bluuebunny/crossref_metadata_2025 huggingface dataset:
Low–Harmonic Control Strategy of a Dual Three–Phase Synchronous Reluctance Motor Based on Three–Vector Synthesis
Authors: Huang Yonghong , Liu Yihang , Wang Qicuan , Yang Fan
Published: September 2022

Dual three–phase synchronous reluctance motors (DTP–SynRM) have the advantages of simple structure, high power density, fast dynamic response, and small torque ripple, and have broad application prospects in flywheel batteries. However, the synchronous reluctance motor has no permanent magnet, and the inductance value will change with the current change in actual operation. Direct torque control (DTC) is more suitable for the control strategy of dual three–phase synchronous reluctance motors because of its low dependence on motor parameters. However, traditional direct torque control uses a large vector control motor within one control period, which can not suppress the inherent 5th and 7th current harmonics in the motor. A new harmonic suppression method is proposed in this paper: that is, using a low harmonic vector to replace a large vector in traditional direct torque control, which can be synthesized by adjusting the action time and order of three adjacent large vectors within one control period. Through this improvement, torque control can have a harmonic suppression effect. The three vector synthesis method can make full use of the existing space voltage vector, and to adapt to different working conditions, two synthesis methods of switching frequency reduction and constant torque response are proposed. An improved direct torque control strategy is obtained by optimizing the design of the switch table using a new vector synthesis method. Finally, the suppression effect of traditional DTC and improved DTC on current harmonics is compared and analyzed. The results show that the direct torque control with low harmonic vector can suppress the harmonic current in x–y subspace, and the current harmonic content is greatly reduced.
Experimental Thermal Response Study of Multilayered, Encapsulated, PCM-Integrated Building Construction Materials
Authors: Rehman Atiq Ur , Sheikh Shakil R. , Kausar Zareena , Grimes Michael , McCormack Sarah J.
Published: September 2022

Thermal energy storage integration using phase change materials (PCMs) in buildings has great potential for energy conservation and greenhouse gas (GHG) emission reduction. Cutting-edge research and innovative ideas are required when using multilayered PCMs within typical construction materials to take advantage of their heat storage capability over a wide temperature range within buildings. This current study was carried out to experimentally test the efficacy of using dual PCMs RT28HC and RT21HC with different melting temperature ranges (28 °C and 21 °C) under variable thermal loading. The transient thermal response of various PCM-based configurations of concrete and cement blocks at different temperature inputs was obtained to determine the effectiveness of dual PCMs and their optimized configuration under experimental laboratory conditions. The range of the temperature input was varied from 22 °C to 50 °C, suitable for hot climatic conditions such as those in Pakistan. Laboratory ambient temperatures remained at ~17 °C for all experimental tests. Moreover, the results were compared using two parameters, i.e., decrement factor (DF) and time lag (TL). With DF and TL values of 0.10 and 5.72, respectively, in the high-temperature heating (HTH) regime and a low DF value of 0.08 and high TL of 5.17 in the moderate-temperature heating (MTH) regime, the RT28HC–RT21HC combination proved to be the most effective. The application of the RT28HC–RT21HC combination provided up to a 54.3% reduction in indoor temperatures in the HTH regime. This research contributes through experimental validation that these novel configurations are capable of providing substantial improvement in indoor thermal comfort.
Joint History Matching of Multiple Types of Field Data in a 3D Field-Scale Case Study
Authors: Cruz William Chalub , Luo Xiaodong , Petvipusit Kurt Rachares
Published: September 2022

This work presents an ensemble-based workflow to simultaneously assimilate multiple types of field data in a proper and consistent manner. The aim of using multiple field datasets is to improve the reliability of estimated reservoir models and avoid the underestimation of uncertainties. The proposed framework is based on an integrated history matching workflow, in which reservoir models are conditioned simultaneously on production, tracer and 4D seismic data with the help of three advanced techniques: adaptive localization (for better uncertainty quantification), weight adjustment (for balancing the influence of different types of field data), and sparse data representation (for handling big datasets). The integrated workflow is successfully implemented and tested in a 3D benchmark case with a set of comparison studies (with and without tracer data). The findings of this study indicate that joint history matching using production, tracer and 4D seismic data results in better estimated reservoir models and improved forecast performance. Moreover, the integrated workflow is flexible, and can be extended to incorporate more types of field data for further performance improvement. As such, the findings of this study can help to achieve a better understanding of the impacts of multiple datasets on history matching performance, and the proposed integrated workflow could serve as a useful tool for real field case studies in general.
Longitudinal Analysis of Sucralose at a Water Treatment Wetland
Authors: Young Nicholas , Welch Joseph , Hill Tyler , Sees Mark , Beazley Melanie , Heider Emily C.
Published: September 2022

Sales of low-calorie sweeteners are increasing in the Unites States, with sucralose representing the second largest of the U.S. market share. Since >99% of ingested sucralose is excreted as the parent compound, it represents a contaminant of emerging concern and has been proposed as an indicator of pollution of natural waters by anthropogenic waste. Many report that it is increasingly omnipresent in surface, coastal, and drinking water. Given the increasing consumption of low-calorie sweeteners, changes in influent and effluent sucralose concentrations presage their concentrations in natural waters. The aim of this research was to quantify sucralose at a constructed treatment wetland that was designed to remove nutrients (nitrogen and phosphorus) from secondary treated wastewater. We report the concentrations of sucralose in the surface water, sediment, and porewater throughout the flow train of the wetlands over a period of three years and include surface water sampling following an extreme weather event. The average influent surface water concentration of sucralose was 24 ± 2 ppb, and the average outfall concentration was 20 ± 6 ppb, indicating the sucralose is not subjected to chemical or physical adsorption in the sediment within the wetland.
What Makes Wildfires Destructive in California?
Authors: Syphard Alexandra D. , Keeley Jon E. , Gough Mike , Lazarz Mitchell , Rogan John
Published: September 2022

