissue injury in an E. coli-induced acute lung injury (ALI) mouse model. Therefore, we hypothesized that strong stimulation of TLR3 or TLR4 prompts hUCB-MSCs to exhibit an anti-inflammatory phenotype mediated by extracellular vesicles (EVs). In this study, we compared the anti-inflammatory effect of TLR3-primed and TLR4-primed hUCB-MSCs against an LPS-induced ALI in vitro model by treating MSCs, MSC-derived conditioned medium (CM), and MSC-derived extracellular vesicles (EVs). LPS-induced rat primary alveolar macrophage and RAW 264.7 cells were treated with naïve, TLR3-, and TLR4-primed MSCs and their derived CM and EVs. Flow cytometry and ELISA were used to evaluate M1-M2 polarization of macrophages and pro-inflammatory cytokine levels, respectively. LPS-stimulated macrophages showed significantly increased pro-inflammatory cytokines compared to those of the normal control, and the percentage of M2 macrophage phenotype was predominantly low. In reducing the inflammatory cytokines and enhancing M2 polarization, TLR3- and TLR4-primed MSCs were significantly more effective than the naïve MSCs, and this finding was also observed with the treatment of MSC-derived CMs and EVs. No significant difference between the efficacy of TLR3- and TLR-primed MSCs was observed. Strong stimulation of TLR3- and TLR4-stimulated hUCB-MSCs significantly reduced pro-inflammatory cytokine secretion from LPS-induced macrophages and significantly enhanced the M2 polarization of macrophages. We further confirmed that TLR-primed MSC-derived EVs can exert anti-inflammatory and immunosuppressive effects alone comparable to MSC treatment. We hereby suggest that in the LPS-induced macrophage in vitro model, EVs derived from both TLR3 and TLR4-primed MSCs can be a therapeutic candidate by promoting the M2 phenotype.
Genome Assembly of Cordia subcordata, a Coastal Protection Species in Tropical Coral Islands
Authors: Chen Yi-Lan , Wang Zheng-Feng , Jian Shu-Guang , Liao Hai-Min , Liu Dong-Ming
Published: November 2023

Cordia subcordata trees or shrubs, belonging to the Boraginaceae family, have strong resistance and have adapted to their habitat on a tropical coral island in China, but the lack of genome information regarding its genetic background is unclear. In this study, the genome was assembled using both short/long whole genome sequencing reads and Hi–C reads. The assembled genome was 475.3 Mb, with 468.7 Mb (99.22%) of the sequences assembled into 16 chromosomes. Repeat sequences accounted for 54.41% of the assembled genome. A total of 26,615 genes were predicted, and 25,730 genes were functionally annotated using different annotation databases. Based on its genome and the other 17 species, phylogenetic analysis using 336 single-copy genes obtained from ortholog analysis showed that C. subcordata was a sister to Coffea eugenioides, and the divergence time was estimated to be 77 MYA between the two species. Gene family evolution analysis indicated that the significantly expanded gene families were functionally related to chemical defenses against diseases. These results can provide a reference to a deeper understanding of the genetic background of C. subcordata and can be helpful in exploring its adaptation mechanism on tropical coral islands in the future.
A Compact Particle Detector for Space-Based Applications: Development of a Low-Energy Module (LEM) for the NUSES Space Mission
Authors: Nicolaidis Riccardo , Nozzoli Francesco , Pepponi Giancarlo ,   on behalf of the NUSES Collaboration
Published: November 2023

