bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying Malware Packers through Multilayer Feature Engineering in Static Analysis
Authors: Alkhateeb Ehab , Ghorbani Ali , Habibi Lashkari Arash
Published: February 2024

This research addresses a critical need in the ongoing battle against malware, particularly in the form of obfuscated malware, which presents a formidable challenge in the realm of cybersecurity. Developing effective antivirus (AV) solutions capable of combating packed malware remains a crucial endeavor. Packed malicious programs employ encryption and advanced techniques to obfuscate their payloads, rendering them elusive to AV scanners and security analysts. The introduced research presents an innovative malware packer classifier specifically designed to adeptly identify packer families and detect unknown packers in real-world scenarios. To fortify packer identification performance, we have curated a meticulously crafted dataset comprising precisely packed samples, enabling comprehensive training and validation. Our approach employs a sophisticated feature engineering methodology, encompassing multiple layers of analysis to extract salient features used as input to the classifier. The proposed packer identifier demonstrates remarkable accuracy in distinguishing between known and unknown packers, while also ensuring operational efficiency. The results reveal an impressive accuracy rate of 99.60% in identifying known packers and 91% accuracy in detecting unknown packers. This novel research not only significantly advances the field of malware detection but also equips both cybersecurity practitioners and AV engines with a robust tool to effectively counter the persistent threat of packed malware.
Enhancing Pedestrian Tracking in Autonomous Vehicles by Using Advanced Deep Learning Techniques
Authors: Sukkar Majdi , Shukla Madhu , Kumar Dinesh , Gerogiannis Vassilis C. , Kanavos Andreas , Acharya Biswaranjan
Published: February 2024

Effective collision risk reduction in autonomous vehicles relies on robust and straightforward pedestrian tracking. Challenges posed by occlusion and switching scenarios significantly impede the reliability of pedestrian tracking. In the current study, we strive to enhance the reliability and also the efficacy of pedestrian tracking in complex scenarios. Particularly, we introduce a new pedestrian tracking algorithm that leverages both the YOLOv8 (You Only Look Once) object detector technique and the StrongSORT algorithm, which is an advanced deep learning multi-object tracking (MOT) method. Our findings demonstrate that StrongSORT, an enhanced version of the DeepSORT MOT algorithm, substantially improves tracking accuracy through meticulous hyperparameter tuning. Overall, the experimental results reveal that the proposed algorithm is an effective and efficient method for pedestrian tracking, particularly in complex scenarios encountered in the MOT16 and MOT17 datasets. The combined use of Yolov8 and StrongSORT contributes to enhanced tracking results, emphasizing the synergistic relationship between detection and tracking modules.
Location Analytics of Routine Occurrences (LARO) to Identify Locations with Regularly Occurring Events with a Case Study on Traffic Accidents
Authors: Wu Yanan , Yang Yalin , Yuan May
Published: February 2024

Conventional spatiotemporal methods take frequentist or density-based approaches to map event clusters over time. While these methods discern hotspots of varying continuity in space and time, their findings overlook locations of routine occurrences where the geographic context may contribute to the regularity of event occurrences. Hence, this research aims to recognize the routine occurrences of point events and relate site characteristics and situation dynamics around these locations to explain the regular occurrences. We developed an algorithm, Location Analytics of Routine Occurrences (LARO), to determine an appropriate temporal unit based on event periodicity, seek locations of routine occurrences, and geographically contextualize these locations through spatial association mining. We demonstrated LARO in a case study with over 250,000 reported traffic accidents from 2010 to 2018 in Dallas, Texas, United States. LARO identified three distinctive locations, each exhibiting varying frequencies of traffic accidents at each weekly hour. The findings indicated that locations with routine traffic accidents are surrounded by high densities of stores, restaurants, entertainment, and businesses. The timing of traffic accidents showed a strong relationship with human activities around these points of interest. Besides the LARO algorithm, this study contributes to the understanding of previously overlooked periodicity in traffic accidents, emphasizing the association between periodic human activities and the occurrence of street-level traffic accidents. The proposed LARO algorithm is applicable to occurrences of point-based events, such as crime incidents or animal sightings.
Effect of Microclimate on the Mass Emergence of Hypothenemus hampei in Coffee Grown under Shade of Trees and in Full Sun Exposure
Authors: García-Méndez Valentina , González-Gómez Rebeca , Toledo Jorge , Valle-Mora Javier Francisco , Barrera Juan F.
Published: February 2024

The rainfall regime has a significant impact on the microclimate and mass emergence of the coffee berry borer, Hypothenemus hampei (Coleoptera: Curculionidae) (CBB). Little is known, however, about the shade tree–microclimate–CBB mass emergence interaction. The objective of the present study was to compare the effect of microclimate on the mass emergence of CBB in a full sun-exposed plot with a plot shaded by trees. The experiment was conducted on a Robusta coffee farm in southern Chiapas, Mexico. In each plot, 18 traps baited with an alcohol mixture were installed to capture flying females, collecting caught individuals every hour from 8:00 to 18:00 h. A meteorological station recorded several microclimatic variables on 13 weekly sampling dates from February to May 2022. Significantly more CBB females were captured in the shaded plot. The largest number of CBB captures was recorded between 14:00 and 16:00 h for the shade plot and between 15:00 and 17:00 h for the sun-exposed plot. The mass emergence of CBB showed a positive association with precipitation, dew point, and wind speed samples and a negative association with maximum air temperature, average relative humidity, ultraviolet radiation, wind speed, and equilibrium moisture content. Our observations show that the relationship between shade trees, microclimate, and mass emergence of CBB is complex and that its study helps us to gain deeper insight into CBB bioecology and advance control techniques against this important pest.
Regeneration Abilities among Extant Animals Depend on Their Evolutionary History and Life Cycles
Authors: Alibardi Lorenzo
Published: February 2024

