bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Dune Reconstruction and Beach Nourishment to Mitigate Coastal Erosion of the Ebro Delta (Spain)
Authors: Costa Giuseppe Pio , Marino Massimiliano , Cáceres Iván , Musumeci Rosaria Ester
Published: October 2023

Coastal areas facing increasing erosion are resorting to sand displacement strategies to mitigate the erosive impact, which is exacerbated by climate change. In the face of climate change, coastal managers are more frequently resorting to sand displacement strategies to recover eroding coastlines. These vulnerable coastal zones require innovative approaches to minimize the need for frequent sand replenishment, extend their effectiveness and lower their maintenance expenses. This study undertakes a comparison of four primary nourishment strategies—a conventional uniform nourishment technique and the placement of a single sand dune evaluated at three different positions—in contrast to a scenario where no intervention is carried out. The investigation employs the XBeach numerical model to assess the outcomes of these diverse strategies under both low- and high-energetic storm conditions. The case study is a degraded coastal beach in the Ebro Delta (Spain). The results reveal a significant decrease in erosion when the dune is positioned closest to the shoreline. However, this erosion mitigation effect diminishes as the dune is situated further inland. Conversely, the sand nourishment measure exhibits minimal fluctuations in the volume of eroded sand when compared to the scenario with no intervention.
Magnetic Gradient Tensor Positioning Method Implemented on an Autonomous Underwater Vehicle Platform
Authors: Zeng Fanzong , Zhang Xueting , Liu Jingbiao , Li Hao , Zhu Zhengjing , Zhang Shihe
Published: October 2023

Underwater magnetic surveying serves as the fundamental prerequisite for detecting sensitive underwater targets and magnetically susceptible submerged objects. However, when utilizing magnetic gradient tensor measurements for underwater positioning, the stability of the measurement apparatus can be significantly affected by hydrodynamic disturbances in the underwater environment, thereby having a substantial impact on data quality. Autonomous Underwater Vehicles (AUV) are unmanned underwater robots designed to independently perform various tasks and operations in underwater environments. In order to ensure the quality of data collection, this paper proposes a structure utilizing an Autonomous Underwater Vehicles platform equipped with a three-component magnetic gradiometer. This structure employs second-order tensor positioning algorithms and vertical gradient positioning algorithms, coupled with the Autonomous Underwater Vehicles’s inherent vertical profile motion, to effectively achieve the precise positioning of underwater cables. Simulation results indicate that, in the absence of geomagnetic background noise, both horizontal and vertical structures yield favorable positioning results. However, when introducing background noise of 40,000 nT, the horizontal structure exhibits larger positioning errors, whereas the vertical structure demonstrates smaller errors. Experimental results show that in near-field scenarios, both structures achieve relatively similar positioning accuracy. Nevertheless, under identical distances in the far field, the vertical structure reduces errors by a minimum of 30.78% compared to the horizontal structure, thereby confirming the feasibility of integrating magnetic gradient tensor measurement structures with Autonomous Underwater Vehicles platforms.
From Saccharomyces cerevisiae to Ethanol: Unlocking the Power of Evolutionary Engineering in Metabolic Engineering Applications
Authors: Topaloğlu Alican , Esen Ömer , Turanlı-Yıldız Burcu , Arslan Mevlüt , Çakar Zeynep Petek
Published: October 2023

Increased human population and the rapid decline of fossil fuels resulted in a global tendency to look for alternative fuel sources. Environmental concerns about fossil fuel combustion led to a sharp move towards renewable and environmentally friendly biofuels. Ethanol has been the primary fossil fuel alternative due to its low carbon emission rates, high octane content and comparatively facile microbial production processes. In parallel to the increased use of bioethanol in various fields such as transportation, heating and power generation, improvements in ethanol production processes turned out to be a global hot topic. Ethanol is by far the leading yeast output amongst a broad spectrum of bio-based industries. Thus, as a well-known platform microorganism and native ethanol producer, baker’s yeast Saccharomyces cerevisiae has been the primary subject of interest for both academic and industrial perspectives in terms of enhanced ethanol production processes. Metabolic engineering strategies have been primarily adopted for direct manipulation of genes of interest responsible in mainstreams of ethanol metabolism. To overcome limitations of rational metabolic engineering, an alternative bottom-up strategy called inverse metabolic engineering has been widely used. In this context, evolutionary engineering, also known as adaptive laboratory evolution (ALE), which is based on random mutagenesis and systematic selection, is a powerful strategy to improve bioethanol production of S. cerevisiae. In this review, we focus on key examples of metabolic and evolutionary engineering for improved first- and second-generation S. cerevisiae bioethanol production processes. We delve into the current state of the field and show that metabolic and evolutionary engineering strategies are intertwined and many metabolically engineered strains for bioethanol production can be further improved by powerful evolutionary engineering strategies. We also discuss potential future directions that involve recent advancements in directed genome evolution, including CRISPR-Cas9 technology.
RNA-Seq-Based Transcriptome Analysis of Nitric Oxide Scavenging Response in Neurospora crassa
Authors: Yu Nan-Nan , Veerana Mayura , Ketya Wirinthip , Sun Hu-Nan , Park Gyungsoon
Published: October 2023

