bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating Menstruation and Adverse Pregnancy Outcomes: Oxymoron or New Frontier? A Narrative Review
Authors: Tindal Kirstin , Cousins Fiona L. , Ellery Stacey J. , Palmer Kirsten R. , Gordon Adrienne , Filby Caitlin E. , Gargett Caroline E. , Vollenhoven Beverley , Davies-Tuck Miranda L.
Published: July 2024

Not discounting the important foetal or placental contribution, the endometrium is a key determinant of pregnancy outcomes. Given the inherently linked processes of menstruation, pregnancy and parturition with the endometrium, further understanding of menstruation will help to elucidate the maternal contribution to pregnancy. Endometrial health can be assessed via menstrual history and menstrual fluid, a cyclically shed, easily and non-invasively accessible biological sample that represents the distinct, heterogeneous composition of the endometrial environment. Menstrual fluid has been applied to the study of endometriosis, unexplained infertility and early pregnancy loss; however, it is yet to be examined regarding adverse pregnancy outcomes. These adverse outcomes, including preeclampsia, foetal growth restriction (FGR), spontaneous preterm birth and perinatal death (stillbirth and neonatal death), lay on a spectrum of severity and are often attributed to placental dysfunction. The source of this placental dysfunction is largely unknown and may be due to underlying endometrial abnormalities or endometrial interactions during placentation. We present existing evidence for the endometrial contribution to adverse pregnancy outcomes and propose that a more comprehensive understanding of menstruation can provide insight into the endometrial environment, offering great potential value as a diagnostic tool to assess pregnancy risk. As yet, this concept has hardly been explored.
Frequency and Risk Factors Associated with Prematurity: A Cohort Study in a Neonatal Intensive Care Unit
Authors: Barreto Maria Goretti Policarpo , Manso Maria Conceição , Barreto Renata Policarpo , Barreto Roberta Policarpo , Vasconcelos Lara Moreira Teles de , Silva Cláudia
Published: July 2024

Background/Objectives: Prematurity rates remain high and represent a challenge for the public health systems of any country, with a high impact on neonatal mortality. This study aimed to evaluate the frequency and environmental and maternal–fetal risk factors for premature birth in a cohort of parturient women, with their newborns monitored in a neonatal intensive care unit at a private reference hospital. Methods: A cohort was carried out between 2013 and 2018 among parturient women living in a capital city in the Northeast of Brazil whose newborns were admitted to the neonatal intensive care unit. This study was approved by the Research Ethics Committee of the University of Fortaleza. The information collected comprised data from both medical records and hydrosanitary data from maternal homes. Results: The prevalence of prematurity among live births (n = 9778) between 2013 and 2018 at this hospital was 23%. The frequency of prematurity among those eligible (n = 480) was 76.9%, and the frequency of eligible premature babies (n = 369) in relation to the total number of births in this period was 3.8%. In the multivariate analysis, the significant risk factors for prematurity were primigravida (RR = 1.104, 95%CI: 1.004–1.213) and hypertensive syndromes during pregnancy (RR = 1.262, 95%CI: 1.161–1.371), and the significant protective factor was the highest number of prenatal consultations (RR = 0.924, 95%CI: 0.901–0.947). Conclusions: This study contributes to providing greater visibility to prenatal care and the understanding of complications during pregnancy and childbirth care. These results indicate the need to implement public policies that promote improvements in the population’s living conditions and care for pregnant women to reduce premature births and, consequently, neonatal and infant mortality.
Atlantoaxial Instability in the Course of Rheumatoid Arthritis in Relation to Selected Parameters of Sagittal Balance
Authors: Wróblewski Robert , Mańczak Małgorzata , Gasik Robert
Published: July 2024

Background: Atlantoaxial instability is the most common cervical instability in patients with rheumatoid arthritis (RA). Its course may differ in different patients and may have different degrees of severity and symptoms. Methods: There are a number of studies on systemic factors associated with the development of this instability, but there are few publications in the scientific literature on the influence of biomechanical factors on the development of cervical instability. One of the areas that allows the study of biomechanical factors influencing spine pathologies is the analysis of sagittal balance using radiological parameters. The study of radiological parameters of sagittal balance has contributed to understanding the pathology of selected spine diseases and is currently an indispensable tool in planning surgical treatment. Results: The presented study, conducted on a group of RA patients with cervical instability, was performed to look for a relationship between C1–C2 instability and sagittal balance parameters. Conclusions: Among the examined selected parameters, a statistically relationship between C1–C2 instability and the Cobb angle C1–C7 and OD-HA parameters has been found. This confirms the need for further in-depth research on this areas.
Strain-Energy-Density Guided Design of Functionally Graded Beams
Authors: Luo Yunhua
Published: July 2024