The present brief manuscript summarizes the main points supporting recently proposed hypotheses explaining the different distributions of regenerative capacity among invertebrates and vertebrates. The new hypotheses are based on the evolution of regeneration from marine animals to the terrestrial animals derived from them. These speculations suggest that animals that were initially capable of broad regeneration in the sea underwent epigenetic modifications during terrestrial adaptation that determined the loss of their regenerative abilities in sub-aerial conditions. These changes derived from the requirements of life on land that include variable dry and UV-exposed conditions. Terrestrial conditions do not allow for organ regeneration, especially in arthropods and amniotes. Nematodes, the other main metazoan group unable of regeneration, instead evolved eutely (a fixed number of body cells), a process which is incompatible with regeneration. All these changes involved gene loss, modification and new gene interactions within the genomes of terrestrial adapting animals that gave rise to sophisticated invertebrates and vertebrates adapted to living on land but with low cellular plasticity.
Media Forensic Considerations of the Usage of Artificial Intelligence Using the Example of DeepFake Detection
Authors: Siegel Dennis , Kraetzer Christian , Seidlitz Stefan , Dittmann Jana
Published: February 2024

In recent discussions in the European Parliament, the need for regulations for so-called high-risk artificial intelligence (AI) systems was identified, which are currently codified in the upcoming EU Artificial Intelligence Act (AIA) and approved by the European Parliament. The AIA is the first document to be turned into European Law. This initiative focuses on turning AI systems in decision support systems (human-in-the-loop and human-in-command), where the human operator remains in control of the system. While this supposedly solves accountability issues, it includes, on one hand, the necessary human–computer interaction as a potential new source of errors; on the other hand, it is potentially a very effective approach for decision interpretation and verification. This paper discusses the necessary requirements for high-risk AI systems once the AIA comes into force. Particular attention is paid to the opportunities and limitations that result from the decision support system and increasing the explainability of the system. This is illustrated using the example of the media forensic task of DeepFake detection.
Experimental Characterization of Screw-Extruded Carbon Fibre-Reinforced Polyamide: Design for Aeronautical Mould Preforms with Multiphysics Computational Guidance
Authors: Antolin-Urbaneja Juan Carlos , Vallejo Artola Haritz , Bellvert Rios Eduard , Gayoso Lopez Jorge , Hernández Vicente Jose Ignacio , Luengo Pizarro Ana Isabel
Published: February 2024

In this research work, the suitability of short carbon fibre-reinforced polyamide 6 in pellet form for printing an aeronautical mould preform with specific thermomechanical requirements is investigated. This research study is based on an extensive experimental characterization campaign, in which the principal mechanical properties of the printed material are determined. Furthermore, the temperature dependency of the material properties is characterized by testing samples at different temperatures for bead printing and stacking directions. Additionally, the thermal properties of the material are characterized, including the coefficient of thermal expansion. Moreover, the influence of printing machine parameters is evaluated by comparing the obtained tensile moduli and strengths of several manufactured samples at room temperature. The results show that the moduli and strengths can vary from 78% to 112% and from 55% to 87%, respectively. Based on a real case study of its aeronautical use and on the experimental data from the characterization stage, a new mould design is iteratively developed with multiphysics computational guidance, considering 3D printing features and limitations. Specific design drivers are identified from the observed material’s thermomechanical performance. The designed mould, whose mass is reduced around 90% in comparison to that of the original invar design, is numerically proven to fulfil thermal and mechanical requirements with a high performance.
INCONEL® Alloy Machining and Tool Wear Finite Element Analysis Assessment: An Extended Review
Authors: Pedroso André F. V. , Sebbe Naiara P. V. , Costa Rúben D. F. S. , Barbosa Marta L. S. , Sales-Contini Rita C. M. , Silva Francisco J. G. , Campilho Raul D. S. G. , de Jesus Abílio M. P.
Published: February 2024

