bluuebunny/crossref_metadata_2025 huggingface dataset:
Special Issue: Advances in International Management Research
Authors: Ramon Jeronimo Juan Manuel , Flórez López Raquel
Published: January 2024

Departing from barriers faced by firms in their international entrepreneurship strategies, the establishment of collaborative networks has proven to be a facilitating mechanism of these processes, having in recent years overcome the focus on the supply chain (i [...]
New Insights into HIV Life Cycle, Th1/Th2 Shift during HIV Infection and Preferential Virus Infection of Th2 Cells: Implications of Early HIV Treatment Initiation and Care
Authors: Hokello Joseph , Tyagi Kratika , Owor Richard Oriko , Sharma Adhikarimayum Lakhikumar , Bhushan Alok , Daniel Rene , Tyagi Mudit
Published: January 2024

The theory of immune regulation involves a homeostatic balance between T-helper 1 (Th1) and T-helper 2 (Th2) responses. The Th1 and Th2 theories were introduced in 1986 as a result of studies in mice, whereby T-helper cell subsets were found to direct different immune response pathways. Subsequently, this hypothesis was extended to human immunity, with Th1 cells mediating cellular immunity to fight intracellular pathogens, while Th2 cells mediated humoral immunity to fight extracellular pathogens. Several disease conditions were later found to tilt the balance between Th1 and Th2 immune response pathways, including HIV infection, but the exact mechanism for the shift from Th1 to Th2 cells was poorly understood. This review provides new insights into the molecular biology of HIV, wherein the HIV life cycle is discussed in detail. Insights into the possible mechanism for the Th1 to Th2 shift during HIV infection and the preferential infection of Th2 cells during the late symptomatic stage of HIV disease are also discussed.
Laparoscopic Evaluation of the Reproductive Tract in Two Female Polar Bears (Three Procedures) (Ursus maritimus)
Authors: Aldrich Ellison D. , Hendrickson Dean A. , Schmitt Todd L. , Nollens Hendrik H. , Montano Gisele , Steinman Karen J. , O’Brien Justine K. , Robeck Todd R.
Published: January 2024

Polar bears (Ursus maritimus) face a number of challenges that threaten the survival of the species. Captive breeding represents one essential facet of species conservation, but aspects of the polar bear’s reproductive physiology, such as follicle maturation, coitus-induced ovulation, and pseudopregnancy, are poorly characterized and present challenges for enhancing natural reproductive success and the application of advanced reproductive techniques. Due to the absence of a reliable transrectal or transabdominal ultrasound method for ovarian examination in the species, the ovaries of two adult female polar bears were examined laparoscopically to evaluate the feasibility of surgical access to the ovaries, oviduct, and uterus. The minimally invasive procedure was easily and rapidly performed in both bears and all procedures. Direct visual assessment of the ovary was possible after dissection of a fatty bursal sac, which completely enclosed the ovaries. In the second bear, laparoscopic manipulation of the ovary to draw it closer to the body wall enabled transcutaneous ultrasound. Laparoscopy may be a valuable tool to aid in the application of advanced reproductive technologies in polar bears.
Update on Urinary Tract Infection Antibiotic Resistance—A Retrospective Study in Females in Conjunction with Clinical Data
Authors: Mareș Cristian , Petca Răzvan-Cosmin , Popescu Răzvan-Ionuț , Petca Aida , Mulțescu Răzvan , Bulai Cătălin Andrei , Ene Cosmin Victor , Geavlete Petrișor Aurelian , Geavlete Bogdan Florin , Jinga Viorel
Published: January 2024

Urinary tract infections (UTIs) represent a frequent pathology among the female population that has become more and more difficult to treat in the past decade, considering the increase in antibiotic resistance—a serious global public health problem. A cross-sectional retrospective study was conducted for six months to report an update regarding the rates of resistance and susceptibility of uropathogens necessary for optimal treatment. A total of 5487 patients were screened, of which 524 (9.54%) were female patients who met the criteria for inclusion in the study. Escherichia coli was the most common pathogen, representing 290 cases (55.34%), followed by Enterococcus spp. 82 (15.64%). Escherichia coli presented the highest resistance to amoxicillin-clavulanic acid (R = 33.1%), followed by trimethoprim-sulfamethoxazole (R = 32.41%) and levofloxacin (R = 32.06%). The highest sensitivity rates were observed for fosfomycin (S = 96.55%), followed by imipenem (S = 93.1%). Enterococcus spp. showed the highest resistance to levofloxacin (R = 50.0%), followed by penicillin (R = 39.02%). The highest sensitivity was observed for fosfomycin (S = 90.24%), linezolid (S = 89.02%), and nitrofurantoin (S = 86.58%). The second most frequent Gram-negative uropathogen was represented by Klebsiella spp., which had the highest resistance to amoxicillin-clavulanic acid (R = 35.89%), followed by levofloxacin (R = 25.64) and trimethoprim-suflamethoxazole (R = 24.35%). The most frequently associated pathology was an episode of UTI in the previous year, followed by diabetes and chronic kidney disease. Antibiotic resistance is a serious problem for all clinicians who treat UTIs. An up-to-date knowledge of antibiotic resistance rates is a major necessity to stop its evolution. Overall, the highest resistance rates were observed for aminopenicillins, fluoroquinolones, and trimethoprim-sulfamethoxazole. The best susceptibility rates were observed for fosfomycin, nitrofurantoin, and carbapenems. Our report aims to guide clinicians whenever they are forced to prescribe antibiotics empirically.
The Spatial Entropy of Confined Liquids
Authors: Castejón Henry J.
Published: January 2024