While the biological role of naturally occurring nitric oxide (NO) in filamentous fungi has been uncovered, the underlying molecular regulatory networks remain unclear. In this study, we conducted an analysis of transcriptome profiles to investigate the initial stages of understanding these NO regulatory networks in Neurospora crassa, a well-established model filamentous fungus. Utilizing RNA sequencing, differential gene expression screening, and various functional analyses, our findings revealed that the removal of intracellular NO resulted in the differential transcription of 424 genes. Notably, the majority of these differentially expressed genes were functionally linked to processes associated with carbohydrate and amino acid metabolism. Furthermore, our analysis highlighted the prevalence of four specific protein domains (zinc finger C2H2, PLCYc, PLCXc, and SH3) in the encoded proteins of these differentially expressed genes. Through protein–protein interaction network analysis, we identified eight hub genes with substantial interaction connectivity, with mss-4 and gel-3 emerging as possibly major responsive genes during NO scavenging, particularly influencing vegetative growth. Additionally, our study unveiled that NO scavenging led to the inhibition of gene transcription related to a protein complex associated with ribosome biogenesis. Overall, our investigation suggests that endogenously produced NO in N. crassa likely governs the transcription of genes responsible for protein complexes involved in carbohydrate and amino acid metabolism, as well as ribosomal biogenesis, ultimately impacting the growth and development of hyphae.
The Behavior of Terbuthylazine, Tebuconazole, and Alachlor during Denitrification Process
Authors: Pániková Kristína , Bílková Zuzana , Malá Jitka
Published: October 2023

Pesticide compounds can influence denitrification processes in groundwater in many ways. This study observed behavior of three selected pesticides under denitrifying conditions. Alachlor, terbuthylazine, and tebuconazole, in a concentration of 0.1 mL L−1, were examined using two laboratory denitrifications assays: a “short” 7-day and a “long” 28-day test. During these tests, removal of pesticides via adsorption and biotic decomposition, as well as the efficiency of nitrate removal in the presence of the pesticides, were measured. No considerable inhibition of the denitrification process was observed for any of the pesticides. On the contrary, significant stimulation was observed after 21 days for alachlor (49%) and after seven days for terbuthylazine (40%) and tebuconazole (36%). Adsorption was in progress only during the first seven days in the case of all tested pesticides and increased only negligibly afterwards. Immediate adsorption of terbuthylazine was probably influenced by the mercuric chloride inhibitor. A biotic loss of 4% was measured only in the case of alachlor.
The Silent Threat: Exploring the Ecological and Ecotoxicological Impacts of Chlorinated Aniline Derivatives and the Metabolites on the Aquatic Ecosystem
Authors: Rebelo Daniela , Antunes Sara C. , Rodrigues Sara
Published: October 2023

The growing concern over the environmental impacts of industrial chemicals on aquatic ecosystems has prompted increased attention and regulation. Aromatic amines have drawn scrutiny due to their potential to disturb aquatic ecosystems. 4-chloroaniline and 3,4-dichloroaniline are chlorinated derivatives of aniline used as intermediates in the synthesis of pharmaceuticals, dyes, pesticides, cosmetics, and laboratory chemicals. While industrial applications are crucial, these compounds represent significant risks to aquatic environments. This article aims to shed light on aromatic amines’ ecological and ecotoxicological impacts on aquatic ecosystems, given as examples 4-chloroaniline and 3,4-dichloroaniline, highlighting the need for stringent regulation and management to safeguard water resources. Moreover, these compounds are not included in the current Watch List of the Water Framework Directive, though there is already some information about aquatic ecotoxicity, which raises some concerns. This paper primarily focuses on the inherent environmental problem related to the proliferation and persistence of aromatic amines, particularly 4-chloroaniline and 3,4-dichloroaniline, in aquatic ecosystems. Although significant research underscores the hazardous effects of these compounds, the urgency of addressing this issue appears to be underestimated. As such, we underscore the necessity of advancing detection and mitigation efforts and implementing improved regulatory measures to safeguard the water bodies against these potential threats.
Persistent Social Vulnerability in Washington D.C. Communities and Green Infrastructure Clustering
Authors: Park Minkyu
Published: October 2023

Cities worldwide are presently contending with the intricate task of formulating urban infrastructure that seamlessly blends sustainability and resilience to effectively tackle urgent challenges. An increasingly prominent strategy gaining swift traction is the deployment of green infrastructure (GI), heralding a multitude of advantages for the urban milieu. As a growing body of research highlights the emergence of a new equity issue in our infrastructures from the perspective of environmental justice, it becomes evident that there is a significant gap in comprehensive studies investigating the combined temporal and spatial evolution of green infrastructure (GI) distribution. This research aims to address this gap by adopting a novel approach that explicitly considers the temporal dimension of GI distribution. Unlike previous studies that often rely on cross-sectional snapshots, this study employs a panel data analysis, which allows for a comprehensive examination of how GI distribution evolves over time. The primary research question addressed in this study is whether GI distribution in Washington D.C. exhibits a propensity to concentrate within certain communities. This inquiry delves into the pressing concern of the potential exacerbation of existing disparities through GI implementation. The study’s findings may drive evidence-based policy recommendations that foster equitable distribution strategies, guaranteeing that socially vulnerable communities reap the rewards of GI’s positive impacts.
Postbiotics Production of Candidate-Probiotic Lactiplantibacillus plantarum AC131 with Renewable Bio Resources
Authors: Danova Svetla , Yankov Dragomir , Dobreva Lili , Dobreva Ana , Armenova Nadya , Apostolov Apostol , Mileva Milka
Published: October 2023