Functionally graded materials (FGMs) are revolutionizing various industries with their customizable properties, a key advantage over traditional composites. The rise of voxel-based 3D printing has furthered the development of FGMs with complex microstructures. Despite these advances, current design methods for FGMs often use abstract mathematical functions with limited relevance to actual performance. Furthermore, conventional micromechanics models for the analysis of FGMs tend to oversimplify, leading to inaccuracies in effective property predictions. To address these fundamental deficiencies, this paper introduces new gradation functions for functionally graded beams (FGBs) based on bending strain energy density, coupled with a voxel-based design and analysis approach. For the first time, these new gradation functions directly relate to structural performance and have proven to be more effective than conventional ones in improving beam performance, particularly under complex bending moments influenced by various loading and boundary conditions. This study reveals the significant role of primary and secondary gradation indices in material composition and distribution, both along the beam axis and across sections. It identifies optimal combinations of these indices for enhanced FGB performance. This research not only fills gaps in FGB design and analysis but also opens possibilities for applying these concepts to other strain energy density types, like shearing and torsion, and to different structural components such as plates and shells.
Luteinizing Hormone-Releasing Hormone (LHRH)-Conjugated Cancer Drug Delivery from Magnetite Nanoparticle-Modified Microporous Poly-Di-Methyl-Siloxane (PDMS) Systems for the Targeted Treatment of Triple Negative Breast Cancer Cells
Authors: Eluu Stanley C. , Obayemi John D. , Yiporo Danyuo , Salifu Ali A. , Oko Augustine O. , Onwudiwe Killian , Aina Toyin , Oparah Josephine C. , Ezeala Chukwudi C. , Etinosa Precious O. , Osafo Sarah A. , Ugwu Malachy C. , Esimone Charles O. , Soboyejo Winston O.
Published: July 2024

This study presents LHRH conjugated drug delivery via a magnetite nanoparticle-modified microporous Poly-Di-Methyl-Siloxane (PDMS) system for the targeted suppression of triple-negative breast cancer cells. First, the MNP-modified PDMS devices are fabricated before loading with targeted and untargeted cancer drugs. The release kinetics from the devices are then studied before fitting the results to the Korsmeyer–Peppas model. Cell viability and cytotoxicity assessments are then presented using results from the Alamar blue assay. Apoptosis induction is then elucidated using flow cytometry. The in vitro drug release studies demonstrated a sustained and controlled release of unconjugated drugs (Prodigiosin and paclitaxel) and conjugated drugs [LHRH conjugated paclitaxel (PTX+LHRH) and LHRH-conjugated prodigiosin (PG+LHRH)] from the magnetite nanoparticle modified microporous PDMS devices for 30 days at 37 °C, 41 °C, and 44 °C. At 24, 48, 72, and 96 h, the groups loaded with conjugated drugs (PG+LHRH and PTX+LHRH) had a significantly higher (p < 0.05) percentage cell growth inhibition than the groups loaded with unconjugated drugs (PG and PTX). Additionally, throughout the study, the MNP+PDMS (without drug) group exhibited a steady rise in the percentage of cell growth inhibition. The flow cytometry results revealed a high incidence of early and late-stage apoptosis. The implications of the results are discussed for the development of biomedical devices for the localized and targeted release of cancer drugs that can prevent cancer recurrence following tumor resection.
Improving Robotic Milling Performance through Active Damping of Low-Frequency Structural Modes
Authors: Sahu Govind Narayan , Otto Andreas , Ihlenfeldt Steffen
Published: July 2024

Industrial robots are increasingly prevalent due to their large workspace and cost-effectiveness. However, their limited static and dynamic stiffness can lead to issues like mode coupling chatter and regenerative chatter in robotic milling processes, even at shallow cutting depths. These problems significantly impact performance, product quality, tool longevity, and can damage robot components. An active inertial actuator was deployed at the milling spindle to enhance dynamic stiffness and suppress low-frequency vibrations effectively. It was identified that the characteristics of the actuator change with its mounting orientation, a common scenario in robotic machining processes. This variation has not been reported in the literature. Our study includes the identification of model parameters for the actuator in both horizontal and vertical mountings. Additionally, the novelty of the present work lies in the specific design and implementation of compensation filters tailored for the active inertial actuator in both horizontal and vertical configurations. These filters address the unique challenges posed by low-frequency vibrations in robotic milling, offering significant improvements in dynamic stiffness and vibration suppression. Traditional model-based compensators were effective for vertical mounting, while pole-zero placement techniques with minimum phase systems were optimal for horizontal mounting. These compensators significantly enhanced dynamic stiffness, reducing maximum low-frequency robot structural modes by approximately 100% in horizontal mounting and approximately 214% in the vertical configuration of the actuator. This advancement promises to enhance industrial robot capabilities across diverse machining applications.
The Spatiotemporal Correlation between Human Activity Intensity and the Evolution of Ecosystem Service Value in the Songnen Plain, China
Authors: Guo Xinxin , Yang Yang , Zhang Yi , Kalantari Mohsen , Sun Jiali , Sun Weize , Guan Guofeng , Du Guoming
Published: July 2024

