bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability Evaluation of a Dynamic-Pressure Mechanical Seal Based on Liquid Film Vaporization Phase Transition
Authors: Bei Guangyao , Xu Xiaodong , Ma Chenbo , Sun Jianjun , Zhang Yuyan , Yu Qiuping
Published: February 2024

Aiming at the problem of researching the reliability of dynamic-pressure mechanical seals, this paper proposes a reliability evaluation method for dynamic-pressure mechanical seals based on the Monte Carlo method. Based on the influence of the mass transfer coefficient on vaporization phase transition, a liquid film vaporization model of a hydrodynamic mechanical seal’s end face is established, and the working condition parameters and groove structure parameters are designed using the experimental design method. The vaporization characteristics of the liquid film under various parameters are analyzed, and the functional functions of the vaporization characteristics are obtained by fitting. Combined with the maximum vapor phase volume fraction when the dynamic-pressure mechanical seal changes from the liquid miscible phase to the vapor miscible phase, the limit state equation of the vapor phase volume fraction is obtained. Finally, based on the Monte Carlo simulation method, the sealing reliability under specific groove structure parameters is calculated. Our research shows that this method has practicability and effectiveness for the reliability evaluation of mechanical seals with different working conditions and different groove structures.
Polymorphisms in M2+AlF5(H2O)7 (M2+ = Fe2+, Co2+, or Ni2+): Syntheses, Crystal Structures, and Characterization of New Mixed Metal Fluoride Hydrates
Authors: Seo Jun Min , Jo Hongil , Choi Myung Ho , Ok Kang Min , Chang Hong Young , Kim Sun Woo
Published: February 2024

Three new mixed metal fluoride hydrates, M2+AlF5(H2O)7 (M2+ = Fe2+, Co2+, or Ni2+), were synthesized and characterized. The crystals of M2+AlF5(H2O)7 were obtained using a hydrothermal method with a CF3COOH aqueous solution. The crystal structures displayed polymorphisms in C2/m (No. 12) or P-1 (No. 2) space groups, depending on temperature variations. The observed polymorphisms in M2+AlF5(H2O)7 are associated with changes in the bonding environment of [M(H2O)6]2+ and [AlF5(H2O)]2− octahedra, along with changes in hydrogen bonds and unit cell volumes. Infrared spectra and thermogravimetric analyses confirmed the presence of water molecules. The ultraviolet–visible spectra of M2+AlF5(H2O)7 revealed distinctive absorption bands dependent on the [M(H2O)6]2+ complex. This work provides a detailed account of the synthetic procedure, crystal structures, and spectroscopic characterization of M2+AlF5(H2O)7.
Eye-Tracking Analysis of Proposed Signage Design to Prevent Accidents Caused by the Abrupt Appearance of Dividers on Indian Roads
Authors: Desai Manohar , Chowdhury Anirban
Published: February 2024

The road transport system is expanding considerably in developing countries. Villages are connecting to major cities for business, education, health, and many other reasons because of road development and smooth transportation. There has been a rise in the number of road accidents observed, caused by abruptly appearing dividers on roads and a lack of required signage systems. This paper discusses scenarios of accidents due to such abruptly appearing dividers and offers a strategy to design appropriate signage to avoid road accidents in the future. It has been observed that permanent or movable arbitrary fixtures, such as a barricade or a small partition block wall, are installed to separate lanes, in addition to white-colored stripes that are typically employed for lane separation on roads. These fixtures, although they are intended as lane-dividing solutions on roads, cause serious, and at times, fatal accidents, due their sudden, uninitiated appearance on the road. To address this problem, alternative signage designs were designed and tested on Indian roads, based on human cognitive responses and visual attention analysis on signage using an eye-tracking method. In addition, the semantic quality and legibility of alternate signage designs were evaluated using a questionnaire to judge their overall efficacy. Hence, the best signage design solution is proposed for implementation near or before occurrences of road dividers to avoid accidents.
Gas Kinetic Scheme Coupled with High-Speed Modifications for Hypersonic Transition Flow Simulations
Authors: Li Chengrui , Zhao Wenwen , Liu Hualin , Xue Youtao , Yang Yuxin , Chen Weifang
Published: February 2024

The issue of hypersonic boundary layer transition prediction is a critical aerodynamic concern that must be addressed during the aerodynamic design process of high-speed vehicles. In this context, we propose an advanced mesoscopic method that couples the gas kinetic scheme (GKS) with the Langtry–Menter transition model, including its three high-speed modification methods, tailored for accurate predictions of high-speed transition flows. The new method incorporates the turbulent kinetic energy term into the Maxwellian velocity distribution function, and it couples the effects of high-speed modifications on turbulent kinetic energy within the computational framework of the GKS solver. This integration elevates both the transition model and its high-speed enhancements to the mesoscopic level, enhancing the method’s predictive capability. The GKS-coupled mesoscopic method is validated through a series of test cases, including supersonic flat plate simulation, multiple hypersonic cone cases, the Hypersonic International Flight Research Experimentation (HIFiRE)-1 flight test, and the HIFiRE-5 case. The computational results obtained from these cases exhibit favorable agreement with experimental data. In comparison with the conventional Godunov method, the new approach encompasses a broader range of physical mechanisms, yielding computational results that closely align with the true physical phenomena and marking a notable elevation in computational fidelity and accuracy. This innovative method potentially satisfies the compelling demand for developing a precise and rapid method for predicting hypersonic boundary layer transition, which can be readily used in engineering applications.
Solvation Thermodynamics and Its Applications
Authors: Ben-Naim Arieh
Published: February 2024