NUSES is a planned space mission aiming to test new observational and technological approaches related to the study of relatively low-energy cosmic rays, gamma rays, and high-energy astrophysical neutrinos. Two scientific payloads will be hosted onboard the NUSES space mission: Terzina and Zirè. Terzina will be an optical telescope readout by SiPM arrays, for the detection and study of Cerenkov light emitted by Extensive Air Showers generated by high-energy cosmic rays and neutrinos in the atmosphere. Zirè will focus on the detection of protons and electrons up to a few hundred MeV and to 0.1–10 MeV photons and will include the Low Energy Module (LEM). The LEM will be a particle spectrometer devoted to the observation of fluxes of relatively low-energy electrons in the 0.1–7-MeV range and protons in the 3–50 MeV range along the Low Earth Orbit (LEO) followed by the hosting platform. The detection of Particle Bursts (PBs) in this Physics channel of interest could give new insight into the understanding of complex phenomena such as eventual correlations between seismic events or volcanic activity with the collective motion of particles in the plasma populating van Allen belts. With its compact sizes and limited acceptance, the LEM will allow the exploration of hostile environments such as the South Atlantic Anomaly (SAA) and the inner Van Allen Belt, in which the anticipated electron fluxes are on the order of 106 to 107 electrons per square centimeter per steradian per second. Concerning the vast literature of space-based particle spectrometers, the innovative aspect of the LEM resides in its compactness, within 10 × 10 × 10 cm3, and in its “active collimation” approach dealing with the problem of multiple scattering at these very relatively low energies. In this work, the geometry of the detector, its detection concept, its operation modes, and the hardware adopted will be presented. Some preliminary results from the Monte Carlo simulation (Geant4) will be shown.
Thermal Characteristics Enhancement of AN/Mg/NC Composite Using Activated Carbon/Cobalt Oxide as Highly Effective Catalytic Additive
Authors: Yelemessova Zhanerke , Kydyrbekova Symbat , Yerken Ayan
Published: November 2023

Our study examined the potential of using activated carbon/nanosized cobalt oxide (AC-Co3O4) as a new catalytic additive to improve the efficiency of the parent ammonium nitrate/magnesium/nitrocellulose (AN/Mg/NC) composite. These findings demonstrate a significant improvement in the thermal characteristics of AN/Mg/NC/AC-Co3O4 compared to the initial AN/Mg/NC. Raman spectra confirmed the multilayered nature of AC. Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the presence of cobalt oxide in the synthesized additive. Differential scanning calorimetry (DSC) revealed the catalytic effect of AC-Co3O4 on the AN/Mg/NC composite, resulting in the reduction in the decomposition peak temperature (Tmax) from 277.4 °C (for AN/Mg/NC) to 215.2 °C (for AN/Mg/NC/AC-Co3O4). Thermal gravimetric analysis (TG) determined the overall mass losses (%) for AN/Mg/NC (70%), AN/Mg/NC/AC (75%), and AN/Mg/NC/AC-Co3O4 (80%). This analysis highlights the significant role of AC-Co3O4 in enhancing the energy release during decomposition. Moreover, the use of the differential thermogravimetric (DTG) technique demonstrated the two-step decomposition pathways attributed to the multi-component system. Finally, the combustion tests under the pressure of 3.5 MPa validated the catalytic efficiency of the AC-Co3O4 additive, which enhanced the burning rate (rb) of the AN/Mg/NC/AC-Co3O4 composite from 10.29 to 19.84 mm/s compared to the initial AN/Mg/NC composite. The advantageous nature of the AN/Mg/NC/AC-Co3O4 composite with a lowered decomposition temperature can be applied in rocket propulsion systems, where the precise control of combustion and ignition processes is crucial.
Vocal Cues to Assess Arousal State of Bottlenose Dolphins (Tursiops spp.) Involved in Public Presentations
Authors: Probert Rachel , James Bridget S. , Elwen Simon H. , Gridley Tess
Published: November 2023

Emotions in animals may be expressed by arousal and understanding this often relies upon the monitoring of their behaviour. Under human care, animals’ arousal states may be linked to husbandry decisions, whereby animals may display arousal responses to scheduled events such as feeding and human interaction. Here, we investigate vocal correlates of arousal associated with public presentations of bottlenose dolphins (Tursiops spp.) in human care by comparing vocal production rates and characteristics between high and low arousal contexts. Elevated arousal during the day compared with overnight was characterised by increased signature and non-signature whistle production. High intensity broadband crack vocalisations were produced less than whistles during the day and did not correlate with increased arousal around presentation times. Three of ten dolphins increased signature whistle production before and/or after presentation sessions, indicating elevated arousal and variation in individual responses. Many individuals elevated minimum frequency and suppressed maximum frequency of signature whistles in a way that correlated with higher arousal contexts, indicating that these may therefore be good indicators of changes in arousal state. Overall, our study demonstrates that passive acoustic monitoring can provide a useful indication of arousal linked to husbandry decisions, and that individual variation in vocal responses, likely linked to personality, is important to consider.
The Computed Sinusoid
Authors: Boninsegna Matteo , McCourt Peter A. G. , Holte Christopher Florian
Published: November 2023