Lactiplantibacillus plantarum is a versatile specie, well known as a producer of lactic acid (LA) and other metabolites with biotechnological significance. The present work characterizes growth and lactic acid production of the candidate-probiotic strain L. plantarum AC131, from Bulgarian white brined cheeses. Different nutritional media with ingredients from renewable resources—reduced sugars from dried distillers’ grains with soluble (DDGS) and waste waters from the water-vapor distillation of Bulgarian Rosa alba L. and Rosa damascena Mill. essential oil—were assessed. The results obtained showed significant LA production (up to 95% conversion) in modified MRS broth with reducing sugars from DDGS hydrolysates. The addition of R. alba L. and R. damascena Mill. distillation effluents stimulated the growth and biological activity of postbiotics produced by L. plantarum AC131. In both experimental approaches, a statistically significant inhibition (from 20 to 60%) of E. coli HB 101 growth was found during 24 h exposure and a variable effect on the biofilm formed. In conclusion, reducing sugars from DDGS hydrolysates can be successfully used as a carbon source for lactic acid production. In the case of fermentation without pH control, the process is product inhibited, while with pH control, nearly full conversion was achieved. Postbiotics produced during the process of fermentation showed a variety of biological activity and inhibitory effects on the growth of Escherichia coli HB 101.
Iron Status and Physical Performance in Athletes
Authors: Solberg Andrea , Reikvam Håkon
Published: October 2023

Iron is an important mineral in the body, essential for muscle function and oxygen transport. Adequate levels of iron in the blood are necessary for athletes, as iron-deficiency anemia can reduce physical performance. Several studies have investigated iron status and supplementation in iron-deficient athletes, and determined how physical strain can change iron balance and markers related to iron status. The question of how to influence and optimize iron status, as well as other markers that can affect iron metabolism, has been less thoroughly investigated. Therefore, the aim of this review is to take a closer look at the importance of iron values, iron markers, and factors that can change iron metabolism for physical performance and the extent to which physical performance can be influenced in a positive or negative way. A systematic search of the PubMed database was performed, with the use of « iron» or «iron deficiency» or «hemoglobin» AND «athletes» AND «athletic performance» as a strategy of the search. After the search, 11 articles were included in the review after the application of inclusion and exclusion criteria. Major findings include that iron supplementation had the best effect in athletes with the lowest iron status, and effects on physical performance were mostly achieved in those who were originally in a deficit. Iron supplementation could be beneficial for optimal erythropoietic response during altitude training, even in athletes with normal iron stores at baseline, but should be performed with caution. Alteration of the hepcidin response can affect the use of existing iron stores for erythropoiesis. Energy intake, and the amount of carbohydrates available, may have an impact on the post-exercise hepcidin response. Optimal vitamin D and B12 levels can possibly contribute to improved iron status and, hence, the avoidance of anemia.
Effects of Drilling Parameters and Mud Types on Wear Factors and Mechanisms of SM2535 Casings
Authors: Osman Omer , Merah Necar , Abdul Samad Mohammed , Al-Shaarawi Amjad , Alshalan Meshari
Published: October 2023

This work aims to explore the impact of side loads, drill-pipe tool-joint (DP-TJ) speed (rpm), and mud type on the austenitic stainless steel SM2535-110 casing wear characteristics. Actual field drill pipe tool joints, casings, and drilling muds are used in this study. The results of the study show that under both types of lubrication, the wear volume increased with radial load and DP-TJ speed. SM2535-110 casing specimens tested under oil-based mud (OBM) lubrication had higher casing wear volumes than those obtained under water-based mud (WBM) lubrication. This unexpected behavior is mainly due to the increase in the surface hardness of the casing specimens tested under WBM. The results also show that the specific wear rate or wear factor (K) (which is defined as the volume loss per unit load per unit distance sliding) values of specimens tested under WBM are in general two to four times higher than those obtained under OBM. While K values under WBM increase with both the side load and rpm, those under OBM show a sharp decrease with rpm. This behavior under OBM is due to this lubricant’s higher viscosity and the change of lubrication regime from thin film to thick film lubrication at higher rpm. Scanning electron microscopy (SEM) and the digital microscopic imaging (DMI) of SM235-110 casing specimens show that an aggressive combination of adhesive, abrasive, and plastic deformation was observed under WBM, while the dominant wear mechanism under OBM is abrasive wear.
Multi-Objective Optimization of Process Parameters in Longitudinal-Torsional Ultrasonic Vibration Face Grinding CFRP
Authors: Liu Shuliang , Zheng Kai , Li Hongcheng , Cao Zhengfeng , Zhao Shuang
Published: October 2023

