bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Cogging Torque Reduction of Direct-Drive Type Dual-Rotor Radial Flux Permanent Magnet Synchronous Motor for Electric Propulsion Aircraft
Authors: Li Haomin , Feng Minglu , Lei Li , Geng Yingsan , Wang Jianhua
Published: March 2024

The direct-drive type high-torque-density motor is one of the most promising solutions of electric propulsion for aircraft. The cogging torque of the direct-drive motor causes torque ripple, vibration, and noise, which seriously affect the stability and reliability of the electric propulsion system for aircraft. In this paper, a novel direct-drive type high-torque-density dual-rotor radial flux permanent magnet synchronous motor (DRPMSM) is proposed, and its cogging torque is weakened by permanent magnet shape design and pole-arc coefficient combination. An eccentric and chamfered permanent magnet shape is proposed, and the influence of eccentric distance and chamfer angle on cogging torque is clarified. Through the pole-arc coefficient combination design of the inner and outer rotors of the DRPMSM, the cogging torques of the inner and outer rotor are phase reversed, thus further reducing the total cogging torque of the DRPMSM. By employing the response surface method, a mathematical model is established for the cogging torque of the DRPMSM in relation to the pole-arc coefficients, chamfer angle, and eccentric distance of the permanent magnets. The parameters that minimize the cogging torque of the DRPMSM are obtained using a genetic algorithm. A prototype is manufactured according to the optimized parameters, and experimental results validate the correctness of the theoretical analysis and the effectiveness of the optimization design method.
Self-Supporting np-AlFeNiO Bifunctional Electrode Material for Electrochemical Water Splitting Prepared by Electrooxidation
Authors: Ma Zhihui , Xu Wence , Gao Zhonghui , Liang Yanqin , Jiang Hui , Li Zhaoyang , Cui Zhenduo , Zhang Huifang , Zhu Shengli
Published: March 2024

Hydrogen production through water splitting is a promising path to develop renewable green energy. Effective, stable, and low-cost catalysts are the key to water splitting. In the present work, a series of self-supporting nanoporous alloys are prepared by using a dealloying process followed by electrooxidation. Among them, the np-AlFeNiO-4s sample exhibits remarkable activity (10 mA cm−2 at 32 mV for the HER and 278 mV for the OER) and good long-term stability (100 h) in alkaline conditions for both the HER and the OER. It only requires 1.56 V to reach 10 mA cm−2 current density for total water splitting performance. The very short time of electrooxidation can significantly improve the HER performance. Electrooxidation makes the metal and metal oxide sites on the electrode surface effectively coupled, which greatly enhances the kinetic rate of the Volmer and Heyrovsky steps. Appropriate electrooxidation is a rapid and easy way to improve the activity of the electrocatalyst, which has a broad application prospect in electrochemical water splitting.
High-Performance Hydrogen-Fueled Internal Combustion Engines: Feasibility Study and Optimization via 1D-CFD Modeling
Authors: Misul Daniela A. , Scopelliti Alex , Baratta Mirko
Published: March 2024

Hydrogen-powered mobility is believed to be crucial in the future, as hydrogen constitutes a promising solution to make up for the non-programmable character of the renewable energy sources. In this context, the hydrogen-fueled internal combustion engine represents one of the suitable technical solutions for the future of sustainable mobility. As a matter of fact, hydrogen engines suffer from limitations in volumetric efficiency due to the very low density of the fuel. Consequently, hydrogen-fueled ICEs can reach sufficient torque and power density only if suitable supercharging solutions are developed. Moreover, gaseous-engine performance can be improved to a great extent if direct injection is applied. In this perspective, a remarkable know-how has been developed in the last two decades on NG engines, which can be successfully exploited in this context. The objective of this paper is twofold. In the first part, a feasibility study has been carried out with reference to a typical 2000cc SI engine by means of 1D simulations. This study was aimed at characterizing the performance on the full load curve with respect to a baseline PFI engine fueled by NG. In this phase, the turbocharging/supercharging device has not been included in the model in order to quantify the attainable benefits in the absence of any limitation coming from the turbocharger. In the second part of this paper, the conversion of a prototype 1400cc direct injection NG engine, running with stoichiometric mixture, to run on a lean hydrogen combustion mode has been investigated via 1D simulations. The matching between engine and turbocharger has been included in the model, and the effects of two different turbomatching choices have been presented and discussed.
An Efficient Workflow for Quality Control Marker Screening and Metabolite Discovery in Dietary Herbs by LC-Orbitrap-MS/MS and Chemometric Methods: A Case Study of Chrysanthemum Flowers
Authors: Yuan Hanwen , Xie Qingling , Liang Ling , Luo Jiangyi , Jiang Sai , Peng Caiyun , Wang Wei
Published: March 2024

LC-MS is widely utilized in identifying and tracing plant-derived food varieties but quality control markers screening and accurate identification remain challenging. The adulteration and confusion of Chrysanthemum flowers highlight the need for robust quality control markers. This study established an efficient workflow by integrating UHPLC-Orbitrap-MS/MS with Compound Discoverer and chemometrics. This workflow enabled the systematic screening of 21 markers from 10,540 molecular features, which effectively discriminated Chrysanthemum flowers of different species and cultivars. The workflow incorporated targeted and untargeted methods by employing diagnostic product ions, fragmentation patterns, mzCloud, mzVault, and in-house databases to identify 206 compounds in the flowers, including 17 screened markers. This approach improved identification accuracy by reducing false positives, eliminating in-source fragmentation interference, and incorporating partial verification utilizing our established compound bank. Practically, this workflow can be instrumental in quality control, geolocation determination, and varietal tracing of Chrysanthemum flowers, offering prospective use in other plant-derived foods.
Impact of Incorporating Shiitake Mushrooms (Lentinula edodes) on Microbial Community and Flavor Volatiles in Traditional Jiuqu
Authors: Geng Jingzhang , He Siqiao , Zhang Shanshan , Tian Honglei , Jin Wengang
Published: March 2024