For the main grain-producing areas worldwide that balance multi-tasks of grain production, ecological protection, and economic development, quantitatively revealing the correlation between human activity intensity (HAI) and ecosystem service value (ESV) is conducive to formulating adapted ecological protection policies and promoting the coordinated development of the regional economy, society, and ecosystem. In this paper, we took the Songnen Plain of China as an example, employed a modified Equivalent Factor Method (integrating socio-economic data, the normalized difference vegetation index (NDVI), and land use data), and the HAI Assessment Model (based on the data of land use, night-time light, and population spatial distribution) to measure the ESV and HAI in the Songnen Plain of China for the years 1990, 1995, 2000, 2005, 2010, 2015, and 2020. We further applied the standard deviational ellipse method, the coupled coordination degree model, and the bivariate spatial autocorrelation models to reveal the spatiotemporal dynamics and correlation characteristics of ESV and HAI. The results showed the following: (1) Temporally, the ESV declined from 950.96 billion yuan in 1990 to 836.31 billion yuan in 2015, and then increased to 864.60 billion yuan in 2020, with the total loss attributed to the significant decline in the ESV of the natural ecosystem. Spatially, the ESV in the western and northeastern regions was relatively high, with a significant increase in the northeast. (2) HAI showed an upward trend from 1990 to 2020, while the high HAI levels gradually shrank after reaching the peak in 2000. Low HAI levels were mainly distributed in the northeast and southwest, aligning with the ecological space, while high HAI levels were distributed in the middle and southeast. (3) The interaction between ESV and HAI was marked by a negative correlation, transitioning from conflict to coordination. The spatial pattern of HAI and ESV showed H (HAI)-L (ESV) and L-H clustering, with H-H and L-L scattered distributions. This study contributes to providing a framework, methods, and suggestions for the sustainable planning and utilization of land and ecological protection in order to offer scientific references for the Songnen Plain, other major grain-producing areas, and related studies.
Exploring the Boundaries of Electrically Induced Bearing Damage in Grease-Lubricated Rolling Contacts
Authors: Janik Jack R. , Saha Sudip , Jackson Robert L. , Mills German
Published: July 2024

As public attention is increasingly drawn toward more sustainable transportation methods, the popularity of electric vehicles (EVs) as part of the solution is rapidly expanding. Operating conditions within EVs can be severe compared to standard combustion powertrains, and the risk of electrical arcing across mechanical surfaces from electric leakage currents incites additional concern. This study employed a series of electro-tribological tests utilizing various moving patterns to improve understanding of the driving conditions for electrically induced bearing damage (EIBD). Rolling ball-on-disk tests were performed with different polyurea-thickened greases. Rotational tests were initially run at various speeds and test durations, but electrical damage was limited. However, electrical damage was unmistakable when a reciprocating motion was used at different track lengths and speeds. These results suggest that the conditions associated with the track length, such as the number of directional changes and speed-dependent film thickness, play a considerable role in forming electrical damage. This work provides critical insights into the mechanisms of EIBD in EVs and other electrical systems. It highlights the importance of understanding the operational conditions that contribute to EIBD, which can lead to improved designs and maintenance practices, ultimately enhancing the efficiency and lifespan of these systems.
NO2-Sensitive SnO2 Nanoparticles Prepared Using a Freeze-Drying Method
Authors: Liu Lin , Zhao Jinbo , Jin Zhidong , Liu Fei , Zhao Dewen , Liu Zhengyang , Wang Fenglong , Wang Zhou , Liu Jiurong , Wu Lili
Published: July 2024

The n-type semiconductor SnO2 with a wide band gap (3.6 eV) is massively used in gas-sensitive materials, but pure SnO2 still suffers from a high operating temperature, low response, and tardy responding speed. To solve these problems, we prepared small-sized pure SnO2 using hydrothermal and freeze-drying methods (SnO2-FD) and compared it with SnO2 prepared using a normal drying method (SnO2-AD). The sensor of SnO2-FD had an ultra-high sensitivity to NO2 at 100 °C with excellent selectivity and humidity stability. The outstanding gas sensing properties are attributed to the modulation of energy band structure and the increased carrier concentration, making it more accessible for electron exchange with NO2. The excellent gas sensing properties of SnO2-FD indicate its tremendous potential as a NO2 sensor.
Hydroxyapatite-Filled Acrylonitrile–Butadiene Rubber Composites with Improved Cure Characteristics and Reduced Flammability
Authors: Maciejewska Magdalena , Rybiński Przemysław , Sowińska-Baranowska Anna
Published: July 2024

The goal of this work was to develop acrylonitrile–butadiene (NBR) elastomer composites filled with hydroxyapatite (HAP) characterized by improved cure characteristics and resistance to burning. Silane, i.e., (3-aminopropyl)-triethoxysilane, ionic liquid, i.e., 1-decyl-3-methylimidazolium bromide and surfactant, i.e., cetyltrimethylammonium bromide, were used to improve the filler’s dispersibility in the elastomer matrix and to reduce the time and temperature of vulcanization. The effects of HAP and dispersants on the cure characteristics, crosslink density and physico–chemical properties of NBR composites were explored. The additives used, especially the ionic liquid and surfactant, effectively improved the dispersion of HAP in the NBR matrix. The amount of HAP and the dispersant used strongly affected the cure characteristics and crosslink density of NBR. The optimal vulcanization time significantly increased with HAP content and was pronouncedly reduced when ionic liquid and surfactant were applied. In addition, ionic liquid and surfactant significantly lowered the onset vulcanization temperature and improved the crosslink density and hardness of the vulcanizates while impairing their elasticity. HAP and dispersants did not significantly affect the damping properties or chemical resistance of NBR vulcanizates. Above all, application of HAP considerably enhanced the resistance of vulcanizates to thermo-oxidative aging and reduced their flammability compared with the unfilled NBR.
Facilely Promoting the Concentration of Baicalin in Polylactic Acid Fiber for UV Shielding and Antibacterial Functions: A Customized and Sustainable Approach
Authors: Zhou Yuyang , Deng Peng , Chen Wei
Published: July 2024

There is a significant trend towards the integration of natural substances with bio-polymers for fully bio-based functional composites. Polylactic acid is regarded as a promising biodegradable polymer for replacing synthetic polymers. Differing from the case of natural fiber, the incompatibility of polylactic acid with bio-based molecules prevents it from being used to fabricate high-quality sustainable composites. This work presents a simultaneous ultraviolet shielding and antibacterial finishing process of polylactic acid combined with bioactive baicalin and an eco-friendly ester, which is highlighted for (a) the lack of synthetic chemicals involved in such process, (b) adsorption enhancement achieved at a mild temperature, and (c) marginal color change on treated polylactic acid. A response surface methodology was adopted to analyze the impacts of various factors on the baicalin quantity in polylactic acid, and to optimize the treatment condition. The uptake ratio of baicalin in polylactic acid was drastically promoted from 8.5 mg/g to 21.1 mg/g using methyl cinnamate. The response surface methodology based on a central composite design experiment indicated that the usage of baicalin was the most significant factor followed by methyl cinnamate and temperature. After optimization, a very faint color depth of 1.2 was apparent, but UPF 50+ and 92% bacterial reduction could be achieved. In all, the success in strengthening of the functionalities of polylactic acid extends the applications of polylactic acid products.
A Perovskite Material Screening and Performance Study Based on Asymmetric Convolutional Blocks
Authors: Ji Shumin , Zhang Yujie , Huang Yanyan , Yu Zhongwei , Zhou Yong , Lin Xiaogang
Published: July 2024

This study introduces an innovative method for identifying high-efficiency perovskite materials using an asymmetric convolution block (ACB). Our approach involves preprocessing extensive data on perovskite oxide materials and developing a precise predictive model. This system is designed to accurately predict key properties such as band gap and stability, thereby eliminating the reliance on traditional feature importance filtering. It exhibited outstanding performance, achieving an accuracy of 96.8% and a recall of 0.998 in classification tasks, and a coefficient of determination (R2) value of 0.993 with a mean squared error (MSE) of 0.004 in regression tasks. Notably, DyCoO3 and YVO3 were identified as promising candidates for photovoltaic applications due to their optimal band gaps. This efficient and precise method significantly advances the development of advanced materials for solar cells, providing a robust framework for rapid material screening.
Role of Quenching Temperature Selection in the Improvement of the Abrasive (Al2O3) Wear Resistance of Hybrid Multi-Component Cast Irons
Authors: Chabak Yuliia , Efremenko Vasily , Petryshynets Ivan , Golinskyi Michail , Shimizu Kazumichi , Efremenko Bohdan , Kudin Vadim , Azarkhov Alexander
Published: July 2024

In this paper, enhancing the tribological characteristics of novel cast metallic materials—hybrid multi-component cast irons—by applying a strengthening heat treatment is described. The experimental materials were the cast alloys of a nominal composition (5 wt.% W, 5 wt.% Mo, 5 wt.% V, 10 wt.% Cr, 2.5 wt.% Ti, Fe is a balance) supplemented with 0.3–1.1 wt.% C and 1.5–2.5 wt.% B (total of nine alloys). The heat treatment was oil-quenching followed by 200 °C tempering. The quench temperature (QT) varied in the range of 900–1200 °C, with a step of 50 °C (with a 2-h holding at QT). The correlation of the QT with microstructure and properties was estimated using microstructure/worn surface characterization, differential scanning calorimetry, hardness measurement, and three-body-abrasive wear testing (using Al2O3 particles). The as-cast alloys had a multi-phase structure consisting of primary and/or eutectic borocarbide M2(B,C)5, carboborides M(C,B), M7(C,B)3, M3(C,B), and the matrix (ferrite, martensite, pearlite/bainite) in different combinations and volume fractions. Generally, the increase in the quenching temperature resulted in a gradual increase in hardness (maximally to 66–67 HRC) and a decrease in the wear rate in most alloys. This was due to the change in the phase-structure state of the alloys under quenching, namely, the secondary carboboride precipitation, and replacing ferrite and pearlite/bainite with martensite. The wear rate was found to be inversely proportional to bulk hardness. The maximum wear resistance was attributed to QT = 1150–1200 °C, when the wear rate of the alloys was lowered by three to six times as compared to the as-cast state. With the QT increase, the difference in the wear rate of the alloys decreased by three times. The highest abrasive resistance was attributed to the alloys with 1.1 wt.% C, which had a 2.36–3.20 times lower wear rate as compared with that of the reference alloy (13 wt.% Cr cast iron, hardness of 66 HRC). The effects of carbon and boron on hardness and wear behavior are analyzed using the regression models developed according to the factorial design procedure. The wear mechanisms are discussed based on worn surface characterization.
Grain Structure and Texture Evolution in the Bottom Zone of Dissimilar Friction-Stir-Welded AA2024-T351 and AA7075-T651 Joints
Authors: Shou Haoge , Song Yaoyao , Zhang Chenghang , Zhang Pengfei , Zhao Wei , Zhu Xixia , Shi Peng , Xing Shule
Published: July 2024

High-strength dissimilar aluminum alloys are difficult to connect by fusion welding, while they can be successfully joined by friction stir welding (FSW). However, the asymmetrical deformation and heat input that occur during FSW result in the formation of a heterogeneous microstructure in their welded zone. In this work, the grain structure and texture evolution in the bottom zones of dissimilar FSW AA2024-T351 and AA7075-T651 joints at different welding speeds (feeding speeds) were quantitatively investigated. The results indicated that dynamic recrystallization occurs in the bottom zones of dissimilar FSW joints, and equiaxed grains with low grain sizes are formed at the welding speed of 60–240 mm/min. A high fraction of the recrystallized grains were generated in the bottom zones of the joints at a low welding speed, while a high fraction of the substructured grains are produced at a high welding speed. Different types of shear textures are produced in the bottom zones of the joints; the number fraction of shear texture types depends on different welding speeds. This study helps to understand the mechanism of microstructure homogenization in dissimilar FSW joints and provides a basis for further improving the microstructure of the welded zone for engineering applications.
Preparation and Characterization of Oxide Nanotubes on Titanium Surface for Use in Controlled Drug Release Systems
Authors: Osak Patrycja , Skwarek Sandra , Łukowiec Dariusz , Przeliorz Grzegorz , Łosiewicz Bożena
Published: July 2024

Preventing or treating infections at implantation sites where the risk of bacterial contamination is high requires the development of intelligent drug delivery systems. The objective of this work was to develop a production method and characterization of fourth-generation oxide nanotubes on titanium grade 4 surface as a potential drug carrier. This study focused on the anodizing process; physico-chemical characterization using FE-SEM, EDS, and FTIR; in vitro corrosion resistance in an artificial saliva solution; and determining the drug release kinetics of gentamicin sulfate using UV-VIS. The anodizing process was optimized to produce fourth-generation oxide nanotubes in a fluoride-free electrolyte, ensuring rapid growth and lack of order. Results showed that the length of the oxide nanotubes was inversely proportional to the anodizing voltage, with longer nanotubes formed at lower voltages. The nanotubes were shown to have a honeycomb structure with silver particles co-deposited on the surface for antibacterial properties and were capable of carrying and releasing the antibiotic gentamicin sulfate in a controlled manner, following Fick’s first law of diffusion. The corrosion resistance study demonstrates that the oxide nanotubes enhance the corrosion resistance of the titanium surface. The oxide nanotubes show promise in enhancing osseointegration and reducing post-implantation complications.
Prokaryotic Expression, Purification, and Biological Properties of a Novel Bioactive Protein (PFAP-1) from Pinctada fucata
Authors: Liu Peng , Li Wenyue , Liu Jianbing , Mo Xiaojian , Tang Jiaxing , Lin Jiang
Published: July 2024

Pinctada fucata meat is the main by-product of the pearl harvesting industry. It is rich in nutrition, containing a lot of protein and peptides, and holds significant value for both medicine and food. In this study, a new active protein was discovered and expressed heterogeneously through bioinformatics analysis. It was then identified using Western blot, molecular weight, and mass spectrometry. The antibacterial activity, hemolysis activity, antioxidant activity, and Angiotensin-Converting Enzyme II (ACE2) inhibitory activity were investigated. An unknown functional protein was screened through the Uniprot protein database, and its primary structure did not resemble existing proteins. It was an α-helical cationic polypeptide we named PFAP-1. The codon-optimized full-length PFAP-1 gene was synthesized and inserted into the prokaryotic expression vector pET-30a. The induced expression conditions were determined with a final isopropyl-β-d-thiogalactoside (IPTG) concentration of 0.2 mM, an induction temperature of 15 °C, and an induction time of 16 h. The recombinant PFAP-1 protein, with low endotoxin and sterility, was successfully prepared. The recombinant PFAP-1 protein exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro, and the diameter of the inhibition zone was 15.99 ± 0.02 mm. Its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 37.5 μg/mL and 150 μg/mL, respectively, and its hemolytic activity was low (11.21%) at the bactericidal concentration. The recombinant PFAP-1 protein significantly inhibited the formation of MRSA biofilm and eradicated MRSA biofilm. It also demonstrated potent 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) scavenging activity with a half-maximal inhibitory concentration (IC50) of 40.83 μg/mL. The IC50 of ACE2 inhibition was 5.66 μg/mL. Molecular docking results revealed that the optimal docking fraction of PFAP-1 protein and ACE2 protein was −267.78 kcal/mol, with a confidence level of 0.913. The stable binding complex was primarily formed through nine groups of hydrogen bonds, three groups of salt bridges, and numerous hydrophobic interactions. In conclusion, recombinant PFAP-1 can serve as a promising active protein in food, cosmetics, or medicine.
Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases
Authors: Zhang Mengli , Peng Zijing , Huang Zhenkuai , Fang Jiaqi , Li Xinhai , Qiu Xiaoting
Published: July 2024

Nonribosomal peptides (NRPs) are biosynthesized by nonribosomal peptide synthetases (NRPSs) and are widely distributed in both terrestrial and marine organisms. Many NRPs and their analogs are biologically active and serve as therapeutic agents. The adenylation (A) domain is a key catalytic domain that primarily controls the sequence of a product during the assembling of NRPs and thus plays a predominant role in the structural diversity of NRPs. Engineering of the A domain to alter substrate specificity is a potential strategy for obtaining novel NRPs for pharmaceutical studies. On the basis of introducing the catalytic mechanism and multiple functions of the A domains, this article systematically describes several representative NRPS engineering strategies targeting the A domain, including mutagenesis of substrate-specificity codes, substitution of condensation-adenylation bidomains, the entire A domain or its subdomains, domain insertion, and whole-module rearrangements.
Voltage-Gated K+ Channel Modulation by Marine Toxins: Pharmacological Innovations and Therapeutic Opportunities
Authors: Turcio Rita , Di Matteo Francesca , Capolupo Ilaria , Ciaglia Tania , Musella Simona , Di Chio Carla , Stagno Claudio , Campiglia Pietro , Bertamino Alessia , Ostacolo Carmine
Published: July 2024