As human impacts from wildfires mount, there is a pressing need to understand why structures are lost in destructive fires. Despite growing research on factors contributing to structure loss, fewer studies have focused on why some fires are destructive and others are not. We characterized overall differences between fires that resulted in structure loss (“destructive fires”) and those that did not (“non-destructive wildfires”) across three California regions. Then, we performed statistical analyses on large fires only (≥100 ha) to distinguish the primary differences between large destructive large fires and large non-destructive fires. Overall, destructive fires were at least an order of magnitude larger than non-destructive fires, with the largest area burned varying by season in different regions. Fire severity was also significantly higher in destructive than non-destructive fires. The statistical analysis showed that, in the San Francisco Bay Area and the northern Sierra Nevada foothills, proximity to the Wildland Urban Interface (WUI) was by far the most important factor differentiating destructive and non-destructive wildfires, followed by different combinations of short-term weather, seasonal climate, topography, and vegetation productivity. In Southern California, wind velocity on the day of the fire ignition was the top factor, which is consistent with previous assumptions that wind-driven fires tend to be most destructive and most of the destruction occurs within the first 24 h. Additionally, Southern California’s high population density increases the odds that a human-caused wildfire may occur during a severe fire-weather event. The geographical differences among regions and the variation of factors explaining the differences between large destructive and large non-destructive fires reflects the complexity inherent in decision-making for reducing wildfire risk. Land use planning to reduce future exposure of housing development to fire and increased focus on wildfire ignition prevention emerge as two approaches with substantial potential.
Allometry and Individual Growth of the Temperate Pacific Sardine (Sardinops sagax) Stock in the Southern California Current System
Authors: Enciso-Enciso Concepción , Nevárez-Martínez Manuel Otilio , Sánchez-Cárdenas Rebeca , Marín-Enríquez Emigdio , Salcido-Guevara Luis A. , Minte-Vera Carolina
Published: September 2022

We analyzed individual growth and body mass allometry of the temperate stock of Sardinops sagax from samples collected on commercial fleet during 2005 to 2014 in the southern California Current System. Ages were estimated on otolith growth ring reading. Age (years) and standard length (SL; mm) data were fitted using four growth models: von Bertalanffy (VBM), Gompertz (GM), logistic (LM), and Schnute (SM) models. Parameters of each model were calculated by the maximum likelihood method using Akaike information criterion and Akaike’s weight (WAICi) to select the model with the greatest plausibility. Additionally, the interannual growth performance (φ′) variation was described. Body mass allometry was established from the relationship between total body mass (TM; g) and standard length. The sardine samples ranged in size from 114 to 226 mm SL and in weight from 20 to 192 g TM; ages varied from 0.5 to 6.0 years. The allometric parameter (b) was estimated to be 3.155 (3.154–3.156), showing a hyper-allometry growth type. On the basis of raw data, we found that the LM model fit the original data better (WAICi ~35%). When models were fitted to data bolstered with simulated values, the VBM model obtained the greatest weight (WAICi = 60.9%), but the LM model had null plausibility. Consequently, we determined that the Pacific sardine growth pattern was best described by the VBM model, which appears to be more robust against biased data. The φ′ showed interannual variation (2.13–2.51), with an average of φ′ = 2.25. An apparent inverse relationship was observed between φ′ and the Oceanic Niño Index (ONI) or the Pacific Decadal Oscillation (PDO) and the apparent positive relationship between Upwelling Index (UI) and φ’.
Some New Inequalities and Extremal Solutions of a Caputo–Fabrizio Fractional Bagley–Torvik Differential Equation
Authors: Xu Haiyong , Zhang Lihong , Wang Guotao
Published: September 2022

This paper studies the existence of extremal solutions for a nonlinear boundary value problem of Bagley–Torvik differential equations involving the Caputo–Fabrizio-type fractional differential operator with a non-singular kernel. With the help of a new inequality with a Caputo–Fabrizio fractional differential operator, the main result is obtained by applying a monotone iterative technique coupled with upper and lower solutions. This paper concludes with an illustrative example.
A New Approach Using Integral Transform to Solve Cancer Models
Authors: Saadeh Rania , Qazza Ahmad , Amawi Kawther
Published: September 2022

The objective of this work is to investigate analytical solutions of some models of cancer tumors using the Laplace residual power series method (LRPSM). The proposed method was effective and required simple calculations to find the analytic series solution, utilizing computer software such as the Mathematica package. Figures and graphs of the attained analytical Maclaurin solutions are presented to depict the procedure. The outcomes we obtained in this research showed the applicability and strength of the proposed approach in studying numerical series solutions of differential equations of fractional orders.
The Charge and Phase State of Liposomes Dramatically Affects the Binding of Mannosylated Chitosan
Authors: Le-Deygen Irina M. , Rokosovina Viktoria V. , Skuredina Anna A. , Yakimov Ivan D. , Kudryashova Elena V.
Published: September 2022