Jiuqu is one of the important raw materials for brewing Chinese rice wine (Huangjiu), often known as the “bone of wine”. In this study, the microbial community and flavor substances of Jiuqu made with different amounts of shiitake mushroom (Lentinula edodes) were investigated through high-throughput sequencing technology and headspace gas chromatography–ion migration spectroscopy (HS-GC-IMS), using traditional wheat yeast as a control. The results showed that 1593 genera and 5507 species were identified among the four types of yeast, with Aspergillus and Paecilomyces being the most dominant microorganisms at the genus level. Carbohydrate, coenzyme, and amino acid metabolism may be the main metabolic processes of the dominant microorganisms in Jiuqu. In terms of flavor, a total of 79 volatile substance monomers and some dimers were detected from four types of Jiuqu raw materials, with the main substances being 12 aldehydes, 19 ketones, 13 alcohols, 19 esters, 4 olefins, 1 acid, 3 ethers, 4 furans, 1 pyrazine, 1 pyridine, 1 triethylamine, and 1 thiazole. The correlation results indicate that Aspergillus, Lactobacillus, and Vibrio correlate significantly with the volatile flavor compounds unique to shiitake mushrooms and also have a positive effect on alcohol, esters, and furans. These results could shed light on the selection of Lentinula edodes as a fermentation starter for Huangjiu in the Qinba Mountain area.
On the Solvability of a Singular Time Fractional Parabolic Equation with Non Classical Boundary Conditions
Authors: Alhazzani Eman , Mesloub Said , Gadain Hassan Eltayeb
Published: March 2024

This paper deals with a singular two dimensional initial boundary value problem for a Caputo time fractional parabolic equation supplemented by Neumann and non-local boundary conditions. The well posedness of the posed problem is demonstrated in a fractional weighted Sobolev space. The used method based on some functional analysis tools has been successfully showed its efficiency in proving the existence, uniqueness and continuous dependence of the solution upon the given data of the considered problem. More precisely, for proving the uniqueness of the solution of the posed problem, we established an energy inequality for the solution from which we deduce the uniqueness. For the existence, we proved that the range of the operator generated by the considered problem is dense.
Causal Associations of Glaucoma and Age-Related Macular Degeneration with Cataract: A Bidirectional Two-Sample Mendelian Randomisation Study
Authors: Seo Je Hyun , Lee Young
Published: March 2024

Common age-related eye disorders include glaucoma, cataract, and age-related macular degeneration (AMD); however, little is known about their relationship with age. This study investigated the potential causal relationship between glaucoma and AMD with cataract using genetic data from multi-ethnic populations. Single-nucleotide polymorphisms (SNPs) associated with exposure to cataract were selected as instrumental variables (IVs) from genome-wide association studies using meta-analysis data from BioBank Japan and UK Biobank. A bidirectional two-sample Mendelian randomisation (MR) study was conducted to assess the causal estimates using inverse variance weighted, MR-Egger, and MR pleiotropy residual sum and outlier tests. SNPs with (p < 5.0 × 10−8) were selected as IVs for cataract, primary open-angle glaucoma, and AMD. We found no causal effects of cataract on glaucoma or AMD (all p > 0.05). Furthermore, there were no causal effects of AMD on cataract (odds ratio [OR] = 1.02, p = 0.400). However, glaucoma had a substantial causal effect on cataract (OR = 1.14, p = 0.020). Our study found no evidence for a causal relationship of cataract on glaucoma or AMD and a casual effect of AMD on cataract. Nonetheless, glaucoma demonstrates a causal link with cataract formation, indicating the need for future investigations of age-related eye diseases.
Hypertension Medication and Medicare Beneficiaries: Prescription Drug Coverage Satisfaction and Medication Non-Adherence among Older Adults
Authors: Park Jeong-Hui , Kim Kiyoung , Medina Mar , Ng Boon Peng , Smith Matthew Lee , Edafetanure-Ibeh Okeoghene Marcel , Chang Jongwha
Published: March 2024