Bioactive compounds are abundant in animals originating from marine ecosystems. Ion channels, which include sodium, potassium, calcium, and chloride, together with their numerous variants and subtypes, are the primary molecular targets of the latter. Based on their cellular targets, these venom compounds show a range of potencies and selectivity and may have some therapeutic properties. Due to their potential as medications to treat a range of (human) diseases, including pain, autoimmune disorders, and neurological diseases, marine molecules have been the focus of several studies over the last ten years. The aim of this review is on the various facets of marine (or marine-derived) molecules, ranging from structural characterization and discovery to pharmacology, culminating in the development of some “novel” candidate chemotherapeutic drugs that target potassium channels.
Neglect of Psychological Care for Children with Cerebral Palsy and Their Families and Its Impact on Their Occupational Engagement in Saudi Arabia
Authors: Elkholi Safaa M. , Awad Salwa S. , Alotaibi Madawi H.
Published: July 2024

Background and Objectives: Many children with (CP) and their families in Saudi Arabia struggle emotionally. Unfortunately, there have not been many studies conducted on how to help them with these challenges. This research aims to bring attention to this gap and to explore how a lack of proper mental health care might affect these children’s ability to participate in everyday activities. Materials and Methods: In this cross-sectional descriptive study, a survey was conducted between August and October 2023. A total of 300 parents of CP children from Saudi Arabia participated in the study. The impact of psychological care negligence on the occupational engagement of CP children and their families was assessed by designing a valid questionnaire. Results: A total of 300 parents of children with CP participated in this study. The majority of the sample, 71% of parents, said that their children did not receive any psychological care, and 59.7% of the participants said that their children did not even receive a referral to a psychologist. However, 60.3% of parents of children noticed a significant decline in the occupational performance of their children, and 65.7% predicted an improvement in their children’s performance with future psychological care. Conclusions: It is clear that there is a lack of awareness about the importance of mental health care for children with CP in Saudi Arabia. This lack of care hinders these children and their families’ occupational engagement and social participation.
Long-Term Survival after Coronary Artery Surgical Revascularization—Does Ambient Temperature Matter?
Authors: Urbanowicz Tomasz , Skotak Krzysztof , Bratkowski Jakub , Olasińska-Wiśniewska Anna , Filipiak Krzysztof J. , Michalak Michał , Grodecki Kajetan , Szczepański Krystian , Tykarski Andrzej , Krasińska Beata , Krasiński Zbigniew , Krasińska-Płachta Aleksandra , Jemielity Marek
Published: July 2024

Background and Objectives: The progression of global warming results in an increased exposure to extreme heat, leading to exaggeration of preexisting diseases and premature deaths. The aim of the study was to present possible risk factors for all-cause long-term mortality in patients who underwent surgical revascularization, including an assessment of the influence of ambient temperature exposure. Materials and Methods: Retrospective analysis included 153 (123 (80%) males and 30 (20%) females) patients who underwent off-pump revascularization and were followed for a median time of 2533 (1035–3250) days. The demographical, clinical data and ambient temperature exposure were taken into analysis for prediction of all-cause mortality. Individual exposure was calculated based on the place of habitation. Results: In the multivariate logistic regression model with backward stepwise elimination method, risk factors such as dyslipidaemia (p = 0.001), kidney disease (p = 0.005), age (p = 0.006), and body mass index (p = 0.007) were found to be significant for late mortality prediction. In addition to traditional factors, environmental characteristics, including tropical nights (p = 0.043), were revealed to be significant. Conclusions: High night-time ambient temperatures known as tropical nights may be regarded as additional long-term mortality risk factor after surgical revascularization.
Enhancing Bystander Intervention: Insights from the Utstein Analysis of Out-of-Hospital Cardiac Arrests in Slovenia
Authors: Petravić Luka , Miklič Rok , Burger Evgenija , Keše Urša , Kulovec Domen , Poljanšek Eva , Tomšič Gašper , Pintarič Tilen , Lopes Miguel Faria , Brezovnik Miha , Strnad Matej
Published: July 2024

Background and Objectives: Out-of-hospital cardiac arrest (OHCA) and survival is a pressing matter all around the world. Despite years of research and great strides and advancements, survival remains alarmingly low. The aim of this study was to measure the survival and characteristics of patients having an OHCA in Slovenia, with an in-depth look at how the bystanders affect the return of spontaneous circulation (ROSC) and survival of OHCA. Materials and Methods: In this observational cross-sectional prospective study, we enrolled patients between 1 September 2022 and 30 November 2022, with a follow-up period of 1 month. All OHCAs attended by the emergency medical services were included. Data were collected and analyzed according to the Utstein 2015 reporting template. Independent predictors of ROSC and 30-day survival or survival were explored using ridge regression. Results: ROSC was achieved in 41% of cases where resuscitation was attempted. The overall 30-day survival rate where resuscitation was attempted was 14%. In 13% of all cases where resuscitation was attempted, patients had a favorable neurological outcome. Using our prediction model, we found that defibrillation under 20 min and ventricular fibrillation as an initial rhythm improves survival, whilst no defibrillation and bystander full cardiopulmonary resuscitation negatively predicted survival. Conclusions: Slovenia has OHCA 30-day survival comparable to the rest of the European Union. The favorable neurological outcome is high. Our data show that bystanders do not significantly improve survival. This represents an untapped potential of general public education in cardiopulmonary resuscitation and automatic external defibrillator use. Following good practices from abroad and improving layperson CPR knowledge could further improve OHCA survival.
Safety and Early Return to Sports for Early ACL Reconstruction in Young Athletes: A Retrospective Study
Authors: Yamanashi Yuki , Mutsuzaki Hirotaka , Kawashima Tatsuhiro , Ikeda Kotaro , Deie Masataka , Kinugasa Tomonori
Published: July 2024