Liposomal complexes with mucoadhesive polymers, e.g., mannosylated chitosan, are considered as prospective antituberculosis drug delivery systems. The properties of such complexes can be critically affected by the charge and phase state of liposomes. The aim of our work was to study the interaction of mannosylated chitosan with liposomes of various compositions and to identify the key patterns of this process. We tracked the interaction by titrating the liposomes with an increasing base-molar excess using the DLS method and ATR-FTIR spectroscopy. Sorption isotherms were obtained using ATR-FTIR spectroscopy and linearized in the Scatchard coordinates to evaluate the dissociation constant (Kdis). The inclusion of cardiolipin (CL) in the lipid composition helps to reduce the Kdis of the complexes by an order of magnitude of 3.8 × 10−4 M and 6.4 × 10−5 M for dipalmitoylphosphatidylcholine (DPPC) and DPPC:CL 80:20 (weight ratio), respectively. Preheating at 37 °C of gel-like anionic liposomes helps to reduce the Kdis to 3.5 × 10−5 M. Anionic liposomes, both in liquid crystal and in the gel-like state, form multipoint non-covalent complexes with chitosan–mannose conjugates due to the partial neutralization of the charges on the surface of the vesicles. Meanwhile, neutral liposomes in both states form unstable heterogeneous complexes, probably due to the predominant sorption of the polymer on the vesicles. Complex formation provides preferable binding with the model mannose-binding receptor concanavalin A and sustained pH-sensitive release of the antituberculosis drug moxifloxacin.
Comparing Root Cohesion Estimates from Three Models at a Shallow Landslide in the Oregon Coast Range
Authors: Cronkite-Ratcliff Collin , Schmidt Kevin M. , Wirion Charlotte
Published: September 2022

Although accurate root cohesion model estimates are essential to quantify the effect of vegetation roots on shallow slope stability, few means exist to independently validate such model outputs. One validation approach for cohesion estimates is back-calculation of apparent root cohesion at a landslide site with well-documented failure conditions. The catchment named CB1, near Coos Bay, Oregon, USA, which experienced a shallow landslide in 1996, is a prime locality for cohesion model validation, as an abundance of data and observations from the site generated broad insights related to hillslope hydrology and slope stability. However, previously published root cohesion values at CB1 used the Wu and Waldron model (WWM), which assumes simultaneous root failure and therefore likely overestimates root cohesion. Reassessing published cohesion estimates from this site is warranted, as more recently developed models include the fiber bundle model (FBM), which simulates progressive failure with load redistribution, and the root bundle model-Weibull (RBMw), which accounts for differential strain loading. We applied the WWM, FBM, and RBMw at CB1 using post-failure root data from five vegetation species. At CB1, the FBM and RBMw predict values that are less than 30% of the WWM-estimated values. All three models show that root cohesion has substantial spatial heterogeneity. Most parts of the landslide scarp have little root cohesion, with areas of high cohesion concentrated near plant roots. These findings underscore the importance of using physically realistic models and considering lateral and vertical spatial heterogeneity of root cohesion in shallow landslide initiation and provide a necessary step towards independently assessing root cohesion model validity.
Effect of COVID-19-Induced Stress among Males on the Partner Relationship and Sexual Activity during COVID-19 Pandemic: A Cross-Sectional Study
Authors: Alzahrani Meshari A. , Alkhamees Mohammad , Almutairi Sulaiman , Abumelha Saad M. , Khan Muhammad Anwar , AL-Jaziri Zainab Y. , Althunayyan Fay A. , Hakami Basel O. , Ahmad Mohammad Shakil
Published: September 2022

Introduction: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there have been some reports regarding the impact of COVID-19 on male psychosexual health. Aims and Objectives: To assess the severity of stress during COVID-19 and to determine the association of stress levels with partner relationships and sexual activity. Methodology: A cross-sectional study was conducted in Saudi Arabia through social media platforms via an online questionnaire between 1 December 2020 and 31 January 2021 among 871 participants after a pilot study among 20 participants, of which 497 were included in the study. Stress levels were assessed using the Arabic version of the Depression, Anxiety, and Stress Scale (DASS-21). Statistical analysis was conducted using SPSS version 20.0. Responses were presented as frequencies and percentages, and associations were studied using the Chi-squared test/Fisher’s exact test. A value of p ≤ 0.05 was considered significant. Results: A total of 497 participants who had been infected with COVID-19 completed the survey. In total, it was found that 203 (40.8%) had severe stress scores (severe and extremely severe scores merged), while 131 (26.4%) had moderate stress scores. About 84 (16.9%) participants agreed that their sexual desire decreased, 91 (18.1%) confirmed their sexual intercourse frequency decreased, and sexual satisfaction decreased in 76 (15.3%). A significant positive correlation was found in that those who disagreed with having a good sexual relationship tended to have severe stress (p < 0.001). Conclusion: There were increased levels of stress during the lockdown period, which impacted psychosexual health.
Air-Pruning Containers Modify Root and Scion Growth and Alter Resource Allocation of Bench-Grafted Apple Plants
Authors: Elsysy Mokhles , Einhorn Todd C.
Published: September 2022