Hypertension is so prevalent and requires strict adherence to medications to prevent further disease or death, but there is no study examining factors related to prescription drug non-adherence among 65 years old and older. This study aims to assess the likelihood of medication nonadherence among patients based on factors such as age, race, and socioeconomic status, with the goal of identifying strategies to enhance medication adherence and mitigate associated health risks. Using the 2020 Medicare Current Beneficiary Survey Public Use File to represent nationwide Medicare beneficiaries (unweighted n = 3917, weighted n = 27,134,782), medication non-adherence was related to multiple independent variables (i.e., age, sex, race/ethnicity, socioeconomic status, comorbidities, insurance coverage, and satisfaction with insurance). Cross-tabulations and Wald chi-square tests were used to determine how much each variable was related to non-adherence. Multivariate logistic regression was used to examine the association between medication non-adherence and factors such as prescription drug coverage satisfaction and cost-reducing behavior. Specific trends in medication non-adherence emerged among beneficiaries. Non-adherence was higher in older adults aged 65- to 74-year-olds and those with more chronic conditions (OR = 2.24; 95% CI = 1.74–2.89). If patients were dissatisfied with the medications on the insurance formulary or struggled to find a pharmacy that accepted their medication coverage, they had worse adherence (OR = 2.63; 95% CI = 1.80–3.84). Formulary and coverage must be expanded to improve adherence to antihypertensive medications in Medicare beneficiaries. Older adults aged 65 to 74 years may be less adherent to their medications because they do not see the seriousness of the disease and could benefit from further counseling. Patients with limited activities of daily living and more comorbidities may struggle with complex treatment regimens and should use adherence assistance tools.
Remote Pilates Training Is Effective in Improving Physical Fitness in Healthy Women: A Randomized Controlled Study
Authors: Lazarowitz Zanzuri Carine , Hadas Dan , Hutzler Yeshayahu , Goral Aviva , Tsuk Sharon
Published: March 2024

Despite its positive impact on physical and mental well-being, adults may refrain from performing regular physical activity, due to inadequate time, accessibility, or funds. Yet remote platforms could overcome such obstacles and increase participation. This study evaluated the effectiveness of remote-synchronous group-Pilates classes compared to in-studio classes in healthy sedentary women. In a randomized controlled design, 40 women, aged 20–45, were assigned to a Zoom or studio group-Pilates training. The intervention included twice-weekly 45 min sessions over an eight-week period. Attendance (adherence) was recorded, and the participants completed physical motor tests (plank, curl-up, stork, push-up, and V-sit and reach), Profile of Mood State Surveys, and Nordic Musculoskeletal Pain Questionnaires. Evaluations were performed at baseline, mid-intervention (4 weeks), and post intervention (8 weeks). Adherence to training was high in the Zoom and studio groups (80% and 74%, respectively). Improvements in physical motor tests were seen in both groups following the Pilates interventions, thereby indicating the effectiveness of group-Pilates Zoom training. In conclusion, remote online physical activity such as Pilates offers a good alternative to in-studio trainings, as a means for improving physical fitness and promoting a healthy lifestyle in adults, by offering a more accessible and less timely alternative to in-studio physical activity programs.
Exploring Experiences of Conflict within Medical Teams in an Emergency Department: A Focus Group Approach during the COVID-19 Pandemic
Authors: Fann Wen-Chih , Hsu Chih-Mimng , Hsiao Cheng-Ting , Lee Bih-O
Published: March 2024

The factors related to conflicts in emergency departments (EDs) have been studied for decades. The post-pandemic digital era may transform the medical landscape in EDs, potentially changing the patterns of conflict between healthcare professionals. This study used focus group interviews to explore conflicts in EDs. Four groups, each with 4–6 participants, took part in this study. Semi-structured interviews were conducted using six research questions. Summative content analysis was used to analyze the data. The participant’s average age was 37.82 years, and the average number of working years was 12.12. The following five themes emerged: multiple patterns of internal conflict; external conflicts arising from cross-departmental coordination; conflicts due to unclear job boundaries; adapting to conflicts in diverse ways; and seeking hospital arbitration. The results of this study suggest extending interdisciplinary collaborative practice from emergency departments to all coordinating departments. An inclusive environment for equality between professions and open communication should be promoted by hospitals.
Selective IgA Deficiency and Blood Component Transfusion: In Search of the Lost Evidence
Authors: Solves Pilar , Bataller Ana , Gálvez Ana Belén , Asensi Cantó Pedro , Santiago Marta , Moreno María José , Gómez-Seguí Inés , de la Rubia Javier
Published: March 2024

Background: Selective IgA deficiency (IgA-D) has been historically considered a high-risk entity for developing allergic/anaphylactic reactions after blood transfusion (AATRs). However, it has been suggested that the IgA-D-related anaphylactic transfusion reaction is not evidence-based. Methods: We conducted three different approaches to collect evidence about epidemiology, AATRs, and transfusion management of patients with IgA-D at La Fe University Hospital. Firstly, we analysed the prevalence of IgA-D in a population of patients diagnosed with acute leukaemia, The second approach consisted of collecting transfusion data from IgA-D patients. Finally, we reviewed the IgA levels of patients recorded in the hemovigilance system suffering an AATR. Results: IgA-D prevalence was 1 in 334 patients. At least one blood component was transfused to 23 patients diagnosed with IgA-D. Plasma was transfused to eight IgA-D patients, while six patients received red blood cells, platelets, and plasma. No adverse reactions were reported in any patient. AATRs occurred in 325 men and 264 women with a median age of 52 years. Severe reactions occurred in 56 patients (1/14,520 components). Mean IgA levels were 215 mg/dL (4–5570) for mild reactions and 214 mg/dL (14–824) for severe reactions (p = ns). Washed platelets were administered to two patients who developed severe and repeated AATRs. Both had normal IgA levels. Conclusions: Since the AATRs related to IgA-D are extremely low, as reported in current hemovigilance systems, IgA-D should not be considered a high-risk entity to develop AATRs. On the contrary, our findings support standard transfusion management of IgA-D patients.
On the SARS-CoV-2 Variants
Authors: Scarpa Fabio , Branda Francesco , Petrosillo Nicola , Ciccozzi Massimo
Published: March 2024