Machining INCONEL® presents significant challenges in predicting its behaviour, and a comprehensive experimental assessment of its machinability is costly and unsustainable. Design of Experiments (DOE) can be conducted non-destructively through Finite Element Analysis (FEA). However, it is crucial to ascertain whether numerical and constitutive models can accurately predict INCONEL® machining. Therefore, a comprehensive review of FEA machining strategies is presented to systematically summarise and analyse the advancements in INCONEL® milling, turning, and drilling simulations through FEA from 2013 to 2023. Additionally, non-conventional manufacturing simulations are addressed. This review highlights the most recent modelling digital solutions, prospects, and limitations that researchers have proposed when tackling INCONEL® FEA machining. The genesis of this paper is owed to articles and books from diverse sources. Conducting simulations of INCONEL® machining through FEA can significantly enhance experimental analyses with the proper choice of damage and failure criteria. This approach not only enables a more precise calibration of parameters but also improves temperature (T) prediction during the machining process, accurate Tool Wear (TW) quantity and typology forecasts, and accurate surface quality assessment by evaluating Surface Roughness (SR) and the surface stress state. Additionally, it aids in making informed choices regarding the potential use of tool coatings.
Automatic Guided Vehicle Scheduling in Automated Container Terminals Based on a Hybrid Mode of Battery Swapping and Charging
Authors: Xiao Shichang , Huang Jinshan , Hu Hongtao , Gu Yuxin
Published: February 2024

Automatic guided vehicles (AGVs) in the horizontal area play a crucial role in determining the operational efficiency of automated container terminals (ACTs). To improve the operational efficiency of an ACT, it is essential to decrease the impact of battery capacity limitations on AGV scheduling. To address this problem, this paper introduces battery swapping and opportunity charging modes into the AGV system and proposes a new AGV scheduling problem considering the hybrid mode. Firstly, this study describes the AGV scheduling problem of the automated container terminals considering both loading and unloading tasks under the hybrid mode of battery swapping and charging. Thereafter, a mixed-integer programming model is established to minimize the sum of energy costs and delay costs. Secondly, an effective adaptive large neighborhood search algorithm is proposed to solve the problem, in which the initial solution construction, destroy operators, and repair operators are designed according to the hybrid mode. Finally, numerical experiments are conducted to analyze the effectiveness of the model and the optimization performance of the algorithm. The results demonstrate that the hybrid mode of battery swapping and charging can effectively reduce the number of battery swapping times and scheduling costs compared to the existing mode.
Development of an Automated Wooden Handle Packaging System with Integrated Counting Technology
Authors: Pereira Filipe , Magalhães Luís , Santos Adriano A. , da Silva António Ferreira , Antosz Katarzyna , Machado José
Published: February 2024

Manual counting and packaging processes often involve repetitive, error-prone tasks. Specifically, packaging wooden handles, utilized in gardening tools and cutlery, typically relies on labor-intensive methods with dimensions varying in diameter, length and mass. These variations complicate packaging, requiring precise counting and diverse handling solutions. This article introduces an automated counting structure tailored for a wide array of wooden handles manufactured by a company in northern Portugal. Employing standardized mechanical design methodologies, we delineate crucial stages encompassing the design, development, implementation and testing of this specialized counting equipment. The machine has been partially integrated into the management system of the company, taking into account future global integration according to the Industry 4.0 concept.
Integrated Profitability Evaluation for a Newsboy-Type Product in Own Brand Manufacturers
Authors: Su Rung-Hung , Tseng Tse-Min , Lin Chun
Published: February 2024

Effective inventory management depends on accurate estimates of product profitability to formulate ordering and manufacturing strategies. The achievable capacity index (ACI) is a simple yet efficient approach to measuring the profitability of newsboy-type products with normally distributed demand, wherein profitability is presented as the probability of achieving the target profit under the optimal ordering quantity. Unfortunately, the ACI is applicable only to retail stores with a single demand. In the current study, we addressed the issue of measuring the integrated profitability of newsboy-type products sold in multiple locations with independent demand levels, such as own-branding-and-manufacture (OBM) companies with multiple owned channels. We began by formulating profitability in accordance with multiple independent normal demands, and then developed an integrated ACI (IACI) to simplify expression. We also derived the statistical properties of the unbiased estimator to determine the true IACI in situations where demand patterns are unknown. Finally, we conducted hypothesis testing to determine whether the integrated profitability meets a stipulated minimum level. For convenience, we tabulated the critical values as a function of sample size, confidence level, the number of channels, and the stipulated minimum level. One can make decisions simply by estimating the IACI based on historical demand data from all channels and then looking up the critical value in the corresponding tables. Consequently, the proposed methods make it possible for OBM managers to address integrated profitability evaluation, which is effective in deciding the optimal timing to pull unprofitable items from the shelves by looking up generic tables. Furthermore, we also performed numerical and sensitivity analyses for a real-world case to illustrate the applicability and some managerial implications of the proposed scheme.
On Generalized Sehgal–Guseman-Like Contractions and Their Fixed-Point Results with Applications to Nonlinear Fractional Differential Equations and Boundary Value Problems for Homogeneous Transverse Bars
Authors: Din Muhammad , Ishtiaq Umar , Mukhtar Muzammil , Sessa Salvatore , Ghazwani Hassan Ali
Published: February 2024

The goal of this study is to describe the class of modified Sehgal–Guseman-like contraction mappings and set up some fixed-point results in S-metric spaces. The class of generalized Sehgal–Guseman-like contraction mappings contains enhancements of Banach contractions, Kannan contractions, Chatterjee contractions, Chatterjee-type contractions, quasi-contractions, Ćirić–Reich–Rus-type contractions, Hardy–Rogers-type contractions, Reich-type contractions, interpolative Kannan contractions, interpolative Chatterjee contractions, among others, with their generalizations in S-metric spaces. We offer significant examples to substantiate the reliability of our results. This study also establishes consequential fixed-point results and applies them to nonlinear fractional differential equations and the boundary value problem for homogeneous transverse bars. At the end of the manuscript, we present an important open problem.
A Study of Advancing Ultralow-Power 3D Integrated Circuits with TEI-LP Technology and AI-Enhanced PID Autotuning
Authors: Jeon Sangmin , Kwak Hyunseok , Lee Woojoo
Published: February 2024

The 3D integrated circuit (3D-IC) is garnering significant attention from academia and industry as a key technology leading the post-Moore era, offering new levels of efficiency, power, performance, and form-factor advantages to the semiconductor industry. However, thermal management in 3D-ICs presents a critical challenge that must be overcome to ensure prosperity for this technology. Unlike traditional thermal management solutions that perceive heat generation in 3D-ICs negatively and aim to eliminate it, this paper proposes, for the first time, a thermal management method that positively utilizes heat to achieve low-power operation in 3D-ICs. This approach is based on a novel discovery that circuits can reduce power consumption at higher temperatures by leveraging the temperature effect inversion (TEI) phenomenon in ultralow-voltage (ULV) operating circuits, a characteristic of low-power techniques (TEI-LP techniques). Along with a detailed explanation of this discovery, this paper introduces new thermal management technologies for practical application in 3D-ICs. Furthermore, to achieve optimal energy efficiency with the proposed technology, we develop a temperature controller essential for this purpose. The developed controller is a deep learning-based PID autotuner. This paper proves the theoretical validity of the AI control algorithm designed for this purpose and demonstrates the functional correctness and power-saving effectiveness of the developed controller through intensively conducted simulations.
Perirectal Abscess with Anterior Extension to the Extraperitoneum and Space of Retzius: A Case Report
Authors: Teng Hsiang , Wu Po-Hsien
Published: February 2024

Introduction—This report illuminates the distinctive features of a successfully managed Retzius space infection arising from a complex perirectal abscess. It adds novel insights to the scientific literature by addressing the rarity of such occurrences, highlighting the diagnostic complexities associated with extraperitoneal spread, and underscoring the crucial role of a nuanced understanding of anatomy in navigating clinical scenarios involving anorectal abscesses. Patient’s Main Concerns and Important Clinical Findings—A 68-year-old male presented with dizziness and diffuse lower abdominal pain, accompanied by intermittent perianal pain for one month. Regardless of an initial misdiagnosis as hemorrhoids, the patient presented sepsis status with fever, hypotension, and tachycardia upon admission. Clinical examinations, including a digital rectal examination, laboratory findings, and imaging studies, revealed a substantial perianal abscess extending into the space of Retzius. Primary Diagnoses, Interventions, and Outcomes—The primary diagnosis involved a heterogeneous fluid-filled perianal abscess extending into the Retzius space, confirmed by abdominal contrast-enhanced computed tomography (CT). Immediate initiation of broad-spectrum antibiotics and subsequent incision and drainage in the 8 o’clock region was performed. Post-operatively, the patient experienced rectal bleeding, necessitating suturing ligation. A follow-up CT scan revealed an extraperitoneal abscess around the bladder, leading to CT-guided drainage and identification of microbial pathogens. Antibiotic treatment with piperacillin-tazobactam was administered. With two weeks of antibiotics and post-operative care, the patient’s symptoms improved, and he was discharged with no signs of recurrence or complications. Conclusions—This case report emphasizes the importance of early consideration and identification of extraperitoneal abscesses for timely intervention. The complexity of anatomical planes in extraperitoneal spaces poses diagnostic challenges, necessitating a strategic treatment. The successful management of this case underscores the significance of a multidisciplinary approach, including prompt diagnosis, appropriate antibiotic therapy, and timely surgical interventions, ultimately contributing to improved outcomes in cases involving complex anorectal abscesses.
Evaluation of Surface Structure and Morphological Phenomena of Caucasian Virgin Hair with Atomic Force Microscopy
Authors: Krawczyk-Wołoszyn Karolina , Roczkowski Damian , Reich Adam
Published: February 2024

Background and Objectives: Atomic force microscopy (AFM) as a type of scanning microscopy (SPM), which has a resolution of fractions of a nanometer on the atomic scale, is widely used in materials science. To date, research using AFM in medicine has focused on neurodegenerative diseases, osteoporosis, cancer tumors, cell receptors, proteins and the DNA mismatch repair (MMR) system. Only a few small studies of hair imaging have been conducted, mostly in biotechnology or cosmetology. Thanks to the possibilities offered by AFM imaging, dermatologists can non-invasively assess the condition of hair and its possible disorders. Our goal was to capture images and microscopically analyze morphological changes in the surface of healthy hair. Materials and Methods: In this study, three to five hairs were collected from each person. Each hair was examined at nine locations (0.5; 1.0; 1.5; 2.0; 3.5; 4.5; 5.5; 6.5 and 7.0 cm from the root). At least 4 images (4–10 images) were taken at each of the 9 locations. A total of 496 photos were taken and analyzed. Metric measurements of hair scales, such as apparent length, width and scale step height, were taken. Results: This publication presents the changes occurring in hair during the natural delamination process. In addition, morphoological changes visualized on the surface of healthy hair (pitting, oval indentations, rod-shaped macro-fibrillar elements, globules, scratches, wavy edge) are presented. A quantitative analysis of the structures found was carried out. Conclusions: The findings of this study can be used in further research and work related to the subject of human hair. They can serve as a reference for research on scalp and hair diseases, as well as hair care.
A Decrease in Branched-Chain Amino Acids after a Competitive Male Professional Volleyball Game—A Metabolomic-Based Approach
Authors: Oliveira Taillan Martins , Ferreira Tathiany Jéssica , Franca Paula Albuquerque Penna , da Cruz Rudson Ribeiro , Bara-Filho Mauricio Gattás , Cahuê Fábio Luiz Candido , Valente Ana Paula , Pierucci Anna Paola Trindade Rocha
Published: February 2024

A competitive volleyball game is a highly metabolic and physically demanding event for professional players. This study aimed to investigate whether a single game at the end of a preseason promotes changes in the biochemical markers of physical exercise responses and the metabolomic profile of professional volleyball players. This cross-sectional study included 13 male Brazilian professional volleyball players. Food intake, body composition, heart rate, physical movement variables, and blood biochemical indicators were evaluated. For non-target metabolomic analysis, serum samples were subjected to 500 MHz Nuclear Magnetic Resonance. Data analysis showed no significant difference in the biochemical indicators after the game (p > 0.05). The level of metabolites present in the groups of the main components (β-hydroxybutyrate, arginine/lysine, isoleucine, leucine, and valine) had decreased after the game. However, formic acid and histidine levels increased. Among the compounds not part of the main components, hypoxanthine and tyrosine increased, whereas low-density lipoprotein and very low-density lipoprotein levels decreased. After the game, the metabolomic profiles of players showed significant negative variations in essential amino acids (leucine, valine, and isoleucine). These decreases might be influenced by athlete diet and reduced glycogen storage due to lower carbohydrate intake, potentially impacting serum-essential amino acid levels via oxidation in skeletal muscle. The study provides insights for developing metabolic compensation strategies in athletes.
Selective CW Laser Synthesis of MoS2 and Mixture of MoS2 and MoO2 from (NH4)2MoS4 Film
Authors: Hurley Noah , Bhandari Bhojraj , Kamau Steve , Gonzalez Rodriguez Roberto , Squires Brian , Kaul Anupama B. , Cui Jingbiao , Lin Yuankun
Published: February 2024

Very recently, the synthesis of 2D MoS2 and WS2 through pulsed laser-directed thermolysis can achieve wafer-scale and large-area structures, in ambient conditions. In this paper, we report the synthesis of MoS2 and MoS2 oxides from (NH4)2MoS4 film using a visible continuous-wave (CW) laser at 532 nm, instead of the infrared pulsed laser for the laser-directed thermolysis. The (NH4)2MoS4 film is prepared by dissolving its crystal powder in DI water, sonicating the solution, and dip-coating onto a glass slide. We observed a laser intensity threshold for the laser synthesis of MoS2, however, it occurred in a narrow laser intensity range. Above that range, a mixture of MoS2 and MoO2 is formed, which can be used for a memristor device, as demonstrated by other research groups. We did not observe a mixture of MoS2 and MoO3 in the laser thermolysis of (NH4)2MoS4. The laser synthesis of MoS2 in a line pattern is also achieved through laser scanning. Due to of the ease of CW beam steering and the fine control of laser intensities, this study can lead toward the CW laser-directed thermolysis of (NH4)2MoS4 film for the fast, non-vacuum, patternable, and wafer-scale synthesis of 2D MoS2.
Highly Sensitive Measurement of Horseradish Peroxidase Using Surface-Enhanced Raman Scattering of 2,3-Diaminophenazine
Authors: Evtushenko Evgeniy G. , Gavrilina Elizaveta S. , Vasilyeva Alexandra D. , Yurina Lyubov V. , Kurochkin Ilya N.
Published: February 2024

The development of various enzyme-linked immunosorbent assays (ELISAs) coupled with surface-enhanced Raman scattering (SERS) detection is a growing area in analytical chemistry due to their potentially high sensitivity. A SERS-based ELISA with horseradish peroxidase (HRP) as an enzymatic label, an o-phenylenediamine (oPD) substrate, and a 2,3-diaminophenazine (DAP) enzymatic product was one of the first examples of such a system. However, the full capabilities of this long-known approach have yet to be revealed. The current study addresses a previously unrecognized problem of SERS detection stage performance. Using silver nanoparticles and model mixtures of oPD and DAP, the effects of the pH, the concentration of the aggregating agent, and the particle surface chloride stabilizer were extensively evaluated. At the optimal mildly acidic pH of 3, a 0.93 to 1 M citrate buffer, and AgNPs stabilized with 20 mM chloride, a two orders of magnitude advantage in the limits of detection (LODs) for SERS compared to colorimetry was demonstrated for both DAP and HRP. The resulting LOD for HRP of 0.067 pmol/L (1.3 amol per assay) underscores that the developed approach is a highly sensitive technique. We suppose that this improved detection system could become a useful tool for the development of SERS-based ELISA protocols.
Characterization of Copper(II) and Zinc(II) Complexes of Peptides Mimicking the CuZnSOD Enzyme
Authors: Székely Enikő , Molnár Mariann , Lihi Norbert , Várnagy Katalin
Published: February 2024

Antimicrobial peptides are short cationic peptides that are present on biological surfaces susceptible to infection, and they play an important role in innate immunity. These peptides, like other compounds with antimicrobial activity, often have significant superoxide dismutase (SOD) activity. One direction of our research is the characterization of peptides modeling the CuZnSOD enzyme and the determination of their biological activity, and these results may contribute to the development of novel antimicrobial peptides. In the framework of this research, we have synthesized 10, 15, and 16-membered model peptides containing the amino acid sequence corresponding to the Cu(II) and Zn(II) binding sites of the CuZnSOD enzyme, namely the Zn(II)-binding HVGD sequence (80–83. fragments), the Cu(II)-binding sequence HVH (fragments 46–48), and the histidine (His63), which links the two metal ions as an imidazolate bridge: Ac-FHVHEGPHFN-NH2 (L1(10)), Ac-FHVHAGPHFNGGHVG-NH2 (L2(15)), and Ac-FHVHEGPHFNGGHVGD-NH2 (L3(16)). pH-potentiometric, UV-Vis-, and CD-spectroscopy studies of the Cu(II), Zn(II), and Cu(II)-Zn(II) mixed complexes of these peptides were performed, and the SOD activity of the complexes was determined. The binding sites preferred by Cu(II) and Zn(II) were identified by means of CD-spectroscopy. From the results obtained for these systems, it can be concluded that in equimolar solution, the –(NGG)HVGD- sequence of the peptides is the preferred binding site for copper(II) ion. However, in the presence of both metal ions, according to the native enzyme, the -HVGD- sequence offers the main binding site for Zn(II), while the majority of Cu(II) binds to the -FHVH- sequence. Based on the SOD activity assays, complexes of the 15- and 16-membered peptide have a significant SOD activity. Although this activity is smaller than that of the native CuZnSOD enzyme, the complexes showed better performance in the degradation of superoxide anion than other SOD mimics. Thus, the incorporation of specific amino acid sequences mimicking the CuZnSOD enzyme increases the efficiency of model systems in the catalytic decomposition of superoxide anion.
A Naphthoquinoline-Dione-Based Cu2+ Sensing Probe with Visible Color Change and Fluorescence Quenching in an Aqueous Organic Solution
Authors: Kumar Ashwani , Chae Pil Seok
Published: February 2024

Copper metal ions (Cu2+) are widely used in various industries, and their salts are used as supplementary components in agriculture and medicine. As this metal ion is associated with various health issues, it is necessary to detect and monitor it in environmental and biological samples. In the present report, we synthesized a naphthoquinoline-dione-based probe 1 containing three ester groups to investigate its ability to detect metal ions in an aqueous solution. Among various metal ions, probe 1 showed a vivid color change from yellow to colorless in the presence of Cu2+, as observed by the naked eye. The ratiometric method using the absorbance ratio (A413/A476) resulted in a limit of detection (LOD) of 1 µM for Cu2+. In addition, the intense yellow-green fluorescence was quenched upon the addition of Cu2+, resulting in a calculated LOD of 5 nM. Thus, probe 1 has the potential for dual response toward Cu2+ detection through color change and fluorescence quenching. 1H-NMR investigation and density functional theory (DFT) calculations indicate 1:1 binding of the metal ion to the small cavity of the probe comprising four functional groups: the carbonyl group of the amide (O), the amino group (N), and two t-butyl ester groups (O). When adsorbed onto various solid surfaces, such as cotton, silica, and filter paper, the probe showed effective detection of Cu2+ via fluorescence quenching. Probe 1 was also useful for Cu2+ sensing in environmental samples (sea and drain water) and biological samples (live HeLa cells).
Use of Novel Homochiral Thioureas Camphor Derived as Asymmetric Organocatalysts in the Stereoselective Formation of Glycosidic Bonds
Authors: López Mildred , Huelgas Gabriela , Sánchez Mario , Armenta Adalid , Mendoza Angel , Lozada-Ramírez José Daniel , Anaya de Parrodi Cecilia
Published: February 2024

We synthesized six new camphor-derived homochiral thioureas 1–6, from commercially available (1R)-(−)-camphorquinone. These new compounds 1–6 were evaluated as asymmetric organocatalysts in the stereoselective formation of glycosidic bonds, with 2,3,4,6-tetra-O-benzyl-D-glucopyranosyl and 2,3,4,6-tetra-O-benzyl-D-galactopyranosyl trichloroacetimidates as donors, and several alcohols as glycosyl acceptors, such as methanol, ethanol, 1-propanol, 1-butanol, 1-octanol, iso-propanol, tert-butanol, cyclohexanol, phenol, 1-naphtol, and 2-naphtol. Optimization of the asymmetric glycosylation reaction was achieved by modifying reaction conditions such as solvent, additive, loading of catalyst, temperature, and time of reaction. The best result was obtained with 2,3,4,6-tetra-O-benzyl-D-galactopyranosyl trichloroacetimidates, using 15 mol% of organocatalyst 1, in the presence of 2 equiv of MeOH in solvent-free conditions at room temperature for 1.5 h, affording the glycosidic compound in a 99% yield and 1:73 α:β stereoselectivity; under the same reaction conditions, without using a catalyst, the obtained stereoselectivity was 1:35 α:β. Computational calculations prior to the formation of the products were modeled, using density functional theory, M06-2X/6-31G(d,p) and M06-2X/6-311++G(2d,2p) methods. We observed that the preference for β glycoside formation, through a stereoselective inverted substitution, relies on steric effects and the formation of hydrogen bonds between thiourea 1 and methanol in the complex formed.
An Overview of Polymeric Nanoplatforms to Deliver Veterinary Antimicrobials
Authors: Zhou Yaxin , Guo Lihua , Dai Guonian , Li Bing , Bai Yubin , Wang Weiwei , Chen Shulin , Zhang Jiyu
Published: February 2024