The profitability of modern apple orchard plantings depends largely on how rapidly the costs of planting are returned. Tree establishment and growth in the formative years are often can be limited by transplant shock associated with bare-root trees. In this experiment, we examined the effect of two planting systems, air-pruning containers, and field-grown liners, on above- and below-ground growth and development during the first year in the nursery. M9 ‘Nic 29’ bench grafts for three apple cultivars of different vigor classes, ‘Fuji’ (high vigor), ‘Gala’ (moderate vigor), and ‘Honeycrisp’ (low vigor). We hypothesized that air root-pruning containers would alter rooting distribution compared to field-grown liners by increasing fine root production, and this, in turn, would result in improved resource allocation and greater biomass partitioned to above-ground organs. Bench grafts were divided evenly between a field-grown liner bed (for bare root production) and an air-pruning container system. Air-pruning containers produced trees with significantly more root tips and greater total root length per tree than field-grown liners. Importantly, air-pruning containers resulted in a marked and significant increase in roots < 0.4 mm in diameter; however, field-grown liners produced trees had significantly more roots with diameters > 1.5 mm and, thus, significantly greater root dry matter content (DMC). Above-ground parameters (scion length, DMC of wood and leaves, and individual leaf area and DMC) were significantly increased for plants in air-pruning containers. Generally, the growth benefits from air-pruning containers were less pronounced in ‘Gala’ compared to ‘Honeycrisp’ or ‘Fuji’. The percentage of total DMC partitioned to the canopies of air-pruning containerized trees was significantly greater than field-grown liners.
Novel Targets for a Combination of Mechanical Unloading with Pharmacotherapy in Advanced Heart Failure
Authors: Jedrzejewska Agata , Braczko Alicja , Kawecka Ada , Hellmann Marcin , Siondalski Piotr , Slominska Ewa , Kutryb-Zajac Barbara , Yacoub Magdi H. , Smolenski Ryszard T.
Published: September 2022

LVAD therapy is an effective rescue in acute and especially chronic cardiac failure. In several scenarios, it provides a platform for regeneration and sustained myocardial recovery. While unloading seems to be a key element, pharmacotherapy may provide powerful tools to enhance effective cardiac regeneration. The synergy between LVAD support and medical agents may ensure satisfying outcomes on cardiomyocyte recovery followed by improved quality and quantity of patient life. This review summarizes the previous and contemporary strategies for combining LVAD with pharmacotherapy and proposes new therapeutic targets. Regulation of metabolic pathways, enhancing mitochondrial biogenesis and function, immunomodulating treatment, and stem-cell therapies represent therapeutic areas that require further experimental and clinical studies on their effectiveness in combination with mechanical unloading.
A Novel Pathway of Chlorimuron-Ethyl Biodegradation by Chenggangzhangella methanolivorans Strain CHL1 and Its Molecular Mechanisms
Authors: Yu Zhixiong , Dai Yumeng , Li Tingting , Gu Wu , Yang Yi , Li Xiang , Peng Pai , Yang Lijie , Li Xinyu , Wang Jian , Su Zhencheng , Li Xu , Xu Mingkai , Zhang Huiwen
Published: September 2022

Chlorimuron-ethyl is a widely used herbicide in agriculture. However, uncontrolled chlorimuron-ethyl application causes serious environmental problems. Chlorimuron-ethyl can be effectively degraded by microbes, but the underlying molecular mechanisms are not fully understood. In this study, we identified the possible pathways and key genes involved in chlorimuron-ethyl degradation by the Chenggangzhangella methanolivorans strain CHL1, a Methylocystaceae strain with the ability to degrade sulfonylurea herbicides. Using a metabolomics method, eight intermediate degradation products were identified, and three pathways, including a novel pyrimidine-ring-opening pathway, were found to be involved in chlorimuron-ethyl degradation by strain CHL1. Transcriptome sequencing indicated that three genes (atzF, atzD, and cysJ) are involved in chlorimuron-ethyl degradation by strain CHL1. The gene knock-out and complementation techniques allowed for the functions of the three genes to be identified, and the enzymes involved in the different steps of chlorimuron-ethyl degradation pathways were preliminary predicted. The results reveal a previously unreported pathway and the key genes of chlorimuron-ethyl degradation by strain CHL1, which have implications for attempts to enrich the biodegradation mechanism of sulfonylurea herbicides and to construct engineered bacteria in order to remove sulfonylurea herbicide residues from environmental media.
Apolipoprotein E in Cardiometabolic and Neurological Health and Diseases
Authors: Alagarsamy Jeyashree , Jaeschke Anja , Hui David Y.
Published: September 2022

A preponderance of evidence obtained from genetically modified mice and human population studies reveals the association of apolipoprotein E (apoE) deficiency and polymorphisms with pathogenesis of numerous chronic diseases, including atherosclerosis, obesity/diabetes, and Alzheimer’s disease. The human APOE gene is polymorphic with three major alleles, ε2, ε3 and ε4, encoding apoE2, apoE3, and apoE4, respectively. The APOE gene is expressed in many cell types, including hepatocytes, adipocytes, immune cells of the myeloid lineage, vascular smooth muscle cells, and in the brain. ApoE is present in subclasses of plasma lipoproteins, and it mediates the clearance of atherogenic lipoproteins from plasma circulation via its interaction with LDL receptor family proteins and heparan sulfate proteoglycans. Extracellular apoE also interacts with cell surface receptors and confers signaling events for cell regulation, while apoE expressed endogenously in various cell types regulates cell functions via autocrine and paracrine mechanisms. This review article focuses on lipoprotein transport-dependent and -independent mechanisms by which apoE deficiency or polymorphisms contribute to cardiovascular disease, metabolic disease, and neurological disorders.
11C-Methionine PET/CT in Assessment of Multiple Myeloma Patients: Comparison to 18F-FDG PET/CT and Prognostic Value
Authors: Morales-Lozano Maria I. , Rodriguez-Otero Paula , Sancho Lidia , Nuñez-Cordoba Jorge M. , Prieto Elena , Marcos-Jubilar Maria , Rosales Juan J. , Alfonso Ana , Guillen Edgar F. , San-Miguel Jesus , Garcia-Velloso Maria J.
Published: September 2022