Hepatic sinusoids are lined with thin endothelial cells with transcellular pores, termed fenestrations. These fenestrations are open channels that connect the sinusoidal lumen to the underlying Space of Disse (SoD) and the hepatocytes of the liver parenchyma. Fenestrations range from 0.05 to 0.35 µm in diameter and cover 5–15% of the sinusoidal endothelial surface area, depending on their location along the sinusoids. The direct measurement of hemodynamic parameters, such as pressure and flow velocity, remains challenging within the narrow sinusoids. Such knowledge would increase our understanding of the physiology of the hepatic niche and possible implications in aging or diseases in which fenestrations are reduced or lost. Few simulations of liver blood flow focus on the level of the individual sinusoid, and fewer still include the transcellular pores (fenestrations) of the sinusoidal endothelium. Furthermore, none have included (i) a porosity gradient along the sinusoid wall, modeled using through-all pores rather than a porous medium, (ii) the presence of the SoD, or (iii) lymphatic drainage. Herein, computed fluid dynamics (CFD) simulations were performed using a numerical model with relevant anatomical characteristics (length, diameter, porosity, inlet/outlet pressure, and lymphatic outflow from the portal region of the SoD). The greatest contribution to luminal velocity magnitude and pressure was the overall shape of the vessel. Divergent-radius models yielded velocity magnitudes 1.5–2 times higher than constant-radius models, and pressures were 5–8% lower in the divergent-radius models compared to the constant-radius models. Porosity only modestly contributed to luminal pressure. The luminal velocity magnitude was largely unaffected by the presence or absence of lymphatic drainage. Velocity magnitudes through fenestrations were lower in higher-porosity models (20%) vs. lower-porosity models (5%) across all models (0.4–0.55-fold lower). Velocity magnitudes through the space of Disse were increased 3–4 times via the addition of lymphatic drainage to the models, while pressures were decreased by 6–12%. The flow velocity in the SoD was modified via differences in porosity, while the flow velocity in the lumens of the sinusoids was largely unaffected. The overall shape of the vessel is the single most important factor in the pressure flow behavior of the sinusoidal lumen. The flow rate over hepatocytes and the SoD is modestly affected by the distribution of porosity along the sinusoid and greatly affected by the lymphatic drainage, parameters that would be of interest for modeling the exchange of blood with the hepatic parenchyma.
Deep Brain Stimulation for the Management of Refractory Neurological Disorders: A Comprehensive Review
Authors: Rissardo Jamir Pitton , Vora Nilofar Murtaza , Tariq Irra , Mujtaba Amna , Caprara Ana Letícia Fornari
Published: November 2023

In recent decades, deep brain stimulation (DBS) has been extensively studied due to its reversibility and significantly fewer side effects. DBS is mainly a symptomatic therapy, but the stimulation of subcortical areas by DBS is believed to affect the cytoarchitecture of the brain, leading to adaptability and neurogenesis. The neurological disorders most commonly studied with DBS were Parkinson’s disease, essential tremor, obsessive-compulsive disorder, and major depressive disorder. The most precise approach to evaluating the location of the leads still relies on the stimulus-induced side effects reported by the patients. Moreover, the adequate voltage and DBS current field could correlate with the patient’s symptoms. Implantable pulse generators are the main parts of the DBS, and their main characteristics, such as rechargeable capability, magnetic resonance imaging (MRI) safety, and device size, should always be discussed with patients. The safety of MRI will depend on several parameters: the part of the body where the device is implanted, the part of the body scanned, and the MRI-tesla magnetic field. It is worth mentioning that drug-resistant individuals may have different pathophysiological explanations for their resistance to medications, which could affect the efficacy of DBS therapy. Therefore, this could explain the significant difference in the outcomes of studies with DBS in individuals with drug-resistant neurological conditions.
Evaluating the Effectiveness of Magnetic-Pulse Treatment for Healing Continuity Defects in the Metal of Oil and Gas Pipelines
Authors: Schipachev Andrey , Aljadly Mohammed , Ganzulenko Oksana , Chernikov Dmitrii , Razzhivin Vasilii , Yusupov Rinat
Published: November 2023