In this article, we start by describing a few “definitions” of the solvation processes, which were used in the literature until about 1980. Then, we choose one of these definitions and show that it has a simple molecular interpretation. This fact led to a new definition of the solvation process and the corresponding thermodynamic quantities. The new measure of the solvation Gibbs energy has a simple interpretation. In addition, the thermodynamic quantities associated with the new solvation process have several other advantages over the older measures. These will be discussed briefly in the third section. In the fourth section, we discuss a few applications of the new solvation process.
Non-Digital Games That Promote Mathematical Learning in Primary Years Students: A Systematic Review
Authors: Russo James , Kalogeropoulos Penelope , Bragg Leicha A. , Heyeres Marion
Published: February 2024

Despite primary school teachers demonstrating strong preferences for using non-digital games over digital games to support mathematics instruction, much of the research review literature has focused on learning outcomes associated with digital mathematical games. To address this gap, the current systematic literature review focuses on non-digital, games-based, empirical studies in the primary mathematics classroom over the past two decades from 2003 to 2022. The Preferred Reporting Items for Systematic Reviews (PRISMA) statement was employed as a guideline for the data-collection process. The review presents an analysis and synthesis of 34 manuscripts, representing 32 distinct studies. Over three-quarters of manuscripts employed quantitative methodologies and around half qualitative methodologies, whilst studies focused exclusively on student, as opposed to teacher, outcomes. Despite Australia and Indonesia being comparatively overrepresented, the studies in scope were notable for both their geographic diversity and the eclectic range of game types and structures incorporated; although they did tend to disproportionately focus on number and operations, as opposed to other mathematical content areas. Moreover, the impact of mathematical games was generally positive across the broad range of outcomes considered, suggesting that mathematical games are potentially effective for both developing mathematical proficiencies, as well as improving dispositions towards mathematics. Future research directions are discussed.
Do Good Intentions Lead to Expected Outcomes? Professional Learning Amongst Early Career Academics in a Problem-Based Program
Authors: Stegeager Nikolaj , Traulsen Sofie Jensen , Guerra Aida Olivia Pereira de Carvalho , Telléus Patrik Kristoffer Kjærsdam , Du Xiangyun
Published: February 2024

This paper presents findings from a study of pedagogical beliefs and practices amongst early career academics attending an extensive professional development program. The research questions of this study were as follows: how do early career academics define their pedagogical beliefs in relation to a pedagogical development program, and how do their beliefs manifest in their pedagogical practice? This study was based on a qualitative document analysis of 145 project reports written as the finalizing part of the early career academics’ participation in the program. Reports were collected with the consent of participants, coded, and analyzed to search for emerging pedagogical beliefs and subsequent practices. The findings indicate that while almost all participants express beliefs that are aligned with the core values of the university, their reported practices are quite diverse. Based on this, we propose a framework for understanding teaching development amongst early career academics centered on their individual development and their interaction with students. This framework provides a contribution to our understanding of the teaching trajectories of early career academics and the intricate interplay between pedagogical beliefs and pedagogical practice. This framework may be of use for educational developers when planning and conducting pedagogical development activities.
Efficacy and Antifungal Mechanism of Rosemary Essential Oil against Colletotrichum gloeosporioides
Authors: Yuan Tiantian , Hua Yang , Zhang Dangquan , Yang Chaochen , Lai Yong , Li Mingwan , Ding Shen , Li Song , Chen Yuanyuan
Published: February 2024

The antifungal activity and mechanism of rosemary essential oil against Colletotrichum gloeosporioides, the walnut anthracnose pathogen, were investigated using scanning electron microscopy (SEM), index determination and transcriptome technique. The results showed that rosemary essential oil could inhibit the growth of C. gloeosporioides with minimum inhibitory (MIC) and fungicidal (MFC) concentrations of 15.625 μL/mL and 31.25 μL/mL, respectively. Scanning electron microscopy revealed that the mycelium morphology became shriveled, twisted, and severely deformed after being treated with rosemary essential oil. The activity of chitinase, which decomposes fungal cell wall components in C. gloeosporioides, increased. The ergosterol content in the plasma membrane decreased, while the cell contents including nucleic acids, soluble protein and soluble reducing sugar were released resulting in the extracellular electrical conductivity being changed. For metabolic activity, the enzymes succinate dehydrogenase (SDH), malate dehydrogenase (MDH), ATPase and ATP decreased, whereas phosphofructokinase (PFK) increased. Transcriptome sequencing results showed that the antifungal mechanism of rosemary essential oil involves the destruction of the cell wall and membrane, inhibition of genetic material synthesis, and cell division and differentiation. The results are helpful to understand the efficacy and antifungal mechanism of rosemary essential oil against C. gloeosporioides and provide a theoretical basis for the development of rosemary essential oil as a biological control agent.
Evaluating Dendrolimus superans (Lepidoptera: Lasiocampidae) Occurrence and Density Modeling with Habitat Conditions
Authors: Han Daxiao , Wang Shuo , Zhang Jili , Cui Rong , Wang Qianxue
Published: February 2024