Multiple myeloma (MM) is the second most common haematological malignancy and remains incurable despite therapeutic advances. 18F-FDG (FDG) PET/CT is a relevant tool MM for staging and it is the reference imaging technique for treatment evaluation. However, it has limitations, and investigation of other PET tracers is required. Preliminary results with L-methyl-[11C]- methionine (MET), suggest higher sensitivity than 18F-FDG. This study aimed to compare the diagnostic accuracy and prognostic value of 1FDG and MET in MM patients. We prospectively compared FDG and MET PET/CT for assessment of bone disease and extramedullary disease (EMD) in a series of 52 consecutive patients (8 smoldering MM, 18 newly diagnosed MM and 26 relapsed MM patients). Bone marrow (BM) uptake patterns and the detection of focal lesions (FLs) and EMD were compared. Furthermore, FDG PET parameters with known MM prognostic value were explored for both tracers, as well as total lesion MET uptake (TLMU). Median patient age was 61 years (range, 37–83 years), 54% were male, 13% of them were in stage ISS (International Staging System) III, and 31% had high-risk cytogenetics. FDG PET/CT did not detect active disease in 6 patients, while they were shown to be positive by MET PET/CT. Additionally, MET PET/CT identified a higher number of FLs than FDG in more than half of the patients (63%). For prognostication we focussed on the relapsed cohort, due to the low number of progressions in the two other cohorts. Upon using FDG PET/CT in relapsed patients, the presence of more than 3 FLs (HR 4.61, p = 0.056), more than 10 FLs (HR 5.65, p = 0.013), total metabolic tumor volume (TMTV) p50 (HR 4.91, p = 0.049) or TMTV p75 (HR 5.32, p = 0.016) were associated with adverse prognosis. In MET PET/CT analysis, TMTV p50 (HR 4.71, p = 0.056), TMTV p75 (HR 6.27, p = 0.007), TLMU p50 (HR 8.8, p = 0.04) and TLMU p75 (HR 6.3, p = 0.007) adversely affected PFS. This study confirmed the diagnostic and prognostic value of FDG in MM. In addition, it highlights that MET has higher sensitivity than FDG PET/CT for detection of myeloma lesions, including FLs. Moreover, we show, for the first time, the prognostic value of TMTV and TLMU MET PET/CT in the imaging evaluation of MM patients.
Embryonic Exposure to Cigarette Smoke Extract Impedes Skeletal Development and Evokes Craniofacial Defects in Zebrafish
Authors: Karmach Omran , Madrid Joseph V. , Dasgupta Subham , Volz David C. , zur Nieden Nicole I.
Published: September 2022

Exposure to cigarette smoke represents the largest source of preventable death and disease in the United States. This may be in part due to the nature of the delayed harmful effects as well as the lack of awareness of the scope of harm presented by these products. The presence of “light” versions further clouds the harmful effects of tobacco products. While active smoking in expectant mothers may be reduced by educational and outreach campaigns, exposure to secondhand smoke is often involuntary yet may harm the developing embryo. In this study, we show that the main component of secondhand smoke, sidestream cigarette smoke, from several brands, including harm-reduction versions, triggered unsuccessful hatching at 3 dpf and reduced overall survival at 6 dpf in developing zebrafish. At non-lethal concentrations, craniofacial defects with different severity based on the cigarette smoke extract were noted by 6 dpf. All tested products, including harm-reduction products, significantly impacted cartilage formation and/or bone mineralization in zebrafish embryos, independent of whether the bones/cartilage formed from the mesoderm or neural crest. Together, these results in a model system often used to detect embryonic malformations imply that exposure of a woman to secondhand smoke while pregnant may lead to mineralization issues in the skeleton of her newborn, ultimately adding a direct in utero association to the increased fracture risk observed in children of mothers exposed to cigarette smoke.
Unbalanced Expression of Glutathione Peroxidase 4 and Arachidonate 15-Lipoxygenase Affects Acrosome Reaction and In Vitro Fertilization
Authors: Soria-Tiedemann Mariana , Michel Geert , Urban Iris , Aldrovandi Maceler , O’Donnell Valerie , Stehling Sabine , Kuhn Hartmut , Borchert Astrid
Published: September 2022

Glutathione peroxidase 4 (Gpx4) and arachidonic acid 15 lipoxygenase (Alox15) are counterplayers in oxidative lipid metabolism and both enzymes have been implicated in spermatogenesis. However, the roles of the two proteins in acrosomal exocytosis have not been explored in detail. Here we characterized Gpx4 distribution in mouse sperm and detected the enzyme not only in the midpiece of the resting sperm but also at the anterior region of the head, where the acrosome is localized. During sperm capacitation, Gpx4 translocated to the post-acrosomal compartment. Sperm from Gpx4+/Sec46Ala mice heterozygously expressing a catalytically silent enzyme displayed an increased expression of phosphotyrosyl proteins, impaired acrosomal exocytosis after in vitro capacitation and were not suitable for in vitro fertilization. Alox15-deficient sperm showed normal acrosome reactions but when crossed into a Gpx4-deficient background spontaneous acrosomal exocytosis was observed during capacitation and these cells were even less suitable for in vitro fertilization. Taken together, our data indicate that heterozygous expression of a catalytically silent Gpx4 variant impairs acrosomal exocytosis and in vitro fertilization. Alox15 deficiency hardly impacted the acrosome reaction but when crossed into the Gpx4-deficient background spontaneous acrosomal exocytosis was induced. The detailed molecular mechanisms for the observed effects may be related to the compromised redox homeostasis.
Mechano-Sensing Channel PIEZO2 Enhances Invasive Phenotype in Triple-Negative Breast Cancer
Authors: Katsuta Eriko , Takabe Kazuaki , Vujcic Marija , Gottlieb Philip A. , Dai Tao , Mercado-Perez Arnaldo , Beyder Arthur , Wang Qingfei , Opyrchal Mateusz
Published: September 2022