This research paper addresses the issues in evaluating the effectiveness of magnetic-pulse treatment for healing continuity defects in the metal of oil and gas pipelines. A theoretical analysis of the magnetic-pulse action mechanism on continuity defects in the metal was carried out. The results of experimental studies of the effect of magnetic-pulse action on continuity defects of thick-walled samples, cut from used gas pipelines containing microcracks with different geometries, are also presented. The samples were processed under two different technological operating modes of the magnetic-pulse unit: the applied energy was 10 kJ for the first mode and 20 kJ for the second mode. The state of the cracks’ microstructure before and after the magnetic pulse treatment was studied using an optical microscope. As a result of the studies, it was found that magnetic-pulse treatment led to local heating of the crack tips, which was confirmed by the formation of a heat-affected zone in the vicinity of the crack tips. The temperature at the crack tips reached the metal’s melting point at the applied energy of 20 kJ, whereas at the energy of 10 kJ, signs of metal melting were not noted. In the course of the conducted experiments, it was found that the cracks were not completely eliminated after magnetic-pulse treatment; however, the edges of the crack tips melted, with subsequent filling by molten material. Magnetic-pulse treatment resulted in blunting of the crack tips, as their shape became smoother. It was established that the geometry and shape of the crack tip have significant influences on the effectiveness of this technology, as a narrow and sharp crack tip required less energy to reach the metal’s melting point compared to smoother one. The effect of magnetic pulse treatment on the microstructure of pipeline metal and its strength characteristics was also studied. It was found that this treatment leads to structural changes in the area of the crack tip in the form of grain refinement and subsequent strengthening of the pipeline metal.
Finite Element Modeling Aspects of Buried Large Diameter Steel Pipe–Butterfly Valve Interaction
Authors: Daradkeh Ashraf Mohammed , Jalali Himan Hojat
Published: November 2023

Buried flexible pipes are allowed to deflect up to 2–5% of the pipe diameter, which can become problematic for the connected direct-bury, large-diameter butterfly valves. The complex behavior of the pipe–valve–soil system makes it difficult to predict the deflection of the pipe/valve system. In the absence of field/experimental studies, the application of finite element analysis (FEA) seems necessary to predict deflection and stresses and to avoid potential downtime associated with disruption of service. This paper described the FEA of a large-diameter pipe–valve system, with different backfills under gravity, overburden, and internal pressure loads. The effects of modeling different components of the system (e.g., flanges, bearing housing, gate disc, etc.) were described and investigated. The goal of this study was to provide insight into the design and installation of direct-bury pipe–valve systems and evaluate current installation methods in the absence of guidelines. In addition, the level of modeling details required for FEA to yield accurate results was discussed.
Some Aspects of α-(Acyloxy)alkyl Radicals in Organic Synthesis
Authors: Quiclet-Sire Béatrice , Zard Samir Z.
Published: November 2023

The preparation and use of α-(acyloxy)alkyl xanthates to generate and capture α-(acyloxy)alkyl radicals is briefly reviewed. Their inter- and intramolecular additions to both activated and unactivated, electronically unbiased, alkenes, and to (hetero)aromatic rings, as well as their radical allylation and vinylation reactions are described. Application to the total synthesis of two 4-hydroxytetralone natural products is also presented.
Bio-SELEX: A Strategy for Biomarkers Isolation Directly from Biological Samples
Authors: Ospina-Villa Juan David , Restrepo-Cano Valentina , Sánchez-Jiménez Miryan Margot
Published: November 2023

Bio-SELEX is a revolutionary method for the discovery of novel biomarkers within biological samples, offering profound insights into diagnosing both infectious and non-infectious diseases. This innovative strategy involves three crucial steps: Traditional SELEX, Pull Down, and mass spectrometry. Firstly, Traditional SELEX involves the systematic selection of specific nucleic acid sequences (aptamers) that bind to the target molecules of interest. These aptamers are generated through iterative rounds of selection, amplification, and enrichment, ultimately yielding highly selective ligands. Secondly, the Pull-Down phase employs these aptamers to capture and isolate the target biomarkers from complex biological samples. This step ensures the specificity of the selected aptamers in binding to their intended targets. Lastly, mass spectrometry is utilized to identify and quantify the captured biomarkers, providing precise information about their presence and concentration in the sample. These quantitative data are invaluable in disease diagnosis and monitoring. Bio-SELEX’s significance lies in its ability to discover biomarkers for a wide range of diseases, spanning infectious and non-infectious conditions. This approach holds great promise for early disease detection, personalized medicine, and the development of targeted therapies. By harnessing the power of aptamers and mass spectrometry, Bio-SELEX advances our understanding of disease biology and opens new avenues for improved healthcare.