Dendrolimus superans, a prominent forest pest in northeast China, exerts detrimental effects on tree growth and development, disrupts the ecological functioning of forests, and even alters the trajectory of succession. The objective of this study was to investigate the influence of habitat conditions on the occurrence probability and density of overwintering D. superans, aiming to provide scientific insights for the effective prevention of and control measures against this pest infestation. The investigation encompassed 142 plots (20 m × 20 m) in various forest types within the primary distribution area of D. superans in the Great Xing’ an Mountains, focusing on factors such as topography, forest vegetation, and larval density. Binary logistic regression was employed to establish models for predicting the occurrence probability of D. superans, while generalized linear models (GLMs) and categorical regression (CATREG) were utilized to develop models for estimating its population size. Subsequently, an evaluation was conducted to assess the performance of these models. The occurrence probability model showed high accuracy (AUC = 0.826) in predicting infestation. The slope aspect and herb cover were the key factors affecting the occurrence of D. superans. The occurrence probability was the lowest on shady slopes and the highest on sunny slopes. The occurrence probability of D. superans increased with the increase in herb cover. The model of quantification showed that the density of D. superans was the least on shady slopes and the highest on sunny slopes. As the slope gradient increased, the density decreased. D. superans occurred most frequently on ridges. Similarly, with the increase in canopy cover or the decrease in diameter at breast height (DBH) and stand density, the density of D. superans increased. The influence of the topography factors surpassed that of the forest vegetation factors in shaping the population dynamics of D. superans, despite both being significant contributors. The study revealed that D. superans is prone to occur on sunny slopes, flat slopes, and ridges, which should be the focus of prevention and control in forest management practices, such as replanting, thinning, and regular weeding, to help restrain the growth of the population of this pest.
An Assessment Framework for Mapping the Air Purification Service of Vegetation at the Regional Scale
Authors: Liu Yu , Zhao Wudong , Zhang Liwei , Li Xupu , Peng Lixian , Wang Zhuangzhuang , Song Yongyong , Jiao Lei , Wang Hao
Published: February 2024

Efficiently mitigating the severe air pollution resulting from rapid progress is crucial for the sustainable development of the socio-ecological system. Recently, concerns about nature-based solutions have emerged in the research on the treatment of air pollution. Studies on the purification of PM2.5 using vegetation currently concentrate on the individual scale of tree species or urban vegetation, ignoring the regional scale, which could better assist ecological governance. Therefore, taking the Fenwei Plain of China as the study area, an assessment framework of the air purification service’s spatial distribution reflecting regional vegetation was constructed. The dry deposition model and GeoDetector were used to quantify the spatial-temporal pattern and explore natural driving factors on the removal of PM2.5. The results showed that (1) the PM2.5 purification services offered by various types of vegetation exhibit notable variations. The average removal rates of PM2.5 by vegetation were 0.186%, 0.243%, and 0.435% in 2000, 2010, and 2021, respectively. (2) Meanwhile, a wide range of spatial mismatch exists between the PM2.5 concentration and PM2.5 removal. Insufficient supply regions of PM2.5 purification services account for 50% of the Fenwei Plain. (3) PM2.5 removal was strongly influenced by the types of vegetation and the Normalized Vegetation Index (NDVI), followed by the Digital Elevation Model (DEM), and less affected by meteorological factors; a strong joint effect was shown among the factors. The findings in this research provide a new perspective on regional air pollution management at the regional scale.
Effect of Spray-Type Alginate Hydrogel Dressing on Burn Wounds
Authors: Choi Jeong Yeon , Joo Yong-Joon , Kang Ri Jin , Jeon Hee Kyung , Hong Gyeong Sik
Published: February 2024

Immediate burn wound care is a critical factor influencing the outcomes of burn treatment. In this study, we developed a spray-type alginate hydrogel dressing that promotes wound healing, reduces pain, and increases the convenience of use in a burn treatment emergency. We investigated the efficiency of newly developed spray-type alginate hydrogel dressing on the wound healing process. We investigated the efficacy of the alginate hydrogel dressing for wound healing in 30 Sprague Dawley rats. Four deep, round second-degree burn wounds (diameter, 1.5 cm) were created bilaterally on the dorsum of the rat’s trunk; the rats were divided into four groups, in which different dressing materials were applied as follows: group A, gauze (control); group B, Mepilex™ (control); group C, 2.25% alginate hydrogel; and group D, 2.5% alginate hydrogel. The gross findings of each group were compared by tracing the remaining wound and performing visual and histological observations and biochemical analysis for proteins associated with wound healing at each time period. In burn wounds, groups C and D showed significantly higher contraction, epithelialization, and healing rates. Histologically, groups C and D showed an improved arrangement of collagen fibers and a thick epithelial layer 14 days after initial wound formation. Group C showed higher CD31, TGF-β, and fibronectin expression in Western blot analyses after day 14. This study suggests that the spray-type alginate hydrogel dressing is an effective material for initial burn wound care.
Long-Term Quality of Life after COVID-19 Infection: Cross-Sectional Study of Health Care Workers
Authors: Antar Moussa , Ullerich Hansjoerg , Zaruchas Andreas , Meier Torsten , Diller Ricarda , Pannewick Ulrich , Dhayat Sameer A.
Published: February 2024

(1) Background: Post-COVID syndrome is defined as symptoms that occur simultaneously with or after a COVID-19 infection, last for 12 weeks, and are not due to another diagnosis. Limited data are available on people’s long-term quality of life following a COVID-19 infection. The aim of this cross-sectional study was to investigate the long-term quality of life after COVID-19 among employees of a hospital in Germany and to identify risk factors. (2) Methods: A monocentric, cross-sectional study was conducted using the validated and digitized WHOQOL-BREF questionnaire via Netigate® between 10/2022 and 02/2023. Data on the quality of life and global health status were collected in the following four domains: physical health, mental health, social relationships, and the environment. (3) Results: The response rate was 73.8 % (923/1250). Furthermore, 63.4 % of the hospital staff respondents reported at least one persistent symptom after a COVID-19 infection, leading to significant differences in quality of life. Pre-existing conditions, persistent symptoms, and disabilities after a COVID-19 infection as well as a high BMI, no partnership, and a low educational level were found to significantly contribute to a low long-term quality of life. (4) Conclusions: Obesity, a lack of partnership, and a low level of education were independent risk factors for a lower quality of life post-COVID-19 infection in this cohort of hospital staff. Further multicenter studies are required to validate the incidence and their suitability as independent risk factors for post-COVID syndrome.
A Survey on the Expression of the Ubiquitin Proteasome System Components HECT- and RBR-E3 Ubiquitin Ligases and E2 Ubiquitin-Conjugating and E1 Ubiquitin-Activating Enzymes during Human Brain Development
Authors: Magnati Stefano , Alladio Eugenio , Bracco Enrico
Published: February 2024

Human brain development involves a tightly regulated sequence of events that starts shortly after conception and continues up to adolescence. Before birth, neurogenesis occurs, implying an extensive differentiation process, sustained by changes in the gene expression profile alongside proteome remodeling, regulated by the ubiquitin proteasome system (UPS) and autophagy. The latter processes rely on the selective tagging with ubiquitin of the proteins that must be disposed of. E3 ubiquitin ligases accomplish the selective recognition of the target proteins. At the late stage of neurogenesis, the brain starts to take shape, and neurons migrate to their designated locations. After birth, neuronal myelination occurs, and, in parallel, neurons form connections among each other throughout the synaptogenesis process. Due to the malfunctioning of UPS components, aberrant brain development at the very early stages leads to neurodevelopmental disorders. Through deep data mining and analysis and by taking advantage of machine learning-based models, we mapped the transcriptomic profile of the genes encoding HECT- and ring-between-ring (RBR)-E3 ubiquitin ligases as well as E2 ubiquitin-conjugating and E1 ubiquitin-activating enzymes during human brain development, from early post-conception to adulthood. The inquiry outcomes unveiled some implications for neurodevelopment-related disorders.
Oxolane Ammonium Salts (Muscarine-Like)—Synthesis and Microbiological Activity
Authors: Bogdanowicz Patrycja , Madaj Janusz , Szweda Piotr , Sikorski Artur , Samaszko-Fiertek Justyna , Dmochowska Barbara
Published: February 2024

Commercially available 2-deoxy-D-ribose was used to synthesize the appropriate oxolane derivative—(2R,3S)-2-(hydroxymethyl)oxolan-3-ol—by reduction and dehydration/cyclization in an acidic aqueous solution. Its monotosyl derivative, as a result of the quaternization reaction, allowed us to obtain eight new muscarine-type derivatives containing a quaternary nitrogen atom and a hydroxyl group linked to the oxolane ring. Their structure was fully confirmed by the results of NMR, MS and IR analyses. The crystal structure of the pyridinium derivative showed a high similarity of the conformation of the oxolane ring to previously published crystal structures of muscarine. Two reference strains of Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853), two reference strains of Gram-positive staphylococci (Staphylococcus aureus ATCC 25923 and Staphylococcus aureus ATCC 29213) and four reference strains of pathogenic yeasts of the genus Candida spp. (Candida albicans SC5314, Candida glabrata DSM 11226, Candida krusei DSM 6128 and Candida parapsilosis DSM 5784) were selected for the evaluation of the antimicrobial potential of the synthesized compounds. The derivative containing the longest (decyl) chain attached to the quaternary nitrogen atom turned out to be the most active.
Deciphering Early-Stage Molecular Mechanisms of Negative Pressure Wound Therapy in a Murine Model
Authors: Shyu Yu-Chiau , Huang Ting-Shuo , Chiu Hua-Sheng , Sumazin Pavel , Lin Xin-Yu , Liao Po-Cheng , Liou Cai-Cin , Hsu Fang-Chia , Lin Jyuan-Siou , Hsu Chih-Chin , Hsu Pang-Hung , Sun Chi-Chin , Chen Chien-Tzung
Published: February 2024

Negative Pressure Wound Therapy (NPWT) is a commonly employed clinical strategy for wound healing, yet its early-stage mechanisms remain poorly understood. To address this knowledge gap and overcome the limitations of human trials, we establish an NPWT C57BL/6JNarl mouse model to investigate the molecular mechanisms involved in NPWT. In this study, we investigate the intricate molecular mechanisms through which NPWT expedites wound healing. Our focus is on NPWT’s modulation of inflammatory immune responses and the concurrent orchestration of multiple signal transduction pathways, resulting in shortened coagulation time and reduced inflammation. Notably, we observe a significant rise in dickkopf-related protein 1 (DKK-1) concentration during NPWT, promoting the differentiation of Hair Follicle Stem Cells (HFSCs) into epidermal cells, expediting wound closure. Under negative pressure, macrophages express and release DKK-1 cytokines, crucial for stimulating HFSC differentiation, as validated in animal experiments and in vitro studies. Our findings illuminate the inflammatory dynamics under NPWT, revealing potential signal transduction pathways. The proposed framework, involving early hemostasis, balanced inflammation, and macrophage-mediated DKK-1 induction, provides a novel perspective on enhancing wound healing during NPWT. Furthermore, these insights lay the groundwork for future pharmacological advancements in managing extensive wounds, opening avenues for targeted therapeutic interventions in wound care.
The Complement Component 4 Binding Protein α Gene: A Versatile Immune Gene That Influences Lipid Metabolism in Bovine Mammary Epithelial Cell Lines
Authors: Chen Xuanxu , Zhao Zhihui , Jiang Xinyi , Li Jing , Miao Fengshuai , Yu Haibin , Lin Ziwei , Jiang Ping
Published: February 2024

Complement component 4 binding protein α (C4BPA) is an immune gene which is responsible for the complement regulation function of C4BP by binding and inactivating the Complement component C4b (C4b) component of the classical Complement 3 (C3) invertase pathway. Our previous findings revealed that C4BPA was differentially expressed by comparing the transcriptome in high-fat and low-fat bovine mammary epithelial cell lines (BMECs) from Chinese Holstein dairy cows. In this study, a C4BPA gene knockout BMECs line model was constructed via using a CRISPR/Cas9 system to investigate the function of C4BPA in lipid metabolism. The results showed that levels of triglyceride (TG) were increased, while levels of cholesterol (CHOL) and free fatty acid (FFA) were decreased (p < 0.05) after knocking out C4BPA in BMECs. Additionally, most kinds of fatty acids were found to be mainly enriched in the pathway of the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, fatty acid biosynthesis, and regulation of lipolysis in adipocyte. Meanwhile, the RNA-seq showed that most of the differentially expressed genes (DEGs) are related to PI3K-Akt signaling pathway. The expressions of 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 (HMGCS1), Carnitine Palmitoyltransferase 1A (CPT1A), Fatty Acid Desaturase 1 (FADS1), and Stearoyl-Coenzyme A desaturase 1 (SCD1) significantly changed when the C4BPA gene was knocked out. Collectively, C4BPA gene, which is an immune gene, played an important role in lipid metabolism in BMECs. These findings provide a new avenue for animal breeders: this gene, with multiple functions, should be reasonably utilized.
Association between Brain-Derived Neurotrophic Factor and Lipid Profiles in Acute Ischemic Stroke Patients
Authors: Tuwar Mayuri N. , Chen Wei-Hung , Yeh Hsu-Ling , Bai Chyi-Huey
Published: February 2024

Ischemic stroke, the most prevalent form of stroke, leads to neurological impairment due to cerebral ischemia and affects 55–90% of the population. Brain-derived neurotrophic factor (BDNF) plays a crucial role in the central nervous system and regulates cardiometabolic risk factors, including lipids. This single-center study aimed to explore the relationship between lipid profiles and BDNF levels in 90 patients who had experienced AIS for the first time. The results show that the high BDNF group (≥3.227 ng/mL) had significantly higher HbA1C and TG levels; ratios of TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C; and percentage of hyperlipidemia (60%) as well as lower levels of HDL-C, with an OR of 1.903 (95% CI: 1.187–3.051) for TG/HDL-C, 1.975 (95% CI: 1.188–3.284) for TC/HDL-C, and 2.032 (95% CI: 1.113–3.711) for LDL-C/HDL-C. Plasma BDNF levels were found to be significantly positively correlated with TG and negatively with HDL-C, with OR values of 1.017 (95% CI: 1.003–1.030) and 0.926 (95% CI: 0.876–0.978), respectively. TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C ratios are associated with BDNF levels in AIS patients. The results also indicate that, in AIS patients, higher BDNF levels are associated with lower HDL and higher TG concentrations.
Genetic Landscape of Factor VII Deficiency: Insights from a Comprehensive Analysis of Pathogenic Variants and Their Impact on Coagulation Activity
Authors: Preisler Barbara , Pezeshkpoor Behnaz , Merzenich Anja , Ohlenforst Sandra , Rühl Heiko , Ivaškevičius Vytautas , Scholz Ute , Bönigk Hagen , Eberl Wolfgang , Zieger Barbara , Pavlova Anna , Oldenburg Johannes
Published: February 2024

Congenital factor VII (FVII) deficiency is a rare genetic bleeding disorder characterized by deficient or reduced activity of coagulation FVII. It is caused by genetic variants in the F7 gene. We aimed to evaluate the rate of detection of pathogenic variants in the F7 gene in a large group of patients with FVII deficiency and investigate the correlations between the F7 genotype and FVII activity (FVII:C). Moreover, the influence of the common genetic variant rs6046: c.1238G>A; p.(Arg413Gln), designated as the M2 allele, on FVII:C was investigated. Genetic analysis of the F7 gene was performed on 704 index patients (IPs) using either direct Sanger- or next-generation sequencing. Genetic variants were detected in 390 IPs, yielding a variant detection rate (VDR) of 55%. Notably, the VDR exhibited a linear decline with increasing FVII:C levels. We identified 124 genetic variants, of which 48 were not previously reported. Overall, the frequency of the M2 allele was considerably higher in patients with mild deficiency (FVII:C > 20 IU/dl). Furthermore, IPs lacking an identified pathogenic variant exhibited a significantly higher prevalence of the M2 allele (69%) compared to IPs with a disease-causing variant (47%). These results strongly support the association of the M2 allele with decreased FVII:C levels. This study shows the utility of FVII:C as a predictive marker for identifying pathogenic variants in patients with FVII deficiency. The M2 allele contributes to the reduction of FVII:C levels, particularly in cases of mild deficiency.
The Promising B−Type Response Regulator hst1 Gene Provides Multiple High Temperature and Drought Stress Tolerance in Rice
Authors: Lopes Hornai Ermelinda Maria Lopes , Aycan Murat , Mitsui Toshiaki
Published: February 2024

High temperatures, drought, and salt stresses severely inhibit plant growth and production due to the effects of climate change. The Arabidopsis ARR1, ARR10, and ARR12 genes were identified as negative salt and drought stress regulators. However, in rice, the tolerance capacity of the hst1 gene, which is orthologous to the ARR1, ARR10, and ARR12 genes, to drought and multiple high temperature and drought stresses remains unknown. At the seedling and reproductive stages, we investigated the drought (DS) high temperature (HT) and multiple high temperature and drought stress (HT+DS) tolerance capacity of the YNU31−2−4 (YNU) genotype, which carries the hst1 gene, and its nearest genomic relative Sister Line (SL), which has a 99% identical genome without the hst1 gene. At the seedling stage, YNU demonstrated greater growth, photosynthesis, antioxidant enzyme activity, and decreased ROS accumulation under multiple HT+DS conditions. The YNU genotype also demonstrated improved yield potential and grain quality due to higher antioxidant enzyme activity and lower ROS generation throughout the reproductive stage under multiple HT+DS settings. Furthermore, for the first time, we discovered that the B−type response regulator hst1 gene controls ROS generation and antioxidant enzyme activities by regulating upstream and downstream genes to overcome yield reduction under multiple high temperatures and drought stress. This insight will help us to better understand the mechanisms of high temperature and drought stress tolerance in rice, as well as the evolution of tolerant crops that can survive increased salinity to provide food security during climate change.
The Effect of Water Co-Feeding on the Catalytic Performance of Zn/HZSM-5 in Ethylene Aromatization Reactions
Authors: Shao Jiabei , Feng Pengcheng , Li Baichao , Gao Jie , Chen Yanyan , Dong Mei , Qin Zhangfeng , Fan Weibin , Wang Jianguo
Published: February 2024

During the methanol-to-aromatics (MTA) process, a large amount of water is generated, while the influence and mechanism of water on the activity and selectivity of the light olefin aromatization reaction are still unclear. Therefore, a study was conducted to systematically investigate the effects of water on the reactivity and the product distribution in ethylene aromatization using infrared spectroscopy (IR), intelligent gravitation analyzer (IGA), and X-ray absorption fine structure (XAFS) characterizations. The results demonstrated that the presence of water reduced ethylene conversion and aromatic selectivity while increasing hydrogen selectivity at the same contact time. This indicated that water had an effect on the reaction pathway by promoting the dehydrogenation reaction and suppressing the hydrogen transfer reaction. A detailed analysis using linear combination fitting (LCF) of Zn K-edge X-ray absorption near-edge spectroscopy (XANES) on Zn/HZSM-5 catalysts showed significant variations in the state of existence and the distribution of Zn species on the deactivated catalysts, depending on different reaction atmospheres and water contents. The presence of water strongly hindered the conversion of ZnOH+ species, which served as the active centers for the dehydrogenation reaction, to ZnO on the catalyst. As a result, the dehydrogenation activity remained high in the presence of water. This study using IR and IGA techniques revealed that water on the Zn/HZSM-5 catalyst inhibited the adsorption of ethylene on the zeolite, resulting in a noticeable decrease in ethylene conversion and a decrease in aromatic selectivity. These findings contribute to a deeper understanding of the aromatization reaction process and provide data support for the design of efficient aromatization catalysts.
Prefoldin-5 Expression Is Elevated in Eutopic and Ectopic Endometriotic Epithelium and Modulates Endometriotic Epithelial Cell Proliferation and Migration In Vitro
Authors: Nothnick Warren B. , Cui Wei , Falcone Tommaso , Graham Amanda
Published: February 2024