Background: Mechanically gated PIEZO channels lead to an influx of cations, activation of additional Ca2+ channels, and cell depolarization. This study aimed to investigate PIEZO2’s role in breast cancer. Methods: The clinical relevance of PIEZO2 expression in breast cancer patient was analyzed in a publicly available dataset. Utilizing PIEZO2 overexpressed breast cancer cells, and in vitro and in vivo experiments were conducted. Results: High expression of PIEZO2 was correlated with a worse survival in triple-negative breast cancer (TNBC) but not in other subtypes. Increased PEIZO2 channel function was confirmed in PIEZO2 overexpressed cells after mechanical stimulation. PIEZO2 overexpressed cells showed increased motility and invasive phenotypes as well as higher expression of SNAIL and Vimentin and lower expression of E-cadherin in TNBC cells. Correspondingly, high expression of PIEZO2 was correlated with the increased expression of epithelial–mesenchymal transition (EMT)-related genes in a TNBC patient. Activated Akt signaling was observed in PIEZO2 overexpressed TNBC cells. PIEZO2 overexpressed MDA-MB-231 cells formed a significantly higher number of lung metastases after orthotopic implantation. Conclusion: PIEZO2 activation led to enhanced SNAIL stabilization through Akt activation. It enhanced Vimentin and repressed E-cadherin transcription, resulting in increased metastatic potential and poor clinical outcomes in TNBC patients.
Quantitative Plasma Proteomics to Identify Candidate Biomarkers of Relapse in Pediatric/Adolescent Hodgkin Lymphoma
Authors: Repetto Ombretta , Caggiari Laura , De Zorzi Mariangela , Elia Caterina , Mussolin Lara , Buffardi Salvatore , Pillon Marta , Muggeo Paola , Casini Tommaso , Steffan Agostino , Mauz-Körholz Christine , Mascarin Maurizio , De Re Valli
Published: September 2022

Classical pediatric Hodgkin Lymphoma (HL) is a rare malignancy. Therapeutic regimens for its management may be optimized by establishing treatment response early on. The aim of this study was to identify plasma protein biomarkers enabling the prediction of relapse in pediatric/adolescent HL patients treated under the pediatric EuroNet-PHL-C2 trial. We used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics at the time of diagnosis—before any therapy—as semiquantitative method to profile plasma proteins specifically associated with relapse in 42 children with nodular sclerosing HL. In both the exploratory and the validation cohorts, six proteins (apolipoprotein E, C4b-binding protein α chain, clusterin, fibrinogen γ chain, prothrombin, and vitronectin) were more abundant in the plasma of patients whose HL relapsed (|fold change| ≥ 1.2, p < 0.05, Student’s t-test). Predicting protein function with the Gene Ontology classification model, the proteins were included in four biological processes (p < 0.01). Using immunoblotting and Luminex assays, we validated two of these candidate biomarkers—C4b-binding protein α chain and clusterin—linked to innate immune response function (GO:0045087). This study identified C4b-binding protein α chain and clusterin as candidate early plasma biomarkers of HL relapse, and important for the purpose of shedding light on the molecular scenario associated with immune response in patients treated under the EuroNet-PHL-C2 trial.
All-trans Retinoic Acids Synergistically and Beneficially Affect In Vitro Glaucomatous Trabecular Meshwork (TM) Models Using 2D and 3D Cell Cultures of Human TM Cells
Authors: Watanabe Megumi , Sato Tatsuya , Tsugeno Yuri , Higashide Megumi , Furuhashi Masato , Umetsu Araya , Suzuki Soma , Ida Yosuke , Hikage Fumihito , Ohguro Hiroshi
Published: September 2022

We report herein on the effects of all-trans retinoic acid (ATRA) on two-dimensional (2D) and three-dimensional (3D) cultures of human trabecular meshwork (HTM) cells that were treated with transforming growth factor β2 (TGF-β2). In the presence of 5 ng/mL TGF-β2, the effects of ATRA on the following were observed: (1) the barrier function of the 2D HTM monolayers, as determined by trans-endothelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) dextran permeability measurements; (2) a Seahorse cellular bio-metabolism analysis; (3) physical properties, including the size and stiffness, of 3D spheroids; (4) the gene expression of extracellular matrix (ECM) molecules, ECM modulators including tissue inhibitor of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs), tight junction (TJ)-related molecules, and endoplasmic reticulum (ER)-stress-related factors. ATRA significantly inhibited the TGF-β2-induced increase in the TEER values and FITC dextran permeability of the 2D monolayers, while an ATRA monotreatment induced similar effects as TGF-β2. A real-time metabolic analysis revealed that ATRA significantly inhibited the TGF-β2-induced shift in metabolic reserve from mitochondrial oxidative phosphorylation to glycolysis in 2D HTM cells, whereas ATRA alone did not induce significant metabolic changes. In contrast, ATRA induced the formation of substantially downsized and softer 3D spheroids in the absence and presence of TGF-β2. The different effects induced by ATRA toward 2D and 3D HTM cells were also supported by the qPCR analysis of several proteins as above. The findings reported here indicate that ATRA may induce synergistic and beneficial effects on TGF-β2-treated 2D- and 3D-cultured HTM cells; those effects varied significantly between the 2D and 3D cultures.
Viral Infection and Airway Epithelial Immunity in Asthma
Authors: Kim So Ri
Published: September 2022