Background and Objectives: Although previous reports have shown that early anterior cruciate ligament (ACL) reconstruction is associated with an increased risk of stiffness, recommendations for delayed surgery are based on outdated literature. The advent of arthroscopic surgery and accelerated rehabilitation protocols warrants a reexamination of the optimal surgical timing. The purpose of this study was to investigate complications during early ACL reconstruction after injury in young athletes. Materials and Methods: A total of 87 patients (27 males and 60 females) were included in this study. Patients who underwent anatomic ACL reconstruction using hamstring autografts were evaluated. Patients under 25 years of age with a Tegner activity score greater than 6 were included and classified into three groups according to the time from injury to surgical treatment: one week from injury to surgery (early group), three to six weeks from injury to surgery (normal group), and three to six months from injury to surgery (delayed group). We evaluated the rates of various complications such as graft rupture, contralateral injury, the need for manipulation for loss of ROM, infection, and fracture around the knee up to 2 years postoperatively. In addition, we investigated postoperative muscle strength, Lysholm score, Tegner activity score, and period of the return to sport from injury. Results: Patients in the delayed group were younger than those in the other groups (p = 0.009). Patients in the early group had a lower range of motion than those in the other groups preoperationly. However, the 1-month postoperative range of motion was comparable between groups. Patients in the early group had greater postoperative Tegner activity scores than those in the other groups. The period of return to sport from injury in the delayed group was longer than in the other groups. There were no statistically significant differences in the postoperative complication rate, muscle strength, or Lysholm score. Conclusions: ACL reconstruction performed 1 week from injury to surgery in young athletic patients indicated the rate of complications were not significantly different among the groups. Early ACL reconstruction with no postoperative complications may be related to early return to sports and a high level of sports.
Improving Resistance of Mango to Colletotrichum gloeosporioides by Activating Reactive Oxygen Species and Phenylpropane Metabolism of Bacillus amyloliquefaciens GSBa-1
Authors: Li Wenya , Chen Hua , Cheng Jianhu , Zhang Min , Xu Yan , Wang Lihua , Zhao Xueqiao , Zhang Jinyao , Liu Bangdi , Sun Jing
Published: July 2024

This study aimed to explore the effects of Bacillus amyloliquefaciens GSBa-1 treatment on anthracnose disease resistance and the metabolism of reactive oxygen species (ROS) and phenylpropanoids in mangoes during storage. Mangoes were soaked in a solution containing 1 × 108 CFU/mL of B. amyloliquefaciens GSBa-1. The anthracnose disease incidence, disease index, respiration intensity, ethylene release, reactive oxygen species content, and the activities of related metabolic enzymes, phenylpropanoid-related metabolic enzymes, and phenolic acids in the skin and pulp of mangoes were investigated under normal temperature storage conditions. The results showed that the antagonistic bacterial treatment (ABT) did not significantly inhibit the growth of Colletotrichum gloeosporioides in vitro. However, it significantly reduced the incidence of mango anthracnose disease when applied to the mango peel. ABT enhanced the latent resistance of mango to anthracnose disease by activating its reactive oxygen and phenylpropanoid metabolism. It maintained higher levels of ROS production and elimination in the peel. Moreover, it rapidly activated manganese superoxide dismutase, induced the accumulation of H2O2, and enhanced the activity of manganese superoxide dismutase, catalase, ascorbate peroxidase, and peroxidase in the mango peel. Furthermore, ABT activated phenylalanine ammonia-lyase, cinnamic acid-4-hydroxylase, 4-coumaroyl-CoA ligase, and cinnamyl alcohol dehydrogenase in the mango peel and pulp, promoting the accumulation of antifungal phenolic acids such as gallic acid, catechins, and ellagic acid. Bacillus amyloliquefaciens GSBa-1 may be a potent inhibitor of mango anthracnose, primarily enhancing the resistance of mangoes to anthracnose by synergistically activating ROS in the peel and phenylpropanoid metabolism in the pulp, thereby reducing the incidence of anthracnose effectively.
Wild Vitis Species as Stilbenes Sources: Cane Extracts and Their Antibacterial Activity against Listeria monocytogenes
Authors: Hatem Okba , Steinbach Anita , Schneider György , Röckel Franco , Kőrösi László
Published: July 2024

Grapevines (Vitis spp.) produce several valuable polyphenol-type secondary metabolites including various stilbenoids. Although the potential application of stilbenes may offer alternative solutions to food safety or health challenges, only little information is available on their antibacterial activity against foodborne pathogens. In this work, high-performance liquid chromatography was used to analyze the stilbenoid profile of various wild Vitis species, including V. amurensis, V. davidii, V. pentagona, and V. romanetii, selected from the gene bank for grapes at the University of Pécs, Hungary. We found that the stilbene profile of cane extracts is strongly genotype-dependent, showing the predominant presence of ε-viniferin with a wide concentration range ≈ 320–3870 µg/g dry weight. A novel yet simple and efficient extraction procedure was developed and applied for the first time on grape canes, resulting in ε-viniferin-rich crude extracts that were tested against Listeria monocytogenes, an important foodborne pathogen. After 24 h exposure, V. pentagona and V. amurensis crude extracts completely eliminated the bacteria at a minimum bactericidal concentration of 42.3 µg/mL and 39.2 µg/mL of ε-viniferin, respectively. On the other hand, V. romanetii extract with 7.8 µg/mL of ε-viniferin resulted in 4 log reduction in the viable bacterial cells, while V. davidii extract with 1.4 µg/mL of ε-viniferin did not show significant antibacterial activity. These findings indicate that the ε-viniferin content was directly responsible for the antibacterial effect of cane extract. However, pure ε-viniferin (purity > 95%) required a higher concentration (188 µg/mL) to eradicate the bacteria under the same conditions, suggesting the presence of other antibacterial compounds in the cane extracts. Investigating the onset time of the bactericidal action was conducted through a kinetic experiment, and results showed that the reduction in living bacterial number started after 2 h; however, the bactericidal action demanded 24 h of exposure. Our results revealed that the canes of V. pentagona and V. amurensis species are a crucial bio-source of an important stilbene with antimicrobial activity and health benefits.
Advanced Application of Polymer Nanocarriers in Delivery of Active Ingredients from Traditional Chinese Medicines
Authors: Zhai Zhiyuan , Niu Jianda , Xu Liguo , Xu Jinbao
Published: July 2024

Active ingredients from Traditional Chinese Medicines (TCMs) have been a cornerstone of healthcare for millennia, offering a rich source of bioactive compounds with therapeutic potential. However, the clinical application of TCMs is often limited by challenges such as poor solubility, low bioavailability, and variable pharmacokinetics. To address these issues, the development of advanced polymer nanocarriers has emerged as a promising strategy for the delivery of TCMs. This review focuses on the introduction of common active ingredients from TCMs and the recent advancements in the design and application of polymer nanocarriers for enhancing the efficacy and safety of TCMs. We begin by discussing the unique properties of TCMs and the inherent challenges associated with their delivery. We then delve into the types of polymeric nanocarriers, including polymer micelles, polymer vesicles, polymer hydrogels, and polymer drug conjugates, highlighting their application in the delivery of active ingredients from TCMs. The main body of the review presents a comprehensive analysis of the state-of-the-art nanocarrier systems and introduces the impact of these nanocarriers on the solubility, stability, and bioavailability of TCM components. On the basis of this, we provide an outlook on the future directions of polymer nanocarriers in TCM delivery. This review underscores the transformative potential of polymer nanocarriers in revolutionizing TCM delivery, offering a pathway to harness the full therapeutic potential of TCMs while ensuring safety and efficacy in a modern medical context.
Mechanism of Action of Dihydroquercetin in the Prevention and Therapy of Experimental Liver Injury
Authors: Wei Hewei , Zhao Ting , Liu Xinglong , Ding Qiteng , Yang Junran , Bi Xiaoyu , Cheng Zhiqiang , Ding Chuanbo , Liu Wencong
Published: July 2024

Liver disease is a global health problem that affects the well-being of tens of thousands of people. Dihydroquercetin (DHQ) is a flavonoid compound derived from various plants. Furthermore, DHQ has shown excellent activity in the prevention and treatment of liver injury, such as the inhibition of hepatocellular carcinoma cell proliferation after administration, the normalization of oxidative indices (like SOD, GSH) in this tissue, and the down-regulation of pro-inflammatory molecules (such as IL-6 and TNF-α). DHQ also exerts its therapeutic effects by affecting molecular pathways such as NF-κB and Nrf2. This paper discusses the latest research progress of DHQ in the treatment of various liver diseases (including viral liver injury, drug liver injury, alcoholic liver injury, non-alcoholic liver injury, fatty liver injury, and immune liver injury). It explores how to optimize the application of DHQ to improve its effectiveness in treating liver diseases, which is valuable for preparing potential therapeutic drugs for human liver diseases in conjunction with DHQ.
Recent Development of Fluoroquinolone Derivatives as Anticancer Agents
Authors: Nowakowska Justyna , Radomska Dominika , Czarnomysy Robert , Marciniec Krzysztof
Published: July 2024

Cancer is the second leading cause of death in the world following cardiovascular disease. Its treatment, including radiation therapy and surgical removal of the tumour, is based on pharmacotherapy, which prompts a constant search for new and more effective drugs. There are high costs associated with designing, synthesising, and marketing new substances. Drug repositioning is an attractive solution. Fluoroquinolones make up a group of synthetic antibiotics with a broad spectrum of activity in bacterial diseases. Moreover, those compounds are of particular interest to researchers as a result of reports of their antiproliferative effects on the cells of the most lethal cancers. This article presents the current progress in the development of new fluoroquinolone derivatives with potential anticancer and cytotoxic activity, as well as structure–activity relationships, along with possible directions for further development.