Due to its superior characteristics, carbon fiber reinforced plastics (CFRP) have been widely used in aerospace and other fields. However, their effective and economical processing remains a challenge. The purpose of this paper was to experimentally investigate the influence of several machining parameters, namely spindle speed, cutting depth, feed rate, and grit size on different machining performances, i.e., grinding force, and surface roughness through longitudinal-torsional (L&T) ultrasonic vibration grinding CFRP. The response surface methodology with a Box—Behnken design was used to create the experiments. The fitting mathematical models of grinding force and surface roughness were established separately to explore the interaction between the machining parameters and the impact on machining results. With the purpose of improving the surface quality and reducing the grinding force, the NSGA-II was used for multi-objective optimization to obtain the Pareto optimal solution. Compared with the initial experimental parameters, the optimized results can significantly improve the surface roughness and reduce the cutting force.
Muscle Fatigue Regulation through Muscle Activation Control in a Knee Hybrid Exoskeleton: Simulation Study
Authors: Ghajari Shazan , Moghaddam Reihaneh , Kobravi Hamidreza , Pariz Naser
Published: October 2023

The knee hybrid exoskeleton is a system that aids in the rehabilitation of patients with mobility disorders. It comprises a powered exoskeleton and functional electrical stimulation, which moves the knee joint by stimulating the muscles. However, electrical stimulation of muscles can lead to muscle fatigue. For the first time, this article investigates the regulation of muscle fatigue by controlling muscle activation. To control muscle activation, an innovative adaptive controller for FES is designed. The adaptation law is designed utilizing a time-varying estimation of the muscle activation time parameter. The proportional-integral controller is designed to regulate the knee joint angle utilizing an electrical motor. The proportional-integral controller gains are calculated using an optimization method. A cooperative control structure is presented to use the electrical motor and functional electrical stimulation simultaneously. The muscle activation error is uniformly ultimately bounded, and its boundedness is proven through Lyapunov analysis; the error bound is also determined. The simulation results showed knee joint angle regulation and muscle fatigue regulation. The proposed control method results were compared with those based on model predictive control and switching control, which showed significant improvement in the joint angle error and muscle fatigue. The proposed method is appropriate for practical implementation based on the obtained results.
New Monotonicity and Infinite Divisibility Properties for the Mittag-Leffler Function and for Stable Distributions
Authors: Altaymani Nuha , Jedidi Wissem
Published: October 2023

Hyperbolic complete monotonicity property (HCM) is a way to check if a distribution is a generalized gamma (GGC), hence is infinitely divisible. In this work, we illustrate to which extent the Mittag-Leffler functions Eα,α∈(0,2], enjoy the HCM property, and then intervene deeply in the probabilistic context. We prove that for suitable α and complex numbers z, the real and imaginary part of the functions x↦Eαzx, are tightly linked to the stable distributions and to the generalized Cauchy kernel.
Codimension-Two Bifurcations of a Simplified Discrete-Time SIR Model with Nonlinear Incidence and Recovery Rates
Authors: Hu Dongpo , Liu Xuexue , Li Kun , Liu Ming , Yu Xiao
Published: October 2023

In this paper, a simplified discrete-time SIR model with nonlinear incidence and recovery rates is discussed. Here, using the integral step size and the intervention level as control parameters, we mainly discuss three types of codimension-two bifurcations (fold-flip bifurcation, 1:3 resonance, and 1:4 resonance) of the simplified discrete-time SIR model in detail by bifurcation theory and numerical continuation techniques. Parameter conditions for the occurrence of codimension-two bifurcations are obtained by constructing the corresponding approximate normal form with translation and transformation of several parameters and variables. To further confirm the accuracy of our theoretical analysis, numerical simulations such as phase portraits, bifurcation diagrams, and maximum Lyapunov exponents diagrams are provided. In particular, the coexistence of bistability states is observed by giving local attraction basins diagrams of different fixed points under different integral step sizes. It is possible to more clearly illustrate the model’s complex dynamic behavior by combining theoretical analysis and numerical simulation.
Optimal Investment–Consumption–Insurance Problem of a Family with Stochastic Income under the Exponential O-U Model
Authors: Wang Yang , Lin Jianwei , Chen Dandan , Zhang Jizhou
Published: October 2023

A household consumption and optimal portfolio problem pertinent to life insurance (LI) in a continuous time setting is examined. The family receives a random income before the parents’ retirement date. The price of the risky asset is driven by the exponential Ornstein–Uhlenbeck (O-U) process, which can better reflect the state of the financial market. If the parents pass away prior to their retirement time, the children do not have any work income and LI can be purchased to hedge the loss of wealth due to the parents’ accidental death. Meanwhile, utility functions (UFs) of the parents and children are individually taken into account in relation to the uncertain lifetime. The purpose of the family is to appropriately maximize the weighted average of the corresponding utilities of the parents and children. The optimal strategies of the problem are achieved using a dynamic programming approach to solve the associated Hamilton–Jacobi–Bellman (HJB) equation by employing the convex dual theory and Legendre transform (LT). Finally, we aim to examine how variations in the weight of the parents’ UF and the coefficient of risk aversion affect the optimal policies.
A Comparative Study of Nafion 212 and Sulfonated Poly(Ether Ether Ketone) Membranes with Different Degrees of Sulfonation on the Performance of Iron-Chromium Redox Flow Battery
Authors: Bai Enrui , Zhu Haotian , Sun Chuanyu , Liu Guanchen , Xie Xiaoyin , Xu Chongyang , Wu Sheng
Published: October 2023