The evolutionary dynamics of viruses, particularly exemplified by SARS-CoV-2 during the ongoing COVID-19 pandemic, underscore the intricate interplay between genetics, host adaptation, and viral spread. This paper delves into the genetic evolution of SARS-CoV-2, emphasizing the implications of viral variants on global health. Initially emerging from the Wuhan-Hu-1 lineage, SARS-CoV-2 rapidly diversified into numerous variants, each characterized by distinct mutations in the spike protein and other genomic regions. Notable variants such as B.1.1.7 (α), B.1.351 (β), P.1 (γ), B.1.617.2 (δ), and the Omicron variant have garnered significant attention due to their heightened transmissibility and immune evasion capabilities. In particular, the Omicron variant has presented a myriad of subvariants, raising concerns about its potential impact on public health. Despite the emergence of numerous variants, the vast majority have exhibited limited expansion capabilities and have not posed significant threats akin to early pandemic strains. Continued genomic surveillance is imperative to identify emerging variants of concern promptly. While genetic adaptation is intrinsic to viral evolution, effective public health responses must be grounded in empirical evidence to navigate the evolving landscape of the pandemic with resilience and precision.
Current Progress and Future Perspectives in Contact and Releasing-Type Antimicrobial Coatings of Orthopaedic Implants: A Systematic Review Analysis Emanated from In Vitro and In Vivo Models
Authors: Kaspiris Angelos , Vasiliadis Elias , Pantazaka Evangelia , Lianou Ioanna , Melissaridou Dimitra , Savvidis Matthaios , Panagopoulos Fotios , Tsalimas Georgios , Vavourakis Michail , Kolovos Ioannis , Savvidou Olga D. , Pneumaticos Spiros G.
Published: March 2024

Background: Despite the expanding use of orthopedic devices and the application of strict pre- and postoperative protocols, the elimination of postoperative implant-related infections remains a challenge. Objectives: To identify and assess the in vitro and in vivo properties of antimicrobial-, silver- and iodine-based implants, as well as to present novel approaches to surface modifications of orthopedic implants. Methods: A systematic computer-based review on the development of these implants, on PubMed and Web of Science databases, was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Overall, 31 in vitro and 40 in vivo entries were evaluated. Regarding the in vitro studies, antimicrobial-based coatings were assessed in 12 entries, silver-based coatings in 10, iodine-based in 1, and novel-applied coating technologies in 8 entries. Regarding the in vivo studies, antimicrobial coatings were evaluated in 23 entries, silver-coated implants in 12, and iodine-coated in 1 entry, respectively. The application of novel coatings was studied in the rest of the cases (4). Antimicrobial efficacy was examined using different bacterial strains, and osseointegration ability and biocompatibility were examined in eukaryotic cells and different animal models, including rats, rabbits, and sheep. Conclusions: Assessment of both in vivo and in vitro studies revealed a wide antimicrobial spectrum of the coated implants, related to reduced bacterial growth, inhibition of biofilm formation, and unaffected or enhanced osseointegration, emphasizing the importance of the application of surface modification techniques as an alternative for the treatment of orthopedic implant infections in the clinical settings.
Investigating the Risk of Patient Manual Handling Using the Movement and Assistance of Hospital Patients Method among Hospital Nurses in Botswana
Authors: Kgakge Kagiso , Chelule Paul Kiprono , Kahere Morris , Ginindza Themba Geoffrey
Published: March 2024

Background: Evidence on the prevalence of lower back pain (LBP) among nurses is widespread in the literature, with several risk factors being reported. These include manual handling of patients, repetitive bending and twisting movements, and long working hours. It is reported that LBP has negative health outcomes and causes poor work performance among healthcare workers (HCWs). The magnitude of ergonomic risks associated with these healthcare activities has not been adequately investigated in Botswana. Thus, this study aimed to investigate the ergonomic risk levels associated with the manual handling of patients and its association with the prevalence of LBP among nurses in Botswana. Methods: This was an observational cross-sectional hospital-based study conducted in a Botswana public tertiary hospital from March to April 2023. The Movement and Assistance of Hospital Patients (MAPO) tool was used to collect data on ergonomic risk levels. Data on the demographic characteristics of participants were collected using a tool adapted from the Nordic Musculoskeletal Questionnaire (NMQ). Odds ratios and 95% confidence intervals were estimated to determine the association between ergonomic risk levels and the prevalence of LBP. Results: A total of 256 nurses participated and completed the study. The self-reported prevalence of LBP in this study was 76.6%. The risk of acquiring LBP was high (90.5%) based on the MAPO index. Although the frequencies of self-reported LBP were high among nurses, these did not show any significant association with the MAPO index data. This could be partly due to the small sample size. Conclusions: There was a high prevalence of LBP in this study, which was corroborated by the MAPO index data. This has demonstrated the value of the MAPO index in forecasting the risk of patient manual handling. The findings might help Botswana formulate policies intended to address ergonomic preventive measures, directed towards reducing the MAPO index score by addressing the single risk determinants.
Revisiting Urban Street Planning and Design Factors to Promote Walking as a Physical Activity for Middle-Class Individuals with Metabolic Syndrome in Cairo, Egypt
Authors: Abusaada Hisham , Elshater Abeer
Published: March 2024