Endometriosis is a common disease among women of reproductive age in which endometrial tissue grows in ectopic localizations, primarily within the pelvic cavity. These ectopic “lesions” grow as well as migrate and invade underlying tissues. Despite the prevalence of the disease, an understanding of factors that contribute to these cellular attributes remains poorly understood. Prefoldin-5 (PFDN5) has been associated with both aberrant cell proliferation and migration, but a potential role in endometriosis is unknown. As such, the purpose of this study was to examine PFDN5 expression in endometriotic tissue. PFDN5 mRNA and protein were examined in ectopic (lesion) and eutopic endometrial tissue from women with endometriosis and in eutopic endometrium from those without endometriosis using qRT-PCR and immunohistochemistry, respectively, while function of PFDN5 in vitro was evaluated using cell count and migration assays. PFDN5 mRNA and protein were expressed in eutopic and ectopic endometrial tissue, predominantly in the glandular epithelium, but not in endometrium from control subjects. Expression of both mRNA and protein was variable among endometriotic eutopic and ectopic endometrial tissue but showed an overall net increase. Knockdown of PFDN5 by siRNA transfection of endometriotic epithelial 12Z cells was associated with reduced cell proliferation/survival and migration. PFDN5 is expressed in eutopic and ectopic glandular epithelium and may play a role in proliferation and migration of these cells contributing to disease pathophysiology.
Hub Genes and Pathways Related to Lemon (Citrus limon) Leaf Response to Plenodomus tracheiphilus Infection and Influenced by Pseudomonas mediterranea Biocontrol Activity
Authors: Sicilia Angelo , Russo Riccardo , Catara Vittoria , Lo Piero Angela Roberta
Published: February 2024

The lemon industry in the Mediterranean basin is strongly threatened by “mal secco” disease (MSD) caused by the fungus Plenodomus tracheiphlilus. Leaf pretreatments with Pseudomonas mediterranea 3C have been proposed as innovative tools for eco-sustainable interventions aimed at controlling the disease. In this study, by exploiting the results of previously performed RNAseq analysis, WCGNA was conducted among gene expression patterns in both inoculated (Pt) and pretreated and fungus-inoculated lemon plants (Citrus limon L.) (3CPt), and two indicators of fungal infection, i.e., the amount of fungus DNA measured in planta and the disease index (DI). The aims of this work were (a) to identify gene modules significantly associated with those traits, (b) to construct co-expression networks related to mal secco disease; (c) to define the effect and action mechanisms of P. mediterranea by comparing the networks. The results led to the identification of nine hub genes in the networks, with three of them belonging to receptor-like kinases (RLK), such as HERK1, CLAVATA1 and LRR, which play crucial roles in plant–pathogen interaction. Moreover, the comparison between networks indicated that the expression of those receptors is not induced in the presence of P. mediterranea, suggesting how powerful WCGNA is in discovering crucial genes that must undergo further investigation and be eventually knocked out.
Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the “Normobaric Oxygen Paradox”
Authors: Balestra Costantino , Baldelli Sara , Virgili Fabio , Salvagno Michele , Mrakic-Sposta Simona , Fratantonio Deborah
Published: February 2024

The “normobaric oxygen paradox” (NOP) describes the response to the return to normoxia after a hyperoxic event, sensed by tissues as an oxygen shortage, up-regulating redox-sensitive transcription factors. We have previously characterized the time trend of oxygen-sensitive transcription factors in human PBMCs, in which the return to normoxia after 30% oxygen is sensed as a hypoxic trigger, characterized by hypoxia-induced factor (HIF-1) activation. On the contrary, 100% and 140% oxygen induce a shift toward an oxidative stress response, characterized by NRF2 and NF-kB activation in the first 24 h post exposure. Herein, we investigate whether this paradigm triggers Advanced Glycation End products (AGEs) and Advanced Oxidation Protein Products (AOPPs) as circulating biomarkers of oxidative stress. Secondly, we studied if mitochondrial biogenesis was involved to link the cellular response to oxidative stress in human PBMCs. Our results show that AGEs and AOPPs increase in a different manner according to oxygen dose. Mitochondrial levels of peroxiredoxin (PRX3) supported the cellular response to oxidative stress and increased at 24 h after mild hyperoxia, MH (30% O2), and high hyperoxia, HH (100% O2), while during very high hyperoxia, VHH (140% O2), the activation was significantly high only at 3 h after oxygen exposure. Mitochondrial biogenesis was activated through nuclear translocation of PGC-1α in all the experimental conditions. However, the consequent release of nuclear Mitochondrial Transcription Factor A (TFAM) was observed only after MH exposure. Conversely, HH and VHH are associated with a progressive loss of NOP response in the ability to induce TFAM expression despite a nuclear translocation of PGC-1α also occurring in these conditions. This study confirms that pulsed high oxygen treatment elicits specific cellular responses, according to its partial pressure and time of administration, and further emphasizes the importance of targeting the use of oxygen to activate specific effects on the whole organism.
Pharmacological Activation of TRPC6 Channel Prevents Colitis Progression
Authors: Nishiyama Kazuhiro , Kato Yuri , Nishimura Akiyuki , Mi Xinya , Nagata Ryu , Mori Yasuo , Azuma Yasu-Taka , Nishida Motohiro
Published: February 2024

We recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn2+ homeostasis in the heart. Zn2+ has also been implicated in the regulation of intestinal redox and microbial homeostasis. This study aims to investigate the role of TRPC6-mediated Zn2+ influx in the stress resistance of the intestine. The expression profile of TRPC1-C7 mRNAs in the actively inflamed mucosa from inflammatory bowel disease (IBD) patients was analyzed using the GEO database. Systemic TRPC3 knockout (KO) and TRPC6 KO mice were treated with dextran sulfate sodium (DSS) to induce colitis. The Zn2+ concentration and the mRNA expression levels of oxidative/inflammatory markers in colon tissues were quantitatively analyzed, and gut microbiota profiles were compared. TRPC6 mRNA expression level was increased in IBD patients and DSS-treated mouse colon tissues. DSS-treated TRPC6 KO mice, but not TRPC3 KO mice, showed severe weight loss and increased disease activity index compared with DSS-treated WT mice. The mRNA abundances of antioxidant proteins were basically increased in the TRPC6 KO colon, with changes in gut microbiota profiles. Treatment with TRPC6 activator prevented the DSS-induced colitis progression accompanied by increasing Zn2+ concentration. We suggest that TRPC6-mediated Zn2+ influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.
Intravenous Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Spinal Cord Injury by Regulating Neutrophil Extracellular Trap Formation through Exosomal miR-125a-3p
Authors: Morishima Yutaka , Kawabori Masahito , Yamazaki Kazuyoshi , Takamiya Soichiro , Yamaguchi Sho , Nakahara Yo , Senjo Hajime , Hashimoto Daigo , Masuda Sakiko , Fujioka Yoichiro , Ohba Yusuke , Mizuno Yuki , Kuge Yuji , Fujimura Miki
Published: February 2024

Spinal cord injury (SCI) leads to devastating sequelae, demanding effective treatments. Recent advancements have unveiled the role of neutrophil extracellular traps (NETs) produced by infiltrated neutrophils in exacerbating secondary inflammation after SCI, making it a potential target for treatment intervention. Previous research has established that intravenous administration of stem cell-derived exosomes can mitigate injuries. While stem cell-derived exosomes have demonstrated the ability to modulate microglial reactions and enhance blood–brain barrier integrity, their impact on neutrophil deactivation, especially in the context of NETs, remains poorly understood. This study aims to investigate the effects of intravenous administration of MSC-derived exosomes, with a specific focus on NET formation, and to elucidate the associated molecular mechanisms. Exosomes were isolated from the cell supernatants of amnion-derived mesenchymal stem cells using the ultracentrifugation method. Spinal cord injuries were induced in Sprague-Dawley rats (9 weeks old) using a clip injury model, and 100 μg of exosomes in 1 mL of PBS or PBS alone were intravenously administered 24 h post-injury. Motor function was assessed serially for up to 28 days following the injury. On Day 3 and Day 28, spinal cord specimens were analyzed to evaluate the extent of injury and the formation of NETs. Flow cytometry was employed to examine the formation of circulating neutrophil NETs. Exogenous miRNA was electroporated into neutrophil to evaluate the effect of inflammatory NET formation. Finally, the biodistribution of exosomes was assessed using 64Cu-labeled exosomes in animal positron emission tomography (PET). Rats treated with exosomes exhibited a substantial improvement in motor function recovery and a reduction in injury size. Notably, there was a significant decrease in neutrophil infiltration and NET formation within the spinal cord, as well as a reduction in neutrophils forming NETs in the circulation. In vitro investigations indicated that exosomes accumulated in the vicinity of the nuclei of activated neutrophils, and neutrophils electroporated with the miR-125a-3p mimic exhibited a significantly diminished NET formation, while miR-125a-3p inhibitor reversed the effect. PET studies revealed that, although the majority of the transplanted exosomes were sequestered in the liver and spleen, a notably high quantity of exosomes was detected in the damaged spinal cord when compared to normal rats. MSC-derived exosomes play a pivotal role in alleviating spinal cord injury, in part through the deactivation of NET formation via miR-125a-3p.
Primary Human M2 Macrophage Subtypes Are Distinguishable by Aqueous Metabolite Profiles
Authors: Fuchs Amanda L. , Costello Stephanann M. , Schiller Sage M. , Tripet Brian P. , Copié Valérie
Published: February 2024

The complexity of macrophage (MΦ) plasticity and polarization states, which include classically activated pro-inflammatory (M1) and alternatively activated anti-inflammatory (M2) MΦ phenotypes, is becoming increasingly appreciated. Within the M2 MΦ polarization state, M2a, M2b, M2c, and M2d MΦ subcategories have been defined based on their expression of specific cell surface receptors, secreted cytokines, and specialized immune effector functions. The importance of immunometabolic networks in mediating the function and regulation of MΦ immune responses is also being increasingly recognized, although the exact mechanisms and extent of metabolic modulation of MΦ subtype phenotypes and functions remain incompletely understood. In this study, proton (1H) nuclear magnetic resonance (NMR) metabolomics was employed to determine the polar metabolomes of M2 MΦ subtypes and to investigate the relationship between aqueous metabolite profiles and M2 MΦ functional phenotypes. Results from this study demonstrate that M2a MΦs are most distinct from M2b, M2c, and M2d MΦ subtypes, and that M2b MΦs display several metabolic traits associated with an M1-like MΦ phenotype. The significance of metabolome differences for metabolites implicated in glycolysis, the tricarboxylic acid (TCA) cycle, phospholipid metabolism, and creatine–phosphocreatine cycling is discussed. Altogether, this study provides biochemical insights into the role of metabolism in mediating the specialized effector functions of distinct M2 MΦ subtypes and supports the concept of a continuum of macrophage activation states rather than two well-separated and functionally distinct M1/M2 MΦ classes, as originally proposed within a classical M1/M2 MΦ framework.