Viral respiratory tract infections are associated with asthma development and exacerbation in children and adults. In the course of immune responses to viruses, airway epithelial cells are the initial platform of innate immunity against viral invasion. Patients with severe asthma are more vulnerable than those with mild to moderate asthma to viral infections. Furthermore, in most cases, asthmatic patients tend to produce lower levels of antiviral cytokines than healthy subjects, such as interferons produced from immune effector cells and airway epithelial cells. The epithelial inflammasome appears to contribute to asthma exacerbation through overactivation, leading to self-damage, despite its naturally protective role against infectious pathogens. Given the mixed and complex immune responses in viral-infection-induced asthma exacerbation, this review examines the diverse roles of airway epithelial immunity and related potential therapeutic targets and discusses the mechanisms underlying the heterogeneous manifestations of asthma exacerbations.
Topical Administration of a Marine Oil Rich in Pro-Resolving Lipid Mediators Accelerates Wound Healing in Diabetic db/db Mice through Angiogenesis and Macrophage Polarization
Authors: Ontoria-Oviedo Imelda , Amaro-Prellezo Elena , Castellano Delia , Venegas-Venegas Elena , González-Santos Fernando , Ruiz-Saurí Amparo , Pelacho Beatriz , Prósper Felipe , Pérez del Caz María Dolores , Sepúlveda Pilar
Published: September 2022

Impaired wound healing in patients with type 2 diabetes (DM2) is characterized by chronic inflammation, which delays wound closure. Specialized pro-resolving lipid mediators (SPMs) are bioactive molecules produced from essential polyunsaturated fatty acids (PUFAs), principally omega-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). SPMs are potent regulators of inflammation and have been used to suppress chronic inflammation in peripheral artery disease, non-alcoholic fatty liver disease, and central nervous system syndromes. LIPINOVA® is a commercially available safe-grade nutritional supplement made from a fractionated marine lipid concentrate derived from anchovy and sardine oil that is rich in SPMs and EPA, as well as DHA precursors. Here, we assessed the effect of LIPINOVA® in wound dressing applications. LIPINOVA® showed biocompatibility with keratinocytes and fibroblasts, reduced the abundance of pro-inflammatory macrophages (Mφ1), and promoted in vitro wound closure. Daily application of the marine oil to open wounds made by punch biopsy in db/db mice promoted wound closure by accelerating the resolution of inflammation, inducing neoangiogenesis and Mφ1/Mφ2 macrophage polarization. In conclusion, LIPINOVA® displays pro-resolutive properties and could be exploited as a therapeutic agent for the treatment of diabetic ulcers.
Dioscorea nipponica Makino Rhizome Extract and Its Active Compound Dioscin Protect against Neuroinflammation and Scopolamine-Induced Memory Deficits
Authors: Azam Shofiul , Kim Yon-Suk , Jakaria Md. , Yu Ye-Ji , Ahn Jae-Yong , Kim In-Su , Choi Dong-Kug
Published: September 2022

Activation of microglial cells by intrinsic or extrinsic insult causes neuroinflammation, a common phenomenon in neurodegenerative diseases. Prevention of neuroinflammation may ameliorate many neurodegenerative disease progressions. Dioscorea nipponica Makino (DN) extract can alleviate muscular atrophy and inflammatory diseases; however, the efficacy and mechanism of action in microglial cells remain unknown. The current study investigates the possible anti-inflammatory effects and mechanisms of Dioscorea nipponica Makino ethanol extract and its steroidal saponin dioscin. Our in vitro study shows that Dioscorea nipponica rhizome ethanol extract (DNRE) and dioscin protect against lipopolysaccharide (LPS)-activated inflammatory responses in BV-2 microglial cells by inhibiting phosphorylation and the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), resulting in the downregulation of pro-inflammatory cytokines and enzymes. Consistent with our previous report of dioscin-mediated enhancement of neurotrophic factors in dopaminergic cells, here we found that dioscin upregulates brain-derived neurotrophic factor (BDNF) and cAMP-response element binding protein (CREB) phosphorylation (pCREB) in the cerebral cortex and hippocampus regions of the mouse brain. Scopolamine treatment increased pro-inflammatory enzyme levels and reduced the expression of BDNF and pCREB in the hippocampus and cortex regions, which led to impaired learning and referencing memory in mice. Pre-treatment of dioscin for 7 days substantially enhanced mice performances in maze studies, indicating amelioration in cognitive deficits. In conclusion, DNRE and its active compound dioscin protect against neurotoxicity most likely by suppressing NF-κB phosphorylation and upregulating neurotrophic factor BDNF.
Peppers in Diet: Genome-Wide Transcriptome and Metabolome Changes in Drosophila melanogaster
Authors: Lopez-Ortiz Carlos , Edwards Mary , Natarajan Purushothaman , Pacheco-Valenciana Armando , Nimmakayala Padma , Adjeroh Donald A. , Sirbu Cristian , Reddy Umesh K.
Published: September 2022