This paper revisits the planning and design factors of “pedestrianized” and “walkable” urban streets to encourage physical activity, focusing on their prioritization according to public health and smart growth. The aim is to create a conceptual framework for urban planners and designers to encourage walking and reduce metabolic syndrome (MetS) risks. Through a scoping review, the study found that while pedestrianized and walkable streets share many planning and design factors, they have different objectives. The study explores how urban planning and design can reduce MetS risk among middle-class individuals using online video storytelling for 30 participants in three districts of Cairo, Egypt: El Zamalek, Old Cairo, and Heliopolis. It identifies three factors to address MetS symptoms for middle-class individuals: strategic, design-oriented, and technical. Practitioners and policymakers can use this framework to evaluate the impact of their work. This study is particularly relevant for cities in the Global South that are facing similar challenges.
Synthesis of Antiprotozoal 2-(4-Alkyloxyphenyl)-Imidazolines and Imidazoles and Their Evaluation on Leishmania mexicana and Trypanosoma cruzi
Authors: Torres-Jaramillo Jenifer , Blöcher René , Chacón-Vargas Karla Fabiola , Hernández-Calderón Jorge , Sánchez-Torres Luvia E. , Nogueda-Torres Benjamín , Reyes-Arellano Alicia
Published: March 2024

Twenty 2-(4-alkyloxyphenyl)-imidazolines and 2-(4-alkyloxyphenyl)-imidazoles were synthesized, with the former being synthesized in two steps by using MW and ultrasonication energy, resulting in good to excellent yields. Imidazoles were obtained in moderate yields by oxidizing imidazolines with MnO2 and MW energy. In response to the urgent need to treat neglected tropical diseases, a set of 2-(4-alkyloxyphenyl)- imidazolines and imidazoles was tested in vitro on Leishmania mexicana and Trypanosoma cruzi. The leishmanicidal activity of ten compounds was evaluated, showing an IC50 < 10 µg/mL. Among these compounds, 27–31 were the most active, with IC50 values < 1 µg/mL (similar to the reference drugs). In the evaluation on epimastigotes of T. cruzi, only 30 and 36 reached an IC50 < 1 µg/mL, showing better inhibition than both reference drugs. However, compounds 29, 33, and 35 also demonstrated attractive trypanocidal activities, with IC50 values < 10 µg/mL, similar to the values for benznidazole and nifurtimox.
Microscopic Menaces: The Impact of Mites on Human Health
Authors: Linn Christina , O’Malley Andrea , Khatri Kriti , Wright Elaine M. , Sebagh Dylan , Grbić Miodrag , Kowal Krzysztof , Chruszcz Maksymilian
Published: March 2024

Mites are highly prevalent arthropods that infest diverse ecological niches globally. Approximately 55,000 species of mites have been identified but many more are yet to be discovered. Of the ones we do know about, most go unnoticed by humans and animals. However, there are several species from the Acariformes superorder that exert a significant impact on global human health. House dust mites are a major source of inhaled allergens, affecting 10–20% of the world’s population; storage mites also cause a significant allergy in susceptible individuals; chiggers are the sole vectors for the bacterium that causes scrub typhus; Demodex mites are part of the normal microfauna of humans and their pets, but under certain conditions populations grow out of control and affect the integrity of the integumentary system; and scabies mites cause one of the most common dermatological diseases worldwide. On the other hand, recent genome sequences of mites provide novel tools for mite control and the development of new biomaterial with applications in biomedicine. Despite the palpable disease burden, mites remain understudied in parasitological research. By better understanding mite biology and disease processes, researchers can identify new ways to diagnose, manage, and prevent common mite-induced afflictions. This knowledge can lead to improved clinical outcomes and reduced disease burden from these remarkably widespread yet understudied creatures.
The Probiotic Lactobacillus reuteri Preferentially Synthesizes Kynurenic Acid from Kynurenine
Authors: Schwarcz Robert , Foo Ann , Sathyasaikumar Korrapati V. , Notarangelo Francesca M.
Published: March 2024

The gut–brain axis is increasingly understood to play a role in neuropsychiatric disorders. The probiotic bacterium Lactobacillus (L.) reuteri and products of tryptophan degradation, specifically the neuroactive kynurenine pathway (KP) metabolite kynurenic acid (KYNA), have received special attention in this context. We, therefore, assessed relevant features of KP metabolism, namely, the cellular uptake of the pivotal metabolite kynurenine and its conversion to its primary products KYNA, 3-hydroxykynurenine and anthranilic acid in L. reuteri by incubating the bacteria in Hank’s Balanced Salt solution in vitro. Kynurenine readily entered the bacterial cells and was preferentially converted to KYNA, which was promptly released into the extracellular milieu. De novo production of KYNA increased linearly with increasing concentrations of kynurenine (up to 1 mM) and bacteria (107 to 109 CFU/mL) and with incubation time (1–3 h). KYNA neosynthesis was blocked by two selective inhibitors of mammalian kynurenine aminotransferase II (PF-048559989 and BFF-122). In contrast to mammals, however, kynurenine uptake was not influenced by other substrates of the mammalian large neutral amino acid transporter, and KYNA production was not affected by the presumed competitive enzyme substrates (glutamine and α-aminoadipate). Taken together, these results reveal substantive qualitative differences between bacterial and mammalian KP metabolism.
Propranolol Promotes Monocyte-to-Macrophage Differentiation and Enhances Macrophage Anti-Inflammatory and Antioxidant Activities by NRF2 Activation
Authors: Maccari Sonia , Profumo Elisabetta , Saso Luciano , Marano Giuseppe , Buttari Brigitta
Published: March 2024

Adrenergic pathways represent the main channel of communication between the nervous system and the immune system. During inflammation, blood monocytes migrate within tissue and differentiate into macrophages, which polarize to M1 or M2 macrophages with tissue-damaging or -reparative properties, respectively. This study investigates whether the β-adrenergic receptor (β-AR)-blocking drug propranolol modulates the monocyte-to-macrophage differentiation process and further influences macrophages in their polarization toward M1- and M2-like phenotypes. Six-day-human monocytes were cultured with M-CSF in the presence or absence of propranolol and then activated toward an M1 pro-inflammatory state or an M2 anti-inflammatory state. The chronic exposure of monocytes to propranolol during their differentiation into macrophages promoted the increase in the M1 marker CD16 and in the M2 markers CD206 and CD163 and peroxisome proliferator-activated receptor ɣ expression. It also increased endocytosis and the release of IL-10, whereas it reduced physiological reactive oxygen species. Exposure to the pro-inflammatory conditions of propranolol-differentiated macrophages resulted in an anti-inflammatory promoting effect. At the molecular level, propranolol upregulated the expression of the oxidative stress regulators NRF2, heme oxygenase-1 and NQO1. By contributing to regulating macrophage activities, propranolol may represent a novel anti-inflammatory and immunomodulating compound with relevant therapeutic potential in several inflammatory diseases.
Tobacco Transcription Factor NtWRKY70b Facilitates Leaf Senescence via Inducing ROS Accumulation and Impairing Hydrogen Sulfide Biosynthesis
Authors: Zhang Xinshuang , Sun Yan , Wu Hao , Zhu Ying , Liu Xin , Lu Songchong
Published: March 2024

Leaf senescence is the terminal stage of leaf development, and its initiation and progression are closely controlled by the integration of a myriad of endogenous signals and environmental stimuli. It has been documented that WRKY transcription factors (TFs) play essential roles in regulating leaf senescence, yet the molecular mechanism of WRKY-mediated leaf senescence still lacks detailed elucidation in crop plants. In this study, we cloned and identified a tobacco WRKY TF gene, designated NtWRKY70b, acting as a positive regulator of natural leaf senescence. The expression profile analysis showed that NtWRKY70b transcript levels were induced by aging and hydrogen peroxide (H2O2) and downregulated upon hydrogen sulfide (H2S) treatment. The physiological and biochemical assays revealed that overexpression of NtWRKY70b (OE) clearly promoted leaf senescence, triggering increased levels of reactive oxygen species (ROS) and decreased H2S content, while disruption of NtWRKY70b by chimeric repressor silencing technology (SRDX) significantly delayed the onset of leaf senescence, leading to a decreased accumulation of ROS and elevated concentration of H2S. The quantitative real-time PCR analysis showed that the expression levels of various senescence-associated genes and ROS biosynthesis-related genes (NtRbohD and NtRbohE) were upregulated in OE lines, while the expression of H2S biosynthesis-related genes (NtDCD and NtCYSC1) were inhibited in OE lines. Furthermore, the Yeast one-hybrid analysis (Y1H) and dual luciferase assays showed that NtWRKY70b could directly upregulate the expression of an ROS biosynthesis-related gene (NtRbohD) and a chlorophyll degradation-related gene (NtPPH) by binding to their promoter sequences. Accordingly, these results indicated that NtWYKY70b directly activated the transcript levels of NtRbohD and NtPPH and repressed the expression of NtDCD and NtCYCS1, thereby promoting ROS accumulation and impairing the endogenous H2S production, and subsequently accelerating leaf aging. These observations improve our knowledge of the regulatory mechanisms of WRKY TFs controlling leaf senescence and provide a novel method for ensuring high agricultural crop productivity via genetic manipulation of leaf senescence in crops.
Retinal Neurodegeneration in an Intraocular Pressure Fluctuation Rat Model
Authors: Han Jeong-Sun , Park Chan Kee , Jung Kyoung In
Published: March 2024

Increased intraocular pressure (IOP) is the most important risk factor for glaucoma. The role of IOP fluctuation, independently from elevated IOP, has not yet been confirmed in glaucoma. We investigated the effects of IOP fluctuation itself on retinal neurodegeneration. Male rats were treated with IOP-lowering eyedrops (brinzolamide and latanoprost) on Mondays and Thursdays (in the irregular instillation group) or daily (in the regular instillation group), and saline was administered daily in the normal control group for 8 weeks. The IOP standard deviation was higher in the irregular instillation group than the regular instillation group or the control group. The degree of oxidative stress, which was analyzed by labeling superoxide, oxidative DNA damage, and nitrotyrosine, was increased in the irregular instillation group. Macroglial activation, expressed by glial fibrillary acidic protein in the optic nerve head and retina, was observed with the irregular instillation of IOP-lowering eyedrops. Microglial activation, as indicated by Iba-1, and the expression of TNF-α did not show a significant difference between the irregular instillation and control groups. Expression of cleaved caspase-3 was upregulated and the number of retinal ganglion cells (RGCs) was decreased in the irregular instillation group. Our findings indicate that IOP fluctuations could be induced by irregular instillation of IOP-lowering eyedrops and this could lead to the degeneration of RGCs, probably through increased oxidative stress and macrogliosis.
Prognostic Value of Liquid-Biopsy-Based Biomarkers in Upper Tract Urothelial Carcinoma
Authors: Padullés Bernat , Carrasco Raquel , Ingelmo-Torres Mercedes , Roldán Fiorella L. , Gómez Ascensión , Vélez Elena , Alfambra Héctor , Figueras Marcel , Carrion Albert , Gil-Vernet Jordi , Mengual Lourdes , Izquierdo Laura , Alcaraz Antonio
Published: March 2024

Currently, there are no reliable prognostic factors to determine which upper tract urothelial carcinoma (UTUC) patients will progress after radical nephroureterectomy (RNU). We aim to evaluate whether liquid-biopsy-based biomarkers (circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA)) were able to predict clinical outcomes in localized UTUC patients undergoing RNU. Twenty patients were prospectively enrolled between 2021 and 2023. Two blood samples were collected before RNU and three months later. CTCs and cfDNA were isolated and evaluated using the IsoFlux system and Quant-iT PicoGreen dsDNA kit, respectively. Droplet digital PCR was performed to determine ctDNA status. Cox regression analysis was performed on CTCs, cfDNA, and ctDNA at two different follow-up time points to examine their influence on tumor progression and cancer-specific survival (CSS). During a median follow-up of 18 months, seven (35%) patients progressed and three (15%) died. Multivariate analysis demonstrated that cfDNA levels three months after RNU are a significant predictor of tumor progression (HR = 1.085; p = 0.006) and CSS (HR = 1.168; p = 0.029). No associations were found between CTC enumeration and ctDNA status with any of the clinical outcomes evaluated. The evaluation of cfDNA levels in clinical practice could improve the disease management of UTUC patients.
Properties and Mechanisms of Deletions, Insertions, and Substitutions in the Evolutionary History of SARS-CoV-2
Authors: Rogozin Igor B. , Saura Andreu , Poliakov Eugenia , Bykova Anastassia , Roche-Lima Abiel , Pavlov Youri I. , Yurchenko Vyacheslav
Published: March 2024

SARS-CoV-2 has accumulated many mutations since its emergence in late 2019. Nucleotide substitutions leading to amino acid replacements constitute the primary material for natural selection. Insertions, deletions, and substitutions appear to be critical for coronavirus’s macro- and microevolution. Understanding the molecular mechanisms of mutations in the mutational hotspots (positions, loci with recurrent mutations, and nucleotide context) is important for disentangling roles of mutagenesis and selection. In the SARS-CoV-2 genome, deletions and insertions are frequently associated with repetitive sequences, whereas C>U substitutions are often surrounded by nucleotides resembling the APOBEC mutable motifs. We describe various approaches to mutation spectra analyses, including the context features of RNAs that are likely to be involved in the generation of recurrent mutations. We also discuss the interplay between mutations and natural selection as a complex evolutionary trend. The substantial variability and complexity of pipelines for the reconstruction of mutations and the huge number of genomic sequences are major problems for the analyses of mutations in the SARS-CoV-2 genome. As a solution, we advocate for the development of a centralized database of predicted mutations, which needs to be updated on a regular basis.
The First Korean Case with Cardiac, Facial, and Digital Anomalies with Developmental Delay Caused by De Novo TRAF7 p.Arg655Gln Variant
Authors: Kim Kyung Hee , Han Ji Yoon , Park Joonhong , Cho Jung Sun
Published: March 2024

TRAF7-related disorders represent some of the rarest inherited disorders, exhibiting clinical features that overlap with cardiac, facial, and digital anomalies with developmental delay (CAFDADD) syndrome, as well as blepharophimosis-mental retardation syndrome (BMRS). A 36-year-old male, presenting with total blindness, blepharophimosis, and intellectual disability, was admitted for the assessment of resting dyspnea several months previously. He had a history of being diagnosed with obstructive sleep apnea (OSA). Transesophageal and transthoracic echocardiography unveiled right ventricular dilatation without significant pulmonary hypertension, bicuspid aortic valve with aortic root aneurysm, and aortic regurgitation in the proband. Sanger sequencing identified a de novo TRAF7 variant (c.1964G>A; p.Arg655Gln). Subsequently, aortic root replacement using the Bentall procedure was performed. However, despite the surgery, he continued to experience dyspnea. Upon re-evaluating OSA with polysomnography, it was discovered that continuous positive airway pressure support alleviated his symptoms. The underlying cause of his symptoms was attributed to OSA, likely exacerbated by the vertebral anomaly and short neck associated with CAFDADD syndrome. Clinicians should be attentive to the symptoms associated with OSA as it is a potentially serious medical condition in patients with TRAF7 variants.
ETV6::NTRK3 Fusion-Positive Wild-Type Gastrointestinal Stromal Tumor (GIST) with Abundant Lymphoid Infiltration (TILs and Tertiary Lymphoid Structures): A Report on a New Case with Therapeutic Implications and a Literature Review
Authors: Machado Isidro , Claramunt-Alonso Reyes , Lavernia Javier , Romero Ignacio , Barrios María , Safont María José , Santonja Nuria , Navarro Lara , López-Guerrero José Antonio , Llombart-Bosch Antonio
Published: March 2024