For an iron-chromium redox flow battery (ICRFB), sulfonated poly(ether ether ketone) (SPEEK) membranes with five various degrees of sulfonation (DSs) are studied. To select the SPEEK membrane with the ideal DS for ICRFB applications, the physicochemical characteristics and single-cell performance are taken into consideration. Following all the investigations, it has been determined that the SPEEK membrane, which has a DS of 57% and a thin thickness of 25 μm, is the best option for replacing commercial Nafion 212 in ICRFB. Firstly, it exhibits a better cell performance according to energy efficiency (EE) and coulombic efficiency (CE) at the current density range between 40 mA cm−2 and 80 mA cm−2. Additionally, it has a more stable EE (79.25–81.64%) and lower discharge capacity decay rate (50%) than the Nafion 212 (EE: 76.74–81.45%, discharge capacity decay: 76%) after 50 charge–discharge cycles, which proves its better oxidation stability as well. In addition, the longer self-discharge time during the open-circuit voltage test further demonstrates that this SPEEK membrane could be employed for large-scale ICRFB applications.
Effectiveness of Digital and Analog Stress Management Interventions within Occupational Health Management in the Public Sector
Authors: Fasthoff Runa Maj , Nolte Lea , Kortsch Timo
Published: October 2023

Stress increases among the working population in Germany. Workplace stress management interventions are therefore becoming increasingly important, especially in the public sector, which has a higher structural risk for work-related stress than other organizations. Currently, face-to-face formats dominate, but promising digital offerings are being developed. The aim of this study was to investigate the effectiveness of a stress management intervention as a face-to-face and self-guided digital format, referring to the Job Demands-Resources Model. The preregistered study applied a randomized control group design in which N = 65 public service employees were assigned to face-to-face training, an online course, or waitlist control group. Participants completed online questionnaires before the intervention, shortly after the intervention, and six weeks later. Although trends for reductions in emotional exhaustion and perceived stress were evident among the intervention groups, mixed analyses of variance showed no interaction effects between the time and group on the outcomes. The main effects showed a significant decrease in stress levels regardless of the group and significant differences between intervention groups, with the online course reporting the lowest stress level. The results indicate that digital and analog stress management interventions can have desired effects within occupational health management. However, many unpredictable events (e.g., illness, vacation during the intervention) seem to influence the effectiveness in the workplace setting, and so further research is needed.
Biomarker Discovery for Hepatocellular Carcinoma in Patients with Liver Cirrhosis Using Untargeted Metabolomics and Lipidomics Studies
Authors: Rashid Md Mamunur , Varghese Rency S. , Ding Yuansong , Ressom Habtom W.
Published: October 2023

Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is the third leading cause of mortality globally. Patients with HCC have a poor prognosis due to the fact that the emergence of symptoms typically occurs at a late stage of the disease. In addition, conventional biomarkers perform suboptimally when identifying HCC in its early stages, heightening the need for the identification of new and more effective biomarkers. Using metabolomics and lipidomics approaches, this study aims to identify serum biomarkers for identification of HCC in patients with liver cirrhosis (LC). Serum samples from 20 HCC cases and 20 patients with LC were analyzed using ultra-high-performance liquid chromatography-Q Exactive mass spectrometry (UHPLC-Q-Exactive-MS). Metabolites and lipids that are significantly altered between HCC cases and patients with LC were identified. These include organic acids, amino acids, TCA cycle intermediates, fatty acids, bile acids, glycerophospholipids, sphingolipids, and glycerolipids. The most significant variability was observed in the concentrations of bile acids, fatty acids, and glycerophospholipids. In the context of HCC cases, there was a notable increase in the levels of phosphatidylethanolamine and triglycerides, but the levels of fatty acids and phosphatidylcholine exhibited a substantial decrease. In addition, it was observed that all of the identified metabolites exhibited a superior area under the receiver operating characteristic (ROC) curve in comparison to alpha-fetoprotein (AFP). The pathway analysis of these metabolites revealed fatty acid, lipid, and energy metabolism as the most impacted pathways. Putative biomarkers identified in this study will be validated in future studies via targeted quantification.
Benchmarking Metagenomic Classifiers on Simulated Ancient and Modern Metagenomic Data
Authors: Pusadkar Vaidehi , Azad Rajeev K.
Published: October 2023

Taxonomic profiling of ancient metagenomic samples is challenging due to the accumulation of specific damage patterns on DNA over time. Although a number of methods for metagenome profiling have been developed, most of them have been assessed on modern metagenomes or simulated metagenomes mimicking modern metagenomes. Further, a comparative assessment of metagenome profilers on simulated metagenomes representing a spectrum of degradation depth, from the extremity of ancient (most degraded) to current or modern (not degraded) metagenomes, has not yet been performed. To understand the strengths and weaknesses of different metagenome profilers, we performed their comprehensive evaluation on simulated metagenomes representing human dental calculus microbiome, with the level of DNA damage successively raised to mimic modern to ancient metagenomes. All classes of profilers, namely, DNA-to-DNA, DNA-to-protein, and DNA-to-marker comparison-based profilers were evaluated on metagenomes with varying levels of damage simulating deamination, fragmentation, and contamination. Our results revealed that, compared to deamination and fragmentation, human and environmental contamination of ancient DNA (with modern DNA) has the most pronounced effect on the performance of each profiler. Further, the DNA-to-DNA (e.g., Kraken2, Bracken) and DNA-to-marker (e.g., MetaPhlAn4) based profiling approaches showed complementary strengths, which can be leveraged to elevate the state-of-the-art of ancient metagenome profiling.
Zinc-Doped Iron Oxide Nanoparticles as a Proton-Activatable Agent for Dose Range Verification in Proton Therapy
Authors: Ibáñez-Moragues Marta , Fernández-Barahona Irene , Santacruz Rocío , Oteo Marta , Luján-Rodríguez Víctor M. , Muñoz-Hernando María , Magro Natalia , Lagares Juan I. , Romero Eduardo , España Samuel , Espinosa-Rodríguez Andrea , García-Díez Miguel , Martínez-Nouvilas Víctor , Sánchez-Tembleque Víctor , Udías José Manuel , Valladolid-Onecha Víctor , Martín-Rey Miguel Á. , Almeida-Cordon Edilia I. , Viñals i Onsès Sílvia , Pérez José Manuel , Fraile Luis Mario , Herranz Fernando , Morcillo Miguel Ángel
Published: October 2023

Proton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 μg Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1–10 μg Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field.
Phytochemical Composition and Antioxidant and Anti-Inflammatory Activities of Humboldtia sanjappae Sasidh. & Sujanapal, an Endemic Medicinal Plant to the Western Ghats
Authors: Sidhic Jameema , George Satheesh , Alfarhan Ahmed , Rajagopal Rajakrishnan , Olatunji Opeyemi Joshua , Narayanankutty Arunaksharan
Published: October 2023

Ethnomedicinal plants are important sources of drug candidates, and many of these plants, especially in the Western Ghats, are underexplored. Humboldtia, a genus within the Fabaceae family, thrives in the biodiversity of the Western Ghats, Kerala, India, and holds significant ethnobotanical importance. However, many Humboldtia species remain understudied in terms of their biological efficacy, while some lack scientific validation for their traditional uses. However, Humboldtia sanjappae, an underexplored plant, was investigated for the phytochemical composition of the plant, and its antioxidant, enzyme-inhibitory, anti-inflammatory, and antibacterial activities were assessed. The LC-MS analysis indicated the presence of several bioactive substances, such as Naringenin, Luteolin, and Pomiferin. The results revealed that the ethanol extract of H. sanjappae exhibited significant in vitro DPPH scavenging activity (6.53 ± 1.49 µg/mL). Additionally, it demonstrated noteworthy FRAP (Ferric Reducing Antioxidant Power) activity (8.46 ± 1.38 µg/mL). Moreover, the ethanol extract of H. sanjappae exhibited notable efficacy in inhibiting the activities of α-amylase (47.60 ± 0.19µg/mL) and β-glucosidase (32.09 ± 0.54 µg/mL). The pre-treatment with the extract decreased the LPS-stimulated release of cytokines in the Raw 264.7 macrophages, demonstrating the anti-inflammatory potential. Further, the antibacterial properties were also evident in both Gram-positive and Gram-negative bacteria. The observed high zone of inhibition in the disc diffusion assay and MIC values were also promising. H. sanjappae displays significant anti-inflammatory, antioxidant, antidiabetic, and antibacterial properties, likely attributable to its rich composition of various biological compounds such as Naringenin, Luteolin, Epicatechin, Maritemin, and Pomiferin. Serving as a promising reservoir of these beneficial molecules, the potential of H. sanjappae as a valuable source for bioactive ingredients within the realms of nutraceutical and pharmaceutical industries is underscored, showcasing its potential for diverse applications.
Exploring the Solubility Limits of Edaravone in Neat Solvents and Binary Mixtures: Experimental and Machine Learning Study
Authors: Przybyłek Maciej , Jeliński Tomasz , Mianowana Magdalena , Misiak Kinga , Cysewski Piotr
Published: October 2023

This study explores the edaravone solubility space encompassing both neat and binary dissolution media. Efforts were made to reveal the inherent concentration limits of common pure and mixed solvents. For this purpose, the published solubility data of the title drug were scrupulously inspected and cured, which made the dataset consistent and coherent. However, the lack of some important types of solvents in the collection called for an extension of the available pool of edaravone solubility data. Hence, new measurements were performed to collect edaravone solubility values in polar non-protic and diprotic media. Such an extended set of data was used in the machine learning process for tuning the parameters of regressor models and formulating the ensemble for predicting new data. In both phases, namely the model training and ensemble formulation, close attention was paid not only to minimizing the deviation of computed values from the experimental ones but also to ensuring high predictive power and accurate solubility computations for new systems. Furthermore, the environmental friendliness characteristics determined based on the common green solvent selection criteria, were included in the analysis. Our applied protocol led to the conclusion that the solubility space defined by ordinary solvents is limited, and it is unlikely to find solvents that are better suited for edaravone dissolution than those described in this manuscript. The theoretical framework presented in this study provides a precise guideline for conducting experiments, as well as saving time and resources in the pursuit of new findings.
Insight into the Metal–Support Interaction of Pt and β-MnO2 in CO Oxidation
Authors: Zhang Tiantian , Xu Jiacheng , Sun Yan , Fang Shiyu , Wu Zuliang , Gao Erhao , Zhu Jiali , Wang Wei , Yao Shuiliang , Li Jing
Published: October 2023

Pt-based catalysts exhibit unique catalytic properties in many chemical reactions. In particular, metal–support interactions (MSI) greatly improve catalytic activity. However, the current MSI mechanism between platinum (Pt) and the support is not clear enough. In this paper, the interaction of 1 wt% Pt nanoparticles (NPs) on β-MnO2 in carbon monoxide (CO) oxidation was studied. The Pt on β-MnO2 inhibited CO oxidation below 210 °C but promoted it above 210 °C. A Pt/β-MnO2 catalyst contains more Pt4+ and less Pt2+. The results of operando DRIFTS-MS show that surface-terminal-type oxygen (M=O) plays an important role in CO oxidation. When the temperature was below 210 °C, Mn=O consumption on Pt/β-MnO2 was less than β-MnO2 due to Pt4+ inhibition on CO oxidation. When the temperature was above 210 °C, Pt4+ was reduced to Pt2+, and Mn=O consumption due to CO oxidation was greater than β-MnO2. The interaction of Pt and β-MnO2 is proposed.
Simultaneous Determination of Pesticide Residues and Mycotoxins in Storage Pu-erh Tea Using Ultra-High-Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry
Authors: Chau Siu Leung , Zhao Aihua , Jia Wei , Wang Lu
Published: October 2023

Mycotoxins and pesticides are the most concerning chemical contaminants that can affect the quality of Pu-erh tea during its production and storage. This study presents a method that can simultaneously determine 31 pesticide residues and six mycotoxins in Pu-erh tea within 11 min using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) after QuEChERS extraction. The lower limit of quantification (LOQ) for all analytes ranged between 0.06 and 50 ppb. Recoveries for each pesticide and mycotoxin ranged between 62.0 and 130.3%, with intra- and inter-day precisions lower than 15%. Good linear relationships were obtained, with correlation coefficients of r2 > 0.991 for all analytes. The established method was applied to 31 Pu-erh tea samples, including raw and ripened Pu-erh tea with different storage times. As a result, pesticide residues were not detected in any of the collected samples, and the mycotoxins detected in the samples were well below the official maximum residue limits (MRLs). Notably, the levels of aflatoxin B1 (AFB1), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) were lower than 1 ppb in the samples stored for more than 30 years.
Exploring the Steps of Infrared (IR) Spectral Analysis: Pre-Processing, (Classical) Data Modelling, and Deep Learning
Authors: Mokari Azadeh , Guo Shuxia , Bocklitz Thomas
Published: October 2023

Infrared (IR) spectroscopy has greatly improved the ability to study biomedical samples because IR spectroscopy measures how molecules interact with infrared light, providing a measurement of the vibrational states of the molecules. Therefore, the resulting IR spectrum provides a unique vibrational fingerprint of the sample. This characteristic makes IR spectroscopy an invaluable and versatile technology for detecting a wide variety of chemicals and is widely used in biological, chemical, and medical scenarios. These include, but are not limited to, micro-organism identification, clinical diagnosis, and explosive detection. However, IR spectroscopy is susceptible to various interfering factors such as scattering, reflection, and interference, which manifest themselves as baseline, band distortion, and intensity changes in the measured IR spectra. Combined with the absorption information of the molecules of interest, these interferences prevent direct data interpretation based on the Beer–Lambert law. Instead, more advanced data analysis approaches, particularly artificial intelligence (AI)-based algorithms, are required to remove the interfering contributions and, more importantly, to translate the spectral signals into high-level biological/chemical information. This leads to the tasks of spectral pre-processing and data modeling, the main topics of this review. In particular, we will discuss recent developments in both tasks from the perspectives of classical machine learning and deep learning.
Chlorambucil-Bearing Hybrid Molecules in the Development of Potential Anticancer Agents
Authors: Peter Sijongesonke , Aderibigbe Blessing Atim
Published: October 2023