Molecular dynamics simulations have been used to investigate the structural changes in confined liquids. The density distribution functions for weakly and strongly interacting liquids were determined and compared to those of a non-interacting system in order to assess the impact of the entropic forces on the equilibrium state of the systems. The effect of the entropic forces was assessed by quantifying the layering on the liquid structure upon confinement. The more pronounced layering obtained for weakly interacting and non-interacting systems indicated that entropic forces are more effective in these systems where an increase in the multiplicity of states does not require a prohibitively high cost in energy.
Effect of Operating Parameters on the Mulching Device Wear Behavior of a Ridging and Mulching Machine
Authors: Zhao Qinxue , Dai Fei , Shi Ruijie , Zhao Wuyun , Xu Pengqing , Deng Huan , Pan Haifu
Published: January 2024

To conduct an in-depth investigation of the impact of various operating parameters on mulching device wear during the operation of full-film dual-row ridging and mulching machine mulching, this paper employed EDEM software to create a 3D discrete element model of how a mulching device interacts with the soil on the seed bed and simulated the dynamic process of the interaction between the mulching device and the soil during the mulching operation. We analyzed the cladding wear process between the cladding device and the cladding sand particles, and two areas of impact wear on the overburden conveyor housing and areas of wear on the chute deflector scratches were detected. A three-factor, three-level Box–Behnken experimental design approach was used, with mathematical modeling of the relationship between the scraper conveyor lifting line speed, seed bed cover, scraper spacing, and wear of the cover device, finding the optimal combination of operating parameters for mulching devices. The results of the simulation test indicated that the mulching device experienced a minimum wear of 0.958 × 10−3 mm at a lifting line speed of 0.7 m·s−1 for the scraper conveyor, a mulching volume of 2.55 kg·s−1 for the seed bed, and a scraper spacing of 98 mm. The results of the field trial validation showed that, in a comparison between simulated wear parts and a mulching operation prototype of the same two wear parts, the established discrete element model appeared reasonable concerning the structural parameters, with a feasible abrasion mechanism process of sand particles on the soil-covering devices, demonstrating the model’s reliability and validity. It can serve as a guide for optimizing the design of mechanized full-film dual-furrow seed bed mulching operation.
A Generalised Method for Friction Optimisation of Surface Textured Seals by Machine Learning
Authors: Brase Markus , Binder Jonathan , Jonkeren Mirco , Wangenheim Matthias
Published: January 2024

Friction behaviour is an important characteristic of dynamic seals. Surface texturing is an effective method to control the friction level without the need to change materials or lubricants. However, it is difficult to put the manual prediction of optimal friction reducing textures as a function of operating conditions into practice. Therefore, in this paper, we use machine learning techniques for the prediction of optimal texture parameters for friction optimisation. The application of pneumatic piston seals serves as an illustrative example to demonstrate the machine learning method and results. The analyses of this work are based on experimentally determined data of surface texture parameters, defined by the dimple diameter, distance, and depth. Furthermore friction data between the seal and the pneumatic cylinder are measured in different friction regimes from boundary over mixed up to hydrodynamic lubrication. A particular innovation of this work is the definition of a generalised method that guides the entire machine learning process from raw data acquisition to model prediction, without committing to only a few learning algorithms. A large number of 26 regression learning algorithms are used to build machine learning models through supervised learning to evaluate the suitability of different models in the specific application context. In order to select the best model, mathematical metrics and tribological relationships, like Stribeck curves, are applied and compared with each other. The resulting model is utilised in the subsequent friction optimisation step, in which optimal surface texture parameter combinations with the lowest friction coefficients are predicted over a defined interval of relative velocities. Finally, the friction behaviour is evaluated in the context of the model and optimal value combinations of the surface texture parameters are identified for different lubrication conditions.
Development and Test of Geogrid with Distributed Deformation Monitoring Function
Authors: Zhang Jiong , Li Yi , Meng Bowen , Ding Jie , She Rui , Ren Shipu , Liu Qifang
Published: January 2024

In recent years, there is a growing demand for materials that can both improve the mechanical properties of structures and carry out health monitoring and risk warning. In this case, in order to realize distributed deformation monitoring, a new method of making geogrid by 3D printing technology is proposed. The grille rib is made by embedding the conductive polymer (ground carbon fiber as conductive filler) into the insulating shell (PLA material) in the specified path, and then the rib is vertically crossed into each other to form a grille sample. In order to study the distributed deformation monitoring function of this grid, a manual push–pull testing machine was used to conduct a load–unload experiment to analyze the change rule of resistance on the grid plane. The following conclusions were obtained: the closer the ribs are to the load bearing point, the greater the change in resistance, and conversely, the farther the ribs are from the load bearing point, the smaller the change in resistance. Depending on the geogrid network characteristics, the electrical resistance distribution on the geogrid plane can be obtained by superimposing the resistance values of the horizontal and longitudinal ribs, then the location and the magnitude of deformation can be estimated. Additionally, this study carried out numerical simulation of the grid model based on ANSYS 15.0 software and compared with the loading experiment results to verify that the force deformation position can be retrieved through the change of resistance.
Preparation and Optimization of the Adsorbent for Phosphorus Removal Using the Response Surface Method
Authors: Zhang Zhanmei , Zou Zuqin , Ren Xiaoyu , Huang Yunxuan , Deng Yang , Zheng Huaili
Published: January 2024

A diatomaceous earth (DE)-based adsorbent DE-Ce was prepared and optimized to remove phosphorus from wastewater. DE was modified through purification–cerium loading, improving its phosphorus adsorption capacity and recycling ability. The preparation conditions were optimized using the Box–Behnken design, and the response surface method was employed to analyze the effects of roasting temperature, cerium concentration, and HCl concentration on the preparation of DE-Ce. Scanning electron microscopy, