bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Spatial Resolutions on Nature-Based Solution Suitability Mapping for Europe
Authors: Ommer Joy , Neumann Jessica , Vranić Saša , Kalas Milan , Leo Laura Sandra , Di Sabatino Silvana , Cloke Hannah Louise
Published: May 2024

Flooding events, like in Germany in 2021, highlight the need for re-naturalising banks of rivers and streams to naturally mitigate future flooding. To identify potential areas for Nature-Based Solutions (NBS), the NBS Toolkit—a decision-support tool for Europe—was developed within the H2020 OPERANDUM project. The tool builds on suitability mapping, which is progressively adopted for pre-assessing areas for Nature-Based Solutions. The NBS Toolkit operates with European open-source data, which is available at different spatial resolutions. In this study, we performed a GIS-based analysis to examine the impact of different resolution data on the resulting suitability maps. The results suggest that for large-scale measures such as riparian forest buffers, coarser resolutions are sufficient and may save processing time and capacities. However, fine resolution datasets can bring added value to urban suitability mapping and are of greater importance for small-scale, local Nature-Based Solutions.
Design and Implementation of Adam: A Humanoid Robotic Head with Social Interaction Capabilities
Authors: Said Sherif , Youssef Karim , Prasad Benrose , Alasfour Ghaneemah , Alkork Samer , Beyrouthy Taha
Published: May 2024

Social robots are being conceived with different characteristics and being used in different applications. The growth of social robotics benefits from advances in fabrication, sensing, and actuation technologies, as well as signal processing and artificial intelligence. This paper presents a design and implementation of the humanoid robotic platform Adam, consisting of a motorized human-like head with precise movements of the eyes, jaw, and neck, together with capabilities of face tracking and vocal conversation using ChatGPT. Adam relies on 3D-printed parts together with a microphone, a camera, and proper servomotors, and it has high structural integrity and flexibility. Adam’s control framework consists of an adequate signal exploitation and motor command strategy that allows efficient social interactions. Adam is an innovative platform that combines manufacturability, user-friendliness, low costs, acceptability, and sustainability, offering advantages compared with other platforms. Indeed, the platform’s hardware and software components are adjustable and allow it to increase its abilities and adapt them to different applications in a variety of roles. Future work will entail the development of a body for Adam and the addition of skin-like materials to enhance its human-like appearance.
Exploring the Effects of Elevated Ozone Concentration on Physiological Processes in Summer Maize in North China Based on Exposure–Response Relationships
Authors: Wang Mansen , Xie Shuyang , Lun Xiaoxiu , He Zhouming , Liu Xin , Lv Wenjun , Wang Luxi , Wang Tian , Liu Junfeng
Published: May 2024

As the predominant pollutant in North China during the summer months, ozone (O3) exhibits strong oxidizing capabilities. Long-term exposure of crops to ozone will cause a decrease in various physiological indicators, affect crop yields, and pose a serious threat to food security. The North China Plain, the primary region for summer maize production in China, is afflicted by ozone pollution. In order to explore the effects of increasing O3 concentration on the physiological characteristics and photosynthetic characteristics of summer maize, this study took summer-sown maize as the research object and carried out the ozone exposure experiment with open-top chamber (OTCs). The response of maize to O3 exposure was studied by measuring the damage, physiological indexes and photosynthetic indexes in the silking stage (late July to late August) and filling stage (late August to mid-September). The results indicated the following: (1) Prolonged exposure to high O3 concentrations exacerbated leaf chlorosis and damage. (2) The increase in O3 concentration caused lipid peroxidation. The content of malondialdehyde was significantly increased by 32.6%~122.56%. At the same time, chlorophyll was destroyed and decreased by 2.17% to 4.86%. Under ozone exposure, ascorbic acid content was significantly increased by 7.58%~35.69%. The antioxidant indexes of maize were more sensitive during the filling stage. (3) Under O3 exposure, photosynthetic rate, stomatal conductance and intercellular carbon dioxide concentration decreased significantly, indicating that the influence of O3 on maize was mainly due to stomatal limitation. Water use efficiency and transpiration rate decreased significantly. The water use efficiency decreased by 12.84%~35.62%, which led to the weakening of the carbon fixation ability of maize and affected the normal growth and development of maize.
Generation of Tailored Extracellular Matrix Hydrogels for the Study of In Vitro Folliculogenesis in Response to Matrisome-Dependent Biochemical Cues
Authors: McDowell Hannah B. , McElhinney Kathryn L. , Tsui Elizabeth L. , Laronda Monica M.
Published: May 2024

While ovarian tissue cryopreservation (OTC) is an important fertility preservation option, it has its limitations. Improving OTC and ovarian tissue transplantation (OTT) must include extending the function of reimplanted tissue by reducing the extensive activation of primordial follicles (PMFs) and eliminating the risk of reimplanting malignant cells. To develop a more effective OTT, we must understand the effects of the ovarian microenvironment on folliculogenesis. Here, we describe a method for producing decellularized extracellular matrix (dECM) hydrogels that reflect the protein composition of the ovary. These ovarian dECM hydrogels were engineered to assess the effects of ECM on in vitro follicle growth, and we developed a novel method for selectively removing proteins of interest from dECM hydrogels. Finally, we validated the depletion of these proteins and successfully cultured murine follicles encapsulated in the compartment-specific ovarian dECM hydrogels and these same hydrogels depleted of EMILIN1. These are the first, optically clear, tailored tissue-specific hydrogels that support follicle survival and growth comparable to the “gold standard” alginate hydrogels. Furthermore, depleted hydrogels can serve as a novel tool for many tissue types to evaluate the impact of specific ECM proteins on cellular and molecular behavior.
Evaluation of Patients’ Levels of Walking Independence Using Inertial Sensors and Neural Networks in an Acute-Care Hospital
Authors: Sugimoto Tatsuya , Taniguchi Nobuhito , Yoshikura Ryoto , Kawaguchi Hiroshi , Izumi Shintaro
Published: May 2024

This study aimed to evaluate walking independence in acute-care hospital patients using neural networks based on acceleration and angular velocity from two walking tests. Forty patients underwent the 10-m walk test and the Timed Up-and-Go test at normal speed, with or without a cane. Physiotherapists divided the patients into two groups: 24 patients who were monitored or independent while walking with a cane or without aids in the ward, and 16 patients who were not. To classify these groups, the Transformer model analyzes the left gait cycle data from eight inertial sensors. The accuracy using all the sensor data was 0.836. When sensor data from the right ankle, right wrist, and left wrist were excluded, the accuracy decreased the most. When analyzing the data from these three sensors alone, the accuracy was 0.795. Further reducing the number of sensors to only the right ankle and wrist resulted in an accuracy of 0.736. This study demonstrates the potential of a neural network-based analysis of inertial sensor data for clinically assessing a patient’s level of walking independence.
LightCF-Net: A Lightweight Long-Range Context Fusion Network for Real-Time Polyp Segmentation
Authors: Ji Zhanlin , Li Xiaoyu , Liu Jianuo , Chen Rui , Liao Qinping , Lyu Tao , Zhao Li
Published: May 2024

Automatically segmenting polyps from colonoscopy videos is crucial for developing computer-assisted diagnostic systems for colorectal cancer. Existing automatic polyp segmentation methods often struggle to fulfill the real-time demands of clinical applications due to their substantial parameter count and computational load, especially those based on Transformer architectures. To tackle these challenges, a novel lightweight long-range context fusion network, named LightCF-Net, is proposed in this paper. This network attempts to model long-range spatial dependencies while maintaining real-time performance, to better distinguish polyps from background noise and thus improve segmentation accuracy. A novel Fusion Attention Encoder (FAEncoder) is designed in the proposed network, which integrates Large Kernel Attention (LKA) and channel attention mechanisms to extract deep representational features of polyps and unearth long-range dependencies. Furthermore, a newly designed Visual Attention Mamba module (VAM) is added to the skip connections, modeling long-range context dependencies in the encoder-extracted features and reducing background noise interference through the attention mechanism. Finally, a Pyramid Split Attention module (PSA) is used in the bottleneck layer to extract richer multi-scale contextual features. The proposed method was thoroughly evaluated on four renowned polyp segmentation datasets: Kvasir-SEG, CVC-ClinicDB, BKAI-IGH, and ETIS. Experimental findings demonstrate that the proposed method delivers higher segmentation accuracy in less time, consistently outperforming the most advanced lightweight polyp segmentation networks.
Mechanical Method for Rapid Determination of Step Count Sensor Settings
Authors: Lundell Sydney , Kaufman Kenton R.
Published: May 2024

With the increased push for personalized medicine, researchers and clinicians have begun exploring the use of wearable sensors to track patient activity. These sensors typically prioritize device life over robust onboard analysis, which results in lower accuracies in step count, particularly at lower cadences. To optimize the accuracy of activity-monitoring devices, particularly at slower walking speeds, proven methods must be established to identify suitable settings in a controlled and repeatable manner prior to human validation trials. Currently, there are no methods for optimizing these low-power wearable sensor settings prior to human validation, which requires manual counting for in-laboratory participants and is limited by time and the cadences that can be tested. This article proposes a novel method for determining sensor step counting accuracy prior to human validation trials by using a mechanical camshaft actuator that produces continuous steps. Sensor error was identified across a representative subspace of possible sensor setting combinations at cadences ranging from 30 steps/min to 110 steps/min. These true errors were then used to train a multivariate polynomial regression to model errors across all possible setting combinations and cadences. The resulting model predicted errors with an R2 of 0.8 and root-mean-square error (RMSE) of 0.044 across all setting combinations. An optimization algorithm was then used to determine the combinations of settings that produced the lowest RMSE and median error for three ranges of cadence that represent disabled low-mobility ambulators, disabled high-mobility ambulators, and healthy ambulators (30–60, 20–90, and 30–110 steps/min, respectively). The model identified six setting combinations for each range of interest that achieved a ±10% error in cadence prior to human validation. The anticipated range of errors from the optimized settings at lower walking speeds are lower than the reported errors of wearable sensors (±30%), suggesting that pre-human-validation optimization of sensors may decrease errors at lower cadences. This method provides a novel and efficient approach to optimizing the accuracy of wearable activity monitors prior to human validation trials.
Standards and Metrology for Viral Vectors as Molecular Tools: Outcomes from a CCQM Workshop
Authors: Campbell Jonathan J. , Almond Neil , Bae Young-Kyong , Bhuller Ravneet , Briones Andrea , Cho Sang-Joon , Cleveland Megan H. , Cleveland Thomas E. , Galaway Francis , He Hua-Jun , Herbrand Ulrike , Huggett Jim F. , Kempster Sarah , Kepiro Ibolya E. , Khan Arifa S. , Kwee Edward , Li Wilson , Lin-Gibson Sheng , Luckau Luise , Minelli Caterina , Ryadnov Maxim G. , Searing Isobel , Wang Lili , Whale Alexandra S. , Braybrook Julian H.
Published: May 2024

Viral vectors are agents enabling gene transfer and genome editing and have widespread utility across the healthcare and biotechnology sectors. In January 2023, the International Bureau for Weights and Measures’ Consultative Committee for Amount of Substance (CCQM) held a workshop on Metrology for Viral systems as molecular tools. The workshop brought together international leaders from across regulatory, industry, government science, and metrology sectors to better understand key challenges for the community: Exploring current limitations in the measurement of virus-derived, virus-based, and virus-like systems in terms of quantification and characterisation; surveying the state-of-the-art in analytical methods and reference material provision for these entities; and initiating a dialog for the strategic development and implementation of suitable standardisation approaches for this sector. This article presents the workshop background and rationale, presentation summaries, conclusions, and recommendations.
Modulation of Glucose Consumption and Uptake in HepG2 Cells by Aqueous Extracts from the Coelomic Fluid of the Edible Holothuria tubulosa Sea Cucumber
Authors: Abruscato Giulia , Tarantino Roberta , Mauro Manuela , Chiarelli Roberto , Vizzini Aiti , Arizza Vincenzo , Vazzana Mirella , Luparello Claudio
Published: May 2024

The cell-free aqueous extract from the coelomic fluid of Holothuria tubulosa was prepared and examined for its glucose-lowering effect on HepG2 cells in vitro. In particular, employing a combination of cytochemical, flow cytometric, PCR, and protein blot techniques, we evaluated its role on glucose internalization and storage and on the upregulation and surface translocation of the two glucose transporters GLUT-2 and -4. The changes in expression, synthesis, and/or activation of the GLUT2-related transcription factor hepatocyte nuclear factor-1 alpha (HNF1α) and the GLUT-4-translocation regulatory factors insulin receptor substrate-1 (IRS-1) and AKT were also studied. Our results showed the improved glucose response by HepG2 cells, leading to an evident increase in glucose consumption/uptake and glycogen storage upon exposure. Moreover, the extract induced molecular reprogramming involving the upregulation of (i) IRS1 gene expression, (ii) the transcription and translation levels of HNF1α, AKT, and GLUT-4, (iii) the phosphorylation level of AKT, (iv) the synthesis of GLUT-2 protein, and (v) the translocation of GLUT-2 and -4 transporters onto the plasma membrane. Cumulatively, our results suggest that the coelomic fluid extract from H. tubulosa can be taken into consideration for the development of novel treatment agents against diabetes mellitus.
The Structure of Digestive Tract Coordinating Digestion and Respiration in an Air-Breathing Weatherloach, Misgurnus anguillicaudatus
Authors: Qi Zixin , Ma Hongbo , Ma Li , Yang Xuefen
Published: May 2024

To clarify how the digestive tract of the weatherloach, Misgurnus anguillicaudatus, serves a dual function of digestion and respiration simultaneously, the histological structures of its digestive tract, the passage of digesta and air passing through its intestine and the rate of intestinal evacuation have been studied. The results indicate that the digestive tract is divided into five functional regions, i.e., esophagus, anterior intestine, middle intestine, posterior intestine and rectum. The diverse intestinal structures have the specialized function of coordinating digestion and respiration. An X-ray barium meal examination showed in the normal breathing state, the contents of the intestine are diffusely semifluid, and air is distributed as bubbles in the dorsal intestine 2 h after feeding. After 5 h, the contents accumulated in the mid and posterior intestine, and gas flowed above the contents as bundles. After 8 h, the intestinal food was basically evacuated. In the intestinal air-breathing restricted group, the contents of the intestine remained diffuse, and a large number of digesta entered and remained in the rectum after 5 h. After the inhibition was relieved, the contents of the rectum were rapidly discharged. Measurement of the intestinal evacuation rate in the intestine showed that the evacuation of the intestinal contents lagged behind that of the normal group in the air-breathing restricted group. Compared to the normal state and inhibited GAB (gastrointestinal air breathing), we could deduce that GAB could promote the movement of the intestine.
Identification of Gut Microbiome Signatures Associated with Indole Pathway in Tryptophan Metabolism in Patients Undergoing Hemodialysis
Authors: Huang Jih-Kai , Wu Ping-Hsun , Chen Zhao-Feng , Liu Po-Yu , Kuo Cheng-Chin , Chuang Yun-Shiuan , Lu Meng-Zhan , Kuo Mei-Chuan , Chiu Yi-Wen , Lin Yi-Ting
Published: May 2024

Microbiota tryptophan metabolism and the biosynthesis of indole derivatives play an important role in homeostasis and pathogenesis in the human body and can be affected by the gut microbiota. However, studies on the interplay between gut microbiota and tryptophan metabolites in patients undergoing dialysis are lacking. This study aimed to identify the gut microbiota, the indole pathway in tryptophan metabolism, and significant functional differences in ESRD patients with regular hemodialysis. We performed the shotgun metagenome sequencing of stool samples from 85 hemodialysis patients. Using the linear discriminant analysis effect size (LEfSe), we examined the composition of the gut microbiota and metabolic features across varying concentrations of tryptophan and indole metabolites. Higher tryptophan levels promoted tyrosine degradation I and pectin degradation I metabolic modules; lower tryptophan levels were associated with glutamate degradation I, fructose degradation, and valine degradation modules. Higher 3-indoxyl sulfate concentrations were characterized by alanine degradation I, anaerobic fatty acid beta-oxidation, sulfate reduction, and acetyl-CoA to crotonyl-CoA. Contrarily, lower 3-indoxyl sulfate levels were related to propionate production III, arabinoxylan degradation, the Entner–Doudoroff pathway, and glutamate degradation II. The present study provides a better understanding of the interaction between tryptophan, indole metabolites, and the gut microbiota as well as their gut metabolic modules in ESRD patients with regular hemodialysis.
Encapsulated Ferritin-like Proteins: A Structural Perspective
Authors: Eren Elif , Watts Norman R. , Montecinos Felipe , Wingfield Paul T.
Published: May 2024

Encapsulins are self-assembling nano-compartments that naturally occur in bacteria and archaea. These nano-compartments encapsulate cargo proteins that bind to the shell’s interior through specific recognition sequences and perform various metabolic processes. Encapsulation enables organisms to perform chemical reactions without exposing the rest of the cell to potentially harmful substances while shielding cargo molecules from degradation and other adverse effects of the surrounding environment. One particular type of cargo protein, the ferritin-like protein (FLP), is the focus of this review. Encapsulated FLPs are members of the ferritin-like protein superfamily, and they play a crucial role in converting ferrous iron (Fe+2) to ferric iron (Fe+3), which is then stored inside the encapsulin in mineralized form. As such, FLPs regulate iron homeostasis and protect organisms against oxidative stress. Recent studies have demonstrated that FLPs have tremendous potential as biosensors and bioreactors because of their ability to catalyze the oxidation of ferrous iron with high specificity and efficiency. Moreover, they have been investigated as potential targets for therapeutic intervention in cancer drug development and bacterial pathogenesis. Further research will likely lead to new insights and applications for these remarkable proteins in biomedicine and biotechnology.
BUB1 Inhibition Sensitizes TNBC Cell Lines to Chemotherapy and Radiotherapy
Authors: Sriramulu Sushmitha , Thoidingjam Shivani , Siddiqui Farzan , Brown Stephen L. , Movsas Benjamin , Walker Eleanor , Nyati Shyam
Published: May 2024

BUB1 is overexpressed in most human solid cancers, including breast cancer. Higher BUB1 levels are associated with a poor prognosis, especially in patients with triple-negative breast cancer (TNBC). Women with TNBC often develop resistance to chemotherapy and radiotherapy, which are still the mainstay of treatment for TNBC. Our previous studies demonstrated that a BUB1 kinase inhibitor (BAY1816032) reduced tumor cell proliferation and significantly enhanced radiotherapy efficacy in TNBC. In this study, we evaluated the effectiveness of BAY1816032 with a PARP inhibitor (olaparib), platinum agent (cisplatin), and microtubule poison (paclitaxel) alone or in combination with radiotherapy using cytotoxicity and clonogenic survival assays. BUB1 inhibitors sensitized BRCA1/2 wild-type SUM159 and MDA-MB-231 cells to olaparib, cisplatin, and paclitaxel synergistically (combination index; CI < 1). BAY1816032 significantly increased the radiation sensitization of SUM159 and MDA-MB-231 by olaparib, cisplatin, or paclitaxel at non-toxic concentrations (doses well below the IC50 concentrations). Importantly, the small molecular inhibitor of BUB1 synergistically (CI < 1) sensitized the BRCA mutant TNBC cell line HCC1937 to olaparib. Furthermore, the BUB1 inhibitor significantly increased the radiation enhancement ratio (rER) in HCC1937 cells (rER 1.34) compared to either agent alone (BUB1i rER 1.19; PARPi rER 1.04). The data presented here are significant as they provide proof that inhibition of BUB1 kinase activity sensitizes TNBC cell lines to a PARP inhibitor and radiation, irrespective of BRCA1/2 mutation status. Due to the ability of the BUB1 inhibitor to sensitize TNBC to different classes of drugs (platinum, PARPi, microtubule depolarization inhibitors), this work strongly supports the role of BUB1 as a novel molecular target to improve chemoradiation efficacy in TNBC and provides a rationale for the clinical evaluation of BAY1816032 as a chemosensitizer and chemoradiosensitizer in TNBC.
Investigation of Uterine Fluid Extracellular Vesicles’ Proteomic Profiles Provides Novel Diagnostic Biomarkers of Bovine Endometritis
Authors: Piibor Johanna , Waldmann Andres , Prasadani Madhusha , Kavak Ants , Andronowska Aneta , Klein Claudia , Kodithuwakku Suranga , Fazeli Alireza
Published: May 2024

Cow uterine infections pose a challenge in dairy farming, resulting in reproductive disorders. Uterine fluid extracellular vesicles (UF-EVs) play a key role in cell-to-cell communication in the uterus, potentially holding the signs of aetiology for endometritis. We used mass spectrometry-based quantitative shotgun proteomics to compare UF-EV proteomic profiles in healthy cows (H), cows with subclinical (SE) or clinical endometritis (CLE) sampled at 28–35 days postpartum. Functional analysis was performed on embryo cultures with the exposure to different EV types. A total of 248 UF-EV proteins exhibited differential enrichment between the groups. Interestingly, in SE, EV protein signature suggests a slight suppression of inflammatory response compared to CLE-UF-EVs, clustering closer with healthy cows’ profile. Furthermore, CLE-UF-EVs proteomic profile highlighted pathways associated with cell apoptosis and active inflammation aimed at pathogen elimination. In SE-UF-EVs, the regulation of normal physiological status was aberrant, showing cell damage and endometrial repair at the same time. Serine peptidase HtrA1 (HTRA1) emerged as a potential biomarker for SE. Supplementation of CLE- and SE-derived UF-EVs reduced the embryo developmental rates and quality. Therefore, further research is warranted to elucidate the precise aetiology of SE in cattle, and HTRA1 should be further explored as a potential diagnostic biomarker.
Biomechanics Is Marching Forward to Become a Trustworthy and Indexed Journal
Authors: Hortobágyi Tibor
Published: May 2024

Biomechanics (ISSN 2673-7078) is an international, peer-reviewed, open access journal covering all aspects of biomechanics, which can be described as the application of principles and methods of mechanics to the quantitative study of biological systems [...]
Exploring the Impact of Affinity and Unpleasantness on Conditioned Pain Modulation among Healthy Individuals
Authors: Ibancos-Losada María del Rocío , Díaz-Fernández Ángeles , Cortés-Pérez Irene , Obrero-Gaitán Esteban , López-Moreno Virginia , Osuna-Pérez María Catalina
Published: May 2024

The variability of the Conditioned Pain Modulation (CPM) effect can be attributed to conditioning stimulus (CS) characteristics, such as intensity, duration, unpleasantness, or affinity. This study investigates the impact of affinity and unpleasantness variables on the CPM effect using two protocols (cold water and ischemia) in the same healthy individuals (n = 54). Additional variables were also examined for their potential influence on the CPM effect. The main results are as follows: (1) a higher level of affinity and a lower level of unpleasantness for the stimuli used resulted in a stronger CPM effect; (2) significant differences were observed in the extreme categories (high and low) of both variables, whereas the ‘indifferent’ group did not show a clear trend; (3) within-subject analysis demonstrated that affinity for the CS had a clear impact on the CPM effect; (4) no correlations were found between the CPM effect and the additional variables, except for the extraversion variable with the CPM effect of the ischemia protocol, and CS duration variable with CPM effect in the cold water protocol; and (5) only the affinity variable explained the CPM effect in both protocols in the multiple linear regression analysis. The affinity variable was found to influence the CPM effects significantly, indicating its important role in our perception and response to pain.
Behavioral Effects of the Mixture and the Single Compounds Carbendazim, Fipronil, and Sulfentrazone on Zebrafish (Danio rerio) Larvae
Authors: Gomes Samara da Silva , da Silva Jadson Freitas , Padilha Renata Meireles Oliveira , de Vasconcelos João Victor Alves , Negreiros Neto Luís Gomes de , Marrs James A. , Cadena Pabyton Gonçalves
Published: May 2024

Pesticides are often detected in freshwater, but their impact on the aquatic environment is commonly studied based on single compounds, underestimating the potential additive effects of these mixtures. Even at low concentrations, pesticides can negatively affect organisms, altering important behaviors that can have repercussions at the population level. This study used a multi-behavioral approach to evaluate the effects of zebrafish larvae exposure to carbendazim (C), fipronil (F), and sulfentrazone (S), individually and mixed. Five behavioral tests, thigmotaxis, touch sensitivity, optomotor response, bouncing ball test, and larval exploratory behavior, were performed to assess potential effects on anxiety, fear, and spatial and social interaction. Significant changes were observed in the performance of larvae exposed to all compounds and their mixtures. Among the single pesticides, exposure to S produced the most behavioral alterations, followed by F and C, respectively. A synergistic effect between the compounds was observed in the C + F group, which showed more behavioral effects than the groups exposed to pesticides individually. The use of behavioral tests to evaluate pesticide mixtures is important to standardize methods and associate behavioral changes with ecologically relevant events, thus creating a more realistic scenario for investigating the potential environmental impacts of these compounds.
Metabolome-Wide Mendelian Randomization Assessing the Causal Role of Serum and Cerebrospinal Metabolites in Traumatic Brain Injury
Authors: Duan Aojie , Qiu Youjia , Song Bingyi , Tao Yuchen , Wang Menghan , Yin Ziqian , Xie Minjia , Chen Zhouqing , Wang Zhong , Sun Xiaoou
Published: May 2024

Previous studies have identified metabolites as biomarkers or potential therapeutic targets for traumatic brain injury (TBI). However, the causal association between them remains unknown. Therefore, we investigated the causal effect of serum metabolites and cerebrospinal fluid (CSF) metabolites on TBI susceptibility through Mendelian randomization (MR). Genetic variants related to metabolites and TBI were extracted from a corresponding genome-wide association study (GWAS). Causal effects were estimated through the inverse variance weighted approach, supplemented by a weighted median, weight mode, and the MR–Egger test. In addition, sensitivity analyses were further performed to evaluate the stability of the MR results, including the MR–Egger intercept, leave-one-out analysis, Cochrane’s Q-test, and the MR-PRESSO global test. Metabolic pathway analysis was applied to uncover the underlying pathways of the significant metabolites in TBI. In blood metabolites, substances such as 4-acetaminophen sulfate and kynurenine showed positive links, whereas beta-hydroxyisovalerate and creatinine exhibited negative correlations. CSF metabolites such as N-formylanthranilic acid were positively related, while kynurenate showed negative associations. The metabolic pathway analysis highlighted the potential biological pathways involved in TBI. Of these 16 serum metabolites, 11 CSF metabolites and metabolic pathways may serve as useful circulating biomarkers in clinical screening and prevention, and may be candidate molecules for the exploration of mechanisms and drug targets.
Low Vitamin K Status in Patients with Psoriasis Vulgaris: A Pilot Study
Authors: Gheorghe Simona R. , Ilyés Tamás , Filip Gabriela A. , Dănescu Ana S. , Timiș Teodora L. , Orăsan Meda , Stamate Irina , Crăciun Alexandra M. , Silaghi Ciprian N.
Published: May 2024

Psoriasis vulgaris (PV) is a disease characterized by skin manifestations and systemic inflammation. There are no published studies to date on vitamin K status assessed by extrahepatic vitamin K-dependent proteins [e.g., osteocalcin (OC) and matrix Gla protein (MGP)] in patients with PV, even if vitamin K was found to promote wound contraction and decrease the healing time of the skin. Metabolic syndrome (MS), a comorbidity of PV, was found to influence vitamin K status, and vitamin D was found to be involved in the pathogenesis of PV. Therefore, our aim was to assess the status of vitamins K and D in subjects with PV. We enrolled 44 patients with PV and 44 age- and sex-matched subjects as a control group (CG), of which individuals with MS were designated the CG with MS subgroup. Furthermore, the PV patients were stratified into two subgroups: those with MS (n = 20) and those without MS (n = 24). In addition to the quantification of vitamin D and MGP in all subjects, the uncarboxylated OC/carboxylated OC (ucOC/cOC) ratio was also assessed as an inversely proportional marker of vitamin K status. We found an increased ucOC/cOC ratio in the PV group compared to CG but also a greater ucOC/cOC ratio in the PV with MS subgroup than in the CG with MS subgroup. MGP was decreased in the PV with MS subgroup compared to CG with MS subgroup. There was no difference in the vitamin D concentration between the groups. This is the first study to report decreased vitamin K status in patients with PV, independent of the presence of MS.
Narrative Review of the Safety of Using Pigs for Xenotransplantation: Characteristics and Diagnostic Methods of Vertical Transmissible Viruses
Authors: Kim Su-Jin , Moon Joonho
Published: May 2024

Amid the deepening imbalance in the supply and demand of allogeneic organs, xenotransplantation can be a practical alternative because it makes an unlimited supply of organs possible. However, to perform xenotransplantation on patients, the source animals to be used must be free from infectious agents. This requires the breeding of animals using assisted reproductive techniques, such as somatic cell nuclear transfer, embryo transfer, and cesarean section, without colostrum derived in designated pathogen-free (DPF) facilities. Most infectious agents can be removed from animals produced via these methods, but several viruses known to pass through the placenta are not easy to remove, even with these methods. Therefore, in this narrative review, we examine the characteristics of several viruses that are important to consider in xenotransplantation due to their ability to cross the placenta, and investigate how these viruses can be detected. This review is intended to help maintain DPF facilities by preventing animals infected with the virus from entering DPF facilities and to help select pigs suitable for xenotransplantation.
Joint Effects of Exercise and Ramadan Fasting on Telomere Length: Implications for Cellular Aging
Authors: Almuraikhy Shamma , Sellami Maha , Naja Khaled , Al-Amri Hadaia Saleh , Anwardeen Najeha , Aden Amina , Dömling Alexander , Elrayess Mohamed A.
Published: May 2024

Aging is a fundamental biological process that progressively impairs the functionality of the bodily systems, leading to an increased risk of diseases. Telomere length is one of the most often used biomarkers of aging. Recent research has focused on developing interventions to mitigate the effects of aging and improve the quality of life. The objective of this study was to investigate the combined effect of exercise and Ramadan fasting on telomere length. Twenty-nine young, non-obese, healthy females were randomized into two groups: the control group underwent a 4-week exercise training program, and the second group underwent a 4-week exercise training program while fasting during Ramadan. Blood samples were collected, and measurements of clinical traits, cytokines, oxidative stress, and telomere length were performed before and after intervention. Telomere length increased significantly from baseline in the exercise-while-fasting group, but showed no significant change in the exercise control group. This increase was accompanied by a reduction in TNF-α, among other cytokines. Additionally, a significant positive correlation was observed between the mean change in telomere length and HDL in the exercise-while-fasting group only. This study is the first to report an increase in telomere length after combining Ramadan fasting with training, suggesting that exercising while fasting may be an effective tool for slowing down the aging rate. Further studies using larger and more diverse cohorts are warranted.
Development of Recombinant PLC-Zeta Protein as a Therapeutic Intervention for the Clinical Treatment of Oocyte Activation Failure
Authors: Saleh Alaaeldin , Thanassoulas Angelos , Aliyev Elnur , Swann Karl , Naija Azza , Yalcin Huseyin C. , Lai F. Anthony , Nomikos Michail
Published: May 2024

The sperm-specific phospholipase C zeta (PLCζ) protein is widely considered as the predominant physiological stimulus for initiating the Ca2+ release responsible for oocyte activation during mammalian fertilization. The increasing number of genetic and clinical reports that directly link PLCζ defects and/or deficiencies with oocyte activation failure (OAF) necessitates the use of a powerful therapeutic intervention to overcome such cases of male factor infertility. Currently, in vitro fertilization (IVF) clinics treat OAF cases after intracytoplasmic sperm injection (ICSI) with Ca2+ ionophores. Despite their successful use, such chemical agents are unable to trigger the physiological pattern of Ca2+ oscillations. Moreover, the safety of these ionophores is not yet fully established. We have previously demonstrated that recombinant PLCζ protein can be successfully used to rescue failed oocyte activation, resulting in efficient blastocyst formation. Herein, we produced a maltose binding protein (MBP)-tagged recombinant human PLCζ protein capable of inducing Ca2+ oscillations in mouse oocytes similar to those observed at fertilization. Circular dichroism (CD) experiments revealed a stable, well-folded protein with a high helical content. Moreover, the recombinant protein could retain its enzymatic properties for at least up to 90 days after storage at −80 °C. Finally, a chick embryo model was employed and revealed that exposure of fertilized chicken eggs to MBP-PLCζ did not alter the embryonic viability when compared to the control, giving a first indication of its safety. Our data support the potential use of the MBP-PLCζ recombinant protein as an effective therapeutic tool but further studies are required prior to its use in a clinical setting.
ATP and Formyl Peptides Facilitate Chemoattractant Leukotriene-B4 Synthesis and Drive Calcium Fluxes, Which May Contribute to Neutrophil Swarming at Sites of Cell Damage and Pathogens Invasion
Authors: Golenkina Ekaterina A. , Viryasova Galina M. , Galkina Svetlana I. , Iakushkina Iuliia V. , Gaponova Tatjana V. , Romanova Yulia M. , Sud’ina Galina F.
Published: May 2024

Here, we demonstrate that human neutrophil interaction with the bacterium Salmonella typhimurium fuels leukotriene B4 synthesis induced by the chemoattractant fMLP. In this work, we found that extracellular ATP (eATP), the amount of which increases sharply during tissue damage, can effectively regulate fMLP-induced leukotriene B4 synthesis. The vector of influence strongly depends on the particular stage of sequential stimulation of neutrophils by bacteria and on the stage at which fMLP purinergic signaling occurs. Activation of 5-lipoxygenase (5-LOX), key enzyme of leukotriene biosynthesis, depends on an increase in the cytosolic concentration of Ca2+. We demonstrate that eATP treatment prior to fMLP, by markedly reducing the amplitude of the fMLP-induced Ca2+ transient jump, inhibits leukotriene synthesis. At the same time, when added with or shortly after fMLP, eATP effectively potentiates arachidonic acid metabolism, including by Ca2+ fluxes stimulation. Flufenamic acid, glibenclamide, and calmodulin antagonist R24571, all of which block calcium signaling in different ways, all suppressed 5-LOX product synthesis in our experimental model, indicating the dominance of calcium-mediated mechanisms in eATP regulatory potential. Investigation into the adhesive properties of neutrophils revealed the formation of cell clusters when adding fMLP to neutrophils exposed to the bacterium Salmonella typhimurium. eATP added simultaneously with fMLP supported neutrophil polarization and clustering. A cell-derived chemoattractant such as leukotriene B4 plays a crucial role in the recruitment of additional neutrophils to the foci of tissue damage or pathogen invasion, and eATP, through the dynamics of changes in [Ca2+]i, plays an important decisive role in fMLP-induced leukotrienes synthesis during neutrophil interactions with the bacterium Salmonella typhimurium.
The Efficacy of the Addition of tDCS and TENS to an Education and Exercise Program in Subjects with Knee Osteoarthritis: A Randomized Controlled Trial
Authors: Montilla-Herrador Joaquina , Lozano-Meca Jose , Lozano-Guadalajara Juan Vicente , Gacto-Sánchez Mariano
Published: May 2024

Knee osteoarthritis (KOA) has a significant impact on patients’ quality of life. This study aimed to assess the effectiveness of integrating transcranial direct current stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) into an education and exercise program with the aim of decreasing pain and improving physical function in KOA. A randomized controlled trial with 65 KOA patients was conducted. The subjects were assigned to one of the following three groups: education and active exercise plus (1) double active tDCS and TENS, (2) active tDCS and sham TENS, and (3) double sham tDCS and TENS. Sessions were conducted over a 20 min period, whilst data on pain, chronic pain clinical variables, and physical function were collected. Although all groups showed improvement in pain-related symptoms in the short and medium term, the addition of tDCS and/or TENS did not significantly enhance the benefits of the exercise and education program. These findings suggest that an education and active exercise program in the treatment of KOA has a positive effect on pain, with or without the addition of tDCS and/or TENS.
Combination of Neovestitol and Vestitol Modifies the Profile of Periodontitis-Related Subgingival Multispecies Biofilm
Authors: Macedo Tatiane Tiemi , Malavazi Larissa Matias , Vargas Gustavo Quilles , Gonçalves Francisco Jerfeson dos Santos , Gomes Aline Paim de Abreu Paulo , Bueno Manuela Rocha , Aguiar da Silva Lucas Daylor , Figueiredo Luciene Cristina , Bueno-Silva Bruno
Published: May 2024

The aim of this study was to evaluate the effect of the combination of neovestitol–vestitol (CNV) compounds obtained from Brazilian red propolis on the microbiological profile of a mature multispecies subgingival biofilm. The biofilm with 32 bacterial species associated with periodontitis was formed for seven days using a Calgary device. Treatment with CNV (1600, 800, 400, and 200 μg/mL), amoxicillin (54 μg/mL), and vehicle control was performed for 24 h on the last day of biofilm formation. Biofilm metabolic activity and DNA–DNA hybridization (checkerboard) assays were performed. The groups treated with CNV 1600 and amoxicillin reduced 25 and 13 species, respectively, compared to the control vehicle treatment (p ≤ 0.05); both reduced P. gingivalis, while only CNV reduced T. forsythia. When the data from the two treatments (CNV and AMOXI) were compared, a statistically significant difference was observed in 13 species, particularly members of Socransky’s orange complex. Our results showed that CNV at 1600 μg/mL showed the best results regarding the metabolic activity of mature biofilms and obtained a reduction in species associated with the disease, such as T. forsythia, showing a better reduction than amoxicillin. Therefore, CNV seems to be a promising alternative to eradicate biofilms and reduce their pathogenicity.
Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure–Activity Relationships
Authors: Singh Atamjit , Singh Karanvir , Kaur Kamaljit , Singh Amandeep , Sharma Aman , Kaur Kirandeep , Kaur Jaskirat , Kaur Gurleen , Kaur Uttam , Kaur Harsimran , Singh Prabhsimran , Bedi Preet Mohinder Singh
Published: May 2024

Breast cancer is the most common cancer among women. Currently, it poses a significant threat to the healthcare system due to the emerging resistance and toxicity of available drug candidates in clinical practice, thus generating an urgent need for the development of new potent and safer anti-breast cancer drug candidates. Coumarin (chromone-2-one) is an elite ring system widely distributed among natural products and possesses a broad range of pharmacological properties. The unique distribution and pharmacological efficacy of coumarins attract natural product hunters, resulting in the identification of numerous natural coumarins from different natural sources in the last three decades, especially those with anti-breast cancer properties. Inspired by this, numerous synthetic derivatives based on coumarins have been developed by medicinal chemists all around the globe, showing promising anti-breast cancer efficacy. This review is primarily focused on the development of coumarin-inspired anti-breast cancer agents in the last three decades, especially highlighting design strategies, mechanistic insights, and their structure–activity relationship. Natural coumarins having anti-breast cancer efficacy are also briefly highlighted. This review will act as a guideline for researchers and medicinal chemists in designing optimum coumarin-based potent and safer anti-breast cancer agents.
Aminolysis-Based Zwitterionic Immobilization on Polyethersulfone Membranes for Enhanced Hemocompatibility: Experimental, Computational, and Ex Vivo Investigations
Authors: Mollahosseini Arash , Bahig Jumanah , Shoker Ahmed , Abdelrasoul Amira
Published: May 2024

Dialysis membranes are not hemocompatible with human blood, as the patients are suffering from the blood–membrane interactions’ side effects. Zwitterionic structures have shown improved hemocompatibility; however, their complicated synthesis hinders their commercialization. The goal of the study is to achieve fast functionalization for carboxybetaine and sulfobetaine zwitterionic immobilization on PES membranes while comparing the stability and the targeted hemocompatibility. The chemical modification approach is based on an aminolysis reaction. Characterization, computational simulations, and clinical analysis were conducted to study the modified membranes. Atomic force microscopy (AFM) patterns showed a lower mean roughness for carboxybetaine-modified (6.3 nm) and sulfobetaine-modified (7.7 nm) membranes compared to the neat membrane (52.61 nm). The pore size of the membranes was reduced from values above 50 nm for the neat PES to values between 2 and 50 nm for zwitterionized membranes, using Brunauer–Emmett–Teller (BET) analysis. More hydrophilic surfaces led to a growth equilibrium water content (EWC) of nearly 6% for carboxybetaine and 10% for sulfobetaine-modified membranes. Differential scanning calorimetry (DSC) measurements were 12% and 16% stable water for carboxybetaine- and sulfobetaine-modified membranes, respectively. Sulfobetaine membranes showed better compatibility with blood with respect to C5a, IL-1a, and IL-6 biomarkers. Aminolysis-based zwitterionization was found to be suitable for the improvement of hemodialysis membranes. The approach introduced in this paper could be used to modify the current dialysis membranes with minimal change in the production facilities.
In Silico and In Vitro Evaluation of the Antifungal Activity of a New Chromone Derivative against Candida spp.
Authors: Araújo Gleycyelly Rodrigues , Costa Palloma Christine Queiroga Gomes da , Nogueira Paula Lima , Alves Danielle da Nóbrega , Ferreira Alana Rodrigues , da Silva Pablo R. , de Andrade Jéssica Cabral , de Sousa Natália F. , Loureiro Paulo Bruno Araujo , Sobral Marianna Vieira , Sousa Damião P. , Scotti Marcus Tullius , de Castro Ricardo Dias , Scotti Luciana
Published: May 2024

Candida species are frequently implicated in the development of both superficial and invasive fungal infections, which can impact vital organs. In the quest for novel strategies to combat fungal infections, there has been growing interest in exploring synthetic and semi-synthetic products, particularly chromone derivatives, renowned for their antimicrobial properties. In the analysis of the antifungal activity of the compound (E)-benzylidene-chroman-4-one against Candida, in silico and laboratory tests were performed to predict possible mechanisms of action pathways, and in vitro tests were performed to determine antifungal activity (MIC and MFC), to verify potential modes of action on the fungal cell membrane and wall, and to assess cytotoxicity in human keratinocytes. The tested compound exhibited predicted affinity for all fungal targets, with the highest predicted affinity observed for thymidylate synthase (−102.589 kJ/mol). MIC and CFM values ranged from 264.52 μM (62.5 μg/mL) to 4232.44 μM (1000 μg/mL). The antifungal effect likely occurs due to the action of the compound on the plasma membrane. Therefore, (E)-benzylidene-chroman-4-one showed fungicidal-like activity against Candida spp., possibly targeting the plasma membrane.