The habanero pepper (Capsicum chinense) is an increasingly important spice and vegetable crop worldwide because of its high capsaicin content and pungent flavor. Diets supplemented with the phytochemicals found in habanero peppers might cause shifts in an organism’s metabolism and gene expression. Thus, understanding how these interactions occur can reveal the potential health effects associated with such changes. We performed transcriptomic and metabolomic analyses of Drosophila melanogaster adult flies reared on a habanero pepper diet. We found 539 genes/59 metabolites that were differentially expressed/accumulated in flies fed a pepper versus control diet. Transcriptome results indicated that olfactory sensitivity and behavioral responses to the pepper diet were mediated by olfactory and nutrient-related genes including gustatory receptors (Gr63a, Gr66a, and Gr89a), odorant receptors (Or23a, Or59a, Or82a, and Orco), and odorant-binding proteins (Obp28a, Obp83a, Obp83b, Obp93a, and Obp99a). Metabolome analysis revealed that campesterol, sitosterol, and sucrose were highly upregulated and azelaic acid, ethyl phosphoric acid, and citric acid were the major metabolites downregulated in response to the habanero pepper diet. Further investigation by integration analysis between transcriptome and metabolome data at gene pathway levels revealed six unique enriched pathways, including phenylalanine metabolism; insect hormone biosynthesis; pyrimidine metabolism; glyoxylate, and dicarboxylate metabolism; glycine, serine, threonine metabolism; and glycerolipid metabolism. In view of the transcriptome and metabolome findings, our comprehensive analysis of the response to a pepper diet in Drosophila have implications for exploring the molecular mechanism of pepper consumption.
Effect of COVID-19 Pandemic on Medical Students—A Single Center Study
Authors: Poluch Maria , Ries Robert , Ahmed Monjur
Published: September 2022

Background: The COVID-19 pandemic caused medical education to shift unprecedentedly, leading medical schools to switch to virtual platforms and modify student-patient interactions. On top of educational changes, medical students adapted to their support network, finances, and mental and physical health changes. Objective: To understand the holistic impact of COVID-19 on medical students and medical education and identify how to distribute resources during future educational disruptions in a large medical university in the United States. Methods: An anonymous online survey was distributed to medical students at Sidney Kimmel Medical College, Philadelphia, in February 2021. Participants self-reported the impact of the COVID-19 pandemic on their medical education, family life, financial burden, mental health, and physical health. Results: 168 out of 1088 students at Sidney Kimmel Medical College completed the survey, with 58% (98/168) of the respondents identifying as female. The class breakdown was as follows: 38% (63/168) first years, 18% (31/168) second years, 21% (36/168) third years, 20% (34/168) fourth years, and 2% (4/168) were considered “other” (including research year, Master’s program). A total of 28% of respondents reported developing new mental illness, with second years having the highest incidence at 39%. In total, 42% said the pandemic affected a previous mental health condition. Further, 96% of third and fourth years reported COVID-19 affected their clinical rotations. In total, 68% of first years reported their entrance to medical school was severely affected. Moreover, 13% reported losing a family member due to COVID-19, and 7% reported personal sickness due to COVID-19. Additionally, 16% reported incurring a financial burden due to the pandemic. Conclusion: COVID-19 impacted the well-being of students by affecting their mental health and financial burdens. Clinical rotations and medical school entrance were the most problematic aspects. In the future setting of major educational disruptions, this study provides a starting point for where to focus resources, mental health support, financial support, and academic flexibility.
N-O Ligand Supported Stannylenes: Preparation, Crystal, and Molecular Structures
Authors: Sullivan Hannah S. I. , Straiton Andrew J. , Kociok-Köhn Gabriele , Johnson Andrew L.
Published: September 2022

A new series of tin(II) complexes (1, 2, 4, and 5) were successfully synthesized by employing hydroxy functionalized pyridine ligands, specifically 2-hydroxypyridine (hpH), 8-hydroxyquinoline (hqH), and 10-hydroxybenzo[h]quinoline (hbqH) as stabilizing ligands. Complexes [Sn(μ-κ2ON-OC5H4N)(N{SiMe3}2)]2 (1) and [Sn4(μ-κ2ON-OC5H4N)6(κ1O-OC5H4N)2] (2) are the first structurally characterized examples of tin(II) oxypyridinato complexes exhibiting {Sn2(OCN)2} heterocyclic cores. As part of our study, 1H DOSY NMR experiments were undertaken using an external calibration curve (ECC) approach, with temperature-independent normalized diffusion coefficients, to determine the nature of oligomerisation of 2 in solution. An experimentally determined diffusion coefficient (298 K) of 6.87 × 10−10 m2 s−1 corresponds to a hydrodynamic radius of Ca. 4.95 Å. This is consistent with the observation of an averaged hydrodynamic radii and equilibria between dimeric [Sn{hp}2]2 and tetrameric [Sn{hp}2]4 species at 298 K. Testing this hypothesis, 1H DOSY NMR experiments were undertaken at regular intervals between 298 K–348 K and show a clear change in the calculated hydrodynamic radii form 4.95 Å (298 K) to 4.35 Å (348 K) consistent with a tetramer ⇄ dimer equilibria which lies towards the dimeric species at higher temperatures. Using these data, thermodynamic parameters for the equilibrium (ΔH° = 70.4 (±9.22) kJ mol−1, ΔS° = 259 (±29.5) J K−1 mol−1 and ΔG°298 = −6.97 (±12.7) kJ mol−1) were calculated. In the course of our studies, the Sn(II) oxo cluster, [Sn6(m3-O)6(OR)4:{Sn(II)(OR)2}2] (3) (R = C5H4N) was serendipitously isolated, and its molecular structure was determined by single-crystal X-ray diffraction analysis. However, attempts to characterise the complex by multinuclear NMR spectroscopy were thwarted by solubility issues, and attempts to synthesise 3 on a larger scale were unsuccessful. In contrast to the oligomeric structures observed for 1 and 2, single-crystal X-ray diffraction studies unambiguously establish the monomeric 4-coordinate solid-state structures of [Sn(κ2ON-OC9H6N)2)] (4) and [Sn(κ2ON-OC13H8N)2)] (5).