There is an urgent need to find new solutions for the global dilemma of increasing antibiotic resistance in humans and animals. Modifying the performance of existing antibiotics using the nanocarrier drug delivery system (DDS) is a good option considering economic costs, labor costs, and time investment compared to the development of new antibiotics. Numerous studies on nanomedicine carriers that can be used for humans are available in the literature, but relatively few studies have been reported specifically for veterinary pharmaceutical products. Polymer-based nano-DDS are becoming a research hotspot in the pharmaceutical industry owing to their advantages, such as stability and modifiability. This review presents current research progress on polymer-based nanodelivery systems for veterinary antimicrobial drugs, focusing on the role of polymeric materials in enhancing drug performance. The use of polymer-based nanoformulations improves treatment compliance in livestock and companion animals, thereby reducing the workload of managers. Although promising advances have been made, many obstacles remain to be addressed before nanoformulations can be used in a clinical setting. Some crucial issues currently facing this field, including toxicity, quality control, and mass production, are discussed in this review. With the continuous optimization of nanotechnology, polymer-based DDS has shown its potential in reducing antibiotic resistance to veterinary medicines.
Nutritional Considerations of Irish Performance Dietitians and Nutritionists in Concussion Injury Management
Authors: Finnegan Emma , Daly Ed , Ryan Lisa
Published: February 2024

Sport-related concussion incidence has increased in many team-based sports, such as rugby, Gaelic (camogie, hurling, football), and hockey. Concussion disrupts athletes’ brain function, causing an “energy crisis” that requires energy and nutrient support to restore function and heal. Performance dietitians and nutritionists play a role in supporting athletes’ post-injury nutritional demands. This study aimed to investigate Irish performance dietitians’ and nutritionists’ knowledge and implementation of nutritional strategies to manage and support athletes’ recovery following concussion. In-depth, semi-structured interviews were conducted with seventeen (n = 17) Irish performance dietitians and nutritionists recruited from the Sport and Exercise Nutrition register and other sporting body networks across Ireland. Participants practised or had practised with amateur and/or professional athletes within the last ten years. All interviews and their transcripts were thematically analysed to extract relevant insights. These data provided valuable insights revealing performance dietitians and nutritionists: (1) their awareness of concussion events and (2) their use of nutritional supports for concussion management. Furthermore, the research highlighted their implementation of ‘novel nutritional protocols’ specifically designed to support and manage athletes’ concussion recovery. There was a clear contrast between participants who had an awareness and knowledge of the importance of nutrition for brain recovery after sport-related concussion(s) and those who did not. Participants presenting with a practical understanding mentioned re-emphasising certain foods and supplements they were already recommending to athletes in the event of a concussion. Performance dietitians and nutritionists were keeping up to date with nutrition research on concussions, but limited evidence has prevented them from implementing protocols in practice. Meanwhile, participants mentioned trialling/recommending nutritional protocols, such as carbohydrate reloading, reducing omega-6 intake, and acutely supplementing creatine, omega-3 fish oils high in Docosahexaenoic acid, and probiotics to support brain healing. Performance dietitians’ and nutritionists’ use of nutrition protocols with athletes following concussion was linked to their knowledge and the limited scientific evidence available. Nutrition implementation, therefore, may be overlooked or implemented with uncertainty, which could negatively affect athletes’ recovery following sports-related concussions.
Long-Term Changes to the Microbiome, Blood Lipid Profiles and IL-6 in Female and Male Swedish Patients in Response to Bariatric Roux-en-Y Gastric Bypass
Authors: Prykhodko Olena , Burleigh Stephen , Campanello Magnus , Iresjö Britt-Marie , Zilling Thomas , Ljungh Åsa , Smedh Ulrika , Hållenius Frida Fåk
Published: February 2024

Lipid metabolism dysregulation is a critical factor contributing to obesity. To counteract obesity-associated disorders, bariatric surgery is implemented as a very effective method. However, surgery such as Roux-en-Y gastric bypass (RYGB) is irreversible, resulting in life-long changes to the digestive tract. The aim of the present study was to elucidate changes in the fecal microbiota before and after RYGB in relation to blood lipid profiles and proinflammatory IL-6. Here, we studied the long-term effects, up to six years after the RYGB procedure, on 15 patients’ gut microbiomes and their post-surgery well-being, emphasizing the biological sex of the patients. The results showed improved health among the patients after surgery, which coincided with weight loss and improved lipid metabolism. Health changes were associated with decreased inflammation and significant alterations in the gut microbiome after surgery that differed between females and males. The Actinobacteriota phylum decreased in females and increased in males. Overall increases in the genera Prevotella, Paraprevotella, Gemella, Streptococcus, and Veillonella_A, and decreases in Bacteroides_H, Anaerostipes, Lachnoclostridium_B, Hydrogeniiclostridium, Lawsonibacter, Paludicola, and Rothia were observed. In conclusion, our findings indicate that there were long-term changes in the gut microbiota after RYGB, and shifts in the microbial taxa appeared to differ depending on sex, which should be investigated further in a larger cohort.
Rab11a Controls Cell Shape via C9orf72 Protein: Possible Relationships to Frontotemporal Dementia/Amyotrophic Lateral Sclerosis (FTDALS) Type 1
Authors: Fukatsu Shoya , Sashi Hinami , Shirai Remina , Takagi Norio , Oizumi Hiroaki , Yamamoto Masahiro , Ohbuchi Katsuya , Miyamoto Yuki , Yamauchi Junji
Published: February 2024

Abnormal nucleotide insertions of C9orf72, which forms a complex with Smith–Magenis syndrome chromosomal region candidate gene 8 (SMCR8) protein and WD repeat-containing protein 41 (WDR41) protein, are associated with an autosomal-dominant neurodegenerative frontotemporal dementia and/or amyotrophic lateral sclerosis type 1 (FTDALS1). The differentially expressed in normal and neoplastic cells (DENN) domain-containing C9orf72 and its complex with SMCR8 and WDR41 function as a guanine-nucleotide exchange factor for Rab GTP/GDP-binding proteins (Rab GEF, also called Rab activator). Among Rab proteins serving as major effectors, there exists Rab11a. However, it remains to be established which Rab protein is related to promoting or sustaining neuronal morphogenesis or homeostasis. In this study, we describe that the knockdown of Rab11a decreases the expression levels of neuronal differentiation marker proteins, as well as the elongation of neurite-like processes, using N1E-115 cells, a well-utilized neuronal differentiation model. Similar results were obtained in primary cortical neurons. In contrast, the knockdown of Rab11b, a Rab11a homolog, did not significantly affect their cell morphological changes. It is of note that treatment with hesperetin, a citrus flavonoid (also known as Vitamin P), recovered the neuronal morphological phenotypes induced by Rab11a knockdown. Also, the knockdown of Rab11a or Rab11b led to a decrease in glial marker expression levels and in morphological changes in FBD-102b cells, which serve as the oligodendroglial differentiation model. Rab11a is specifically involved in the regulation of neuronal morphological differentiation. The knockdown effect mimicking the loss of function of C9orf72 is reversed by treatment with hesperetin. These findings may reveal a clue for identifying one of the potential molecular and cellular phenotypes underlying FTDALS1.
Determining the Oxidation Mechanism through Radical Intermediates in Polysorbates 80 and 20 by Electron Paramagnetic Resonance Spectroscopy
Authors: Sutton Adam T. , Rustandi Richard R.
Published: February 2024

Polysorbates 20 and 80 (PS20 and PS80) are added to many commercial biologic and vaccine pharmaceuticals. It is commonly known that these polysorbates undergo a radical oxidation mechanism; however, the identity of these radical intermediates has not been clearly determined. Furthermore, PS20 and PS80 differ by the presence of a lauric acid instead of an oleic acid, respectively. The oxidation of PS80 is thought to be centered around the double bond of the oleic acid even though PS20 also undergoes oxidation, making the mechanism of oxidation unclear for PS20. Using commercial stocks of PS20 and PS80 alkyl (R•), alkoxyl (C-O•) and peroxyl (C-OO•) radicals were detected by electron paramagnetic resonance spectroscopy likely originating from radical-initiating species already present in the material. When dissolved in water, the peroxyl radicals (C-OO•) originally in the stocks were not detected but poly(ethylene oxide) radicals were. An oxidative pathway for polysorbates was suggested based on the radical species identified in the polysorbate stock material and solutions.
Immunotherapy Innovations in the Fight against Osteosarcoma: Emerging Strategies and Promising Progress
Authors: Cheng Shigao , Wang Huiyuan , Kang Xuejia , Zhang Hui
Published: February 2024

Immunosuppressive elements within the tumor microenvironment are the primary drivers of tumorigenesis and malignant advancement. The presence, as well as the crosstalk between myeloid-derived suppressor cells (MDSCs), osteosarcoma-associated macrophages (OS-Ms), regulatory T cells (Tregs), and endothelial cells (ECs) with osteosarcoma cells cause the poor prognosis of OS. In addition, the consequent immunosuppressive factors favor the loss of treatment potential. Nanoparticles offer a means to dynamically and locally manipulate immuno-nanoparticles, which present a promising strategy for transforming OS-TME. Additionally, chimeric antigen receptor (CAR) technology is effective in combating OS. This review summarizes the essential mechanisms of immunosuppressive cells in the OS-TME and the current immune-associated strategies. The last part highlights the limitations of existing therapies and offers insights into future research directions.