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, with proto-oncogene, receptor tyrosine kinase (c-kit), or PDGFRα mutations detected in around 85% of cases. GISTs without c-kit or platelet-derived growth factor receptor alpha (PDGFRα) mutations are considered wild-type (WT), and their diverse molecular alterations and biological behaviors remain uncertain. They are usually not sensitive to tyrosine kinase inhibitors (TKIs). Recently, some molecular alterations, including neurotrophic tyrosine receptor kinase (NTRK) fusions, have been reported in very few cases of WT GISTs. This novel finding opens the window for the use of tropomyosin receptor kinase (TRK) inhibitor therapy in these subtypes of GIST. Herein, we report a new case of NTRK-fused WT high-risk GIST in a female patient with a large pelvic mass (large dimension of 20 cm). The tumor was removed, and the histopathology displayed spindle-predominant morphology with focal epithelioid areas, myxoid stromal tissue, and notable lymphoid infiltration with tertiary lymphoid structures. Ten mitoses were quantified in 50 high-power fields without nuclear pleomorphism. DOG1 showed strong and diffuse positivity, and CD117 showed moderate positivity. Succinate dehydrogenase subunit B (SDHB) was retained, Pan-TRK was focal positive (nuclear pattern), and the proliferation index Ki-67 was 7%. Next-generation sequencing (NGS) detected an ETV6::NTRK3 fusion, and this finding was confirmed by fluorescence in situ hybridization (FISH), which showed NTRK3 rearrangement. In addition, an RB1 mutation was found by NGS. The follow-up CT scan revealed peritoneal nodules suggestive of peritoneal dissemination, and Entrectinib (a TRK inhibitor) was administered. After 3 months of follow-up, a new CT scan showed a complete response. Based on our results and the cases from the literature, GISTs with NTRK fusions are very uncommon so far; hence, further screening studies, including more WT GIST cases, may increase the possibility of finding additional cases. The present case may offer new insights into the potential introduction of TRK inhibitors as treatments for GISTs with NTRK fusions. Additionally, the presence of abundant lymphoid infiltration in the present case may prompt further research into immunotherapy as a possible additional therapeutic option.
Dihydroergotamine Increases Histamine Brain Levels and Improves Memory in a Scopolamine-Induced Amnesia Model
Authors: Hernández-Rodríguez Maricarmen , Mera Jiménez Elvia , Nicolás-Vázquez María Inés , Miranda-Ruvalcaba Rene
Published: March 2024

The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory impairments. In addition, by employing drug repurposing approaches, it was demonstrated that dihydroergotamine (DHE), an FDA drug approved to treat migraines, inhibits Histamine N Methyl Transferase (HNMT), the enzyme responsible for the inactivation of histamine in the brain. For this reason, in the present work, the effect of DHE on histamine levels in the hippocampus and its effects on memory was evaluated, employing the scopolamine-induced amnesia model, the Novel Object Recognition (NOR) paradigm, and the Morris Water Maze (MWM). Furthermore, the role of histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists in the improvement in memory produced by DHE in the scopolamine-induced amnesia model was evaluated. Results showed that the rats that received DHE (10 mg/kg, i.p.) showed increased histamine levels in the hippocampus after 1 h of administration but not after 5 h. In behavioral assays, it was shown that DHE (1 mg/kg, i.p.) administered 20 min before the training reversed the memory impairment produced by the administration of scopolamine (2 mg/kg, i.p.) immediately after the training in the NOR paradigm and MWM. Additionally, the effects in memory produced by DHE were blocked by pre-treatment with pyrilamine (20 mg/kg, i.p.) administered 30 min before the training in the NOR paradigm and MWM. These findings allow us to demonstrate that DHE improves memory in a scopolamine-induced amnesia model through increasing histamine levels at the hippocampus due to its activity as an HNMT inhibitor.
Perioperative Ketamine and Cancer Recurrence: A Comprehensive Review
Authors: Rodriguez Arango Juan Alberto , Zec Tamara , Khalife Maher
Published: March 2024

Cancer is a significant global health threat and a leading cause of death worldwide. Effective early-stage interventions, particularly surgery, can potentially cure many solid tumors. However, the risk of postoperative cancer recurrence remains high. Recent research highlights the influence of perioperative anesthetic and analgesic choices on the fate of residual cancer cells, potentially affecting recurrence risks. Among these agents, ketamine—a well-known anesthetic and analgesic—has garnered interest due to its antitumor properties, mainly through inhibiting the N-methyl-D-aspartate (NMDA) receptor found in various cancer tissues. Additionally, ketamine’s potential immunomodulatory effects, given the expression of NMDA receptors on immune cells, suggest that it plays a significant role during the perioperative period. This review synthesizes current evidence on ketamine’s impact on cancer cell biology, inflammation, immune modulation, and the role of the gut microbiota, proposing ketamine as a promising agent for enhancing oncological outcomes.
Numerical Study of an Innovative Concept for a Multibody Anti-Pitching Semi-Submersible Floating Wind Turbine
Authors: Fan Tianhui , Fang Jianhu , Yan Xinkuan , Ma Yuan
Published: March 2024

The floating offshore wind turbine provides a feasible solution for the development of renewable ocean energy. However, the sizeable rotor diameter of the wind turbine results in large wind heeling moments and pitch amplitude. It will increase the structural loads and cause safety problems. Additionally, the contradictory nature between the stability and the sea-keeping of the floating structure requires that the more flexible method should be adopted to reduce the motion response of the floating offshore wind turbine. Therefore, an innovative concept of a multibody anti-pitching semi-submersible floating offshore wind turbine, named the MBAPSF, is proposed in this paper. The MBAPSF consists of a 5 MW braceless semi-submersible wind turbine and three wave energy converters. The multibody coupled numerical model is established by using an F2A tool, and the dynamic performance of the MBAPSF is compared with that of the traditional semi-submersible wind turbine named the TSSF. The results show that the innovative concept proposed in this paper can reduce pitch motion up to approximately 27% under different load cases, and the maximum bending moment and shearing force at the tower base are also reduced by more than 10%. Meanwhile, WECs are beneficial for increases in the total power generation capacity.