Increasing cases of cancer have been a primary concern in recent decades. Developing new chemotherapeutics is challenging and has been faced with limitations, such as multidrug resistance, poor specificity, selectivity, and toxicity. The aforementioned factors contribute to treatment failure. Hybrid compounds have features that can overcome the limitations mentioned above. Chlorambucil, an anticancer drug that is used to treat prostate and breast cancer, suffers from poor aqueous solubility and specificity, a short half-life, and severe side effects, including anaemia and bone marrow suppression. It compromises the immune system, resulting in treatment failure. Hence, its combination with other pharmacophores has been reported to result in effective anticancer agents with fewer side effects and high therapeutic outcomes. Furthermore, this review gives an update (2010 to date) on the developments of chlorambucil hybrid compounds with anticancer activity, and the structure-activity relationship (SAR), and also highlights future strategies for developing novel anticancer agents.
Simultaneously Determined Antioxidant and Pro-Oxidant Activity of Randomly Selected Plant Secondary Metabolites and Plant Extracts
Authors: Maliar Tibor , Maliarová Mária , Blažková Marcela , Kunštek Marek , Uváčková Ľubica , Viskupičová Jana , Purdešová Andrea , Beňovič Patrik
Published: October 2023

Oxidative stress is a well-known phenomenon arising from physiological and nonphysiological factors, defined by the balance between antioxidants and pro-oxidants. While the presence and uptake of antioxidants are crucial, the pro-oxidant effects have not received sufficient research attention. Several methods for assessing pro-oxidant activity, utilizing various mechanisms, have been published. In this paper, we introduce a methodology for the simultaneous determination of antioxidant and pro-oxidant activity on a single microplate in situ, assuming that the FRAP method can measure both antioxidant and pro-oxidant activity due to the generation of pro-oxidant Fe2+ ions in the Fenton reaction. Systematic research using this rapid screening method may help to distinguish between compounds with dominant antioxidant efficacy and those with dominant pro-oxidant effects. Our preliminary study has revealed a dominant pro-oxidant effect for compounds with a higher number of oxygen heteroatoms, especially sp2 hybridized compounds (such as those containing keto groups), such as flavonoids and plant extracts rich in these structural types. Conversely, catechins, carotenoids, and surprisingly, extracts from birch leaves and chestnut leaves have demonstrated dominant antioxidant activity over pro-oxidant. These initial findings have sparked significant interest in the systematic evaluation of a more extensive collection of compounds and plant extracts using the developed method.
Ultrasound Assisted Coextraction of Cornicabra Olives and Thyme to Obtain Flavored Olive Oils
Authors: Peres Fátima , Marques Madalena Pinho , Mourato Miguel , Martins Luisa L. , Ferreira-Dias Suzana
Published: October 2023

Flavoring olive oils is a new trend in consumer preferences, and different enrichment techniques can be used. Coextraction of olives with a flavoring agent is an option for obtaining a flavored product without the need for further operations. Moreover, ultrasound (US) assisted extraction is an emergent technology able to increase extractability. Combining US and coextraction, it is possible to obtain new products using different types of olives (e.g., cultivar and ripening stage), ingredient(s) with the greatest flavoring and/or bioactive potential, as well as extraction conditions. In the present study, mastic thyme (Thymus mastichina L.) (TM) and lemon thyme (Thymus x citriodorus) (TC) were used for flavoring Cornicabra oils by coextraction. The coextraction trials were performed by (i) thyme addition to the olives during crushing or malaxation and (ii) US application before malaxation. Several parameters were evaluated in the oil: quality criteria parameters, total phenols, fatty acid composition, chlorophyll pigments, phenolic profile and oxidative stability. US application did not change the phenolic profile of Cornicabra olive oils, while the enrichment of olive oils with phenolic compounds or pigments by coextraction was very dependent on the thyme used. TM enrichment showed an improvement of several new phenolic compounds in the oils, while with TC, fewer new phenols were observed. In turn, in the trials with TC, the extraction of chlorophyll pigments was higher, particularly in crushing coprocessing. Moreover, the oils obtained with US and TM added in the mill or in the malaxator showed lower phenol decrease (59%) than oils flavored with TC (76% decrease) or Cornicabra virgin olive oil (80% decrease) over an 8-month storage period. Multivariate data analysis, considering quality parameters, pigments and phenolic contents, showed that flavored oils were mainly grouped by age.
Differences of Atomic-Level Interactions between Midazolam and Two CYP Isoforms 3A4 and 3A5
Authors: Liu Shuhui , Zheng Qingchuan , Bai Fuquan
Published: October 2023

CYP 3A4 and CYP 3A5 are two important members of the human cytochrome P450 family. Although their overall structures are similar, the local structures of the active site are different, which directly leads to obvious individual differences in drug metabolic efficacy and toxicity. In this work, midazolam (MDZ) was selected as the probe substrate, and its interaction with two proteins, CYP 3A4 and CYP 3A5, was studied by molecular dynamics simulation (MD) along with the calculation of the binding free energy. The results show that two protein–substrate complexes have some similarities in enzyme–substrate binding; that is, in both complexes, Ser119 forms a high occupancy hydrogen bond with MDZ, which plays a key role in the stability of the interaction between MDZ and the enzymes. However, the complex formed by CYP 3A4 and MDZ is more stable, which may be attributed to the sandwich structure formed by the fluorophenyl group of the substrate with Leu216 and Leu482. Our study interprets the binding differences between two isoform–substrate complexes and reveals a structure–function relationship from the atomic perspective, which is expected to provide a theoretical basis for accurately measuring the effectiveness and toxicity of drugs for individuals in the era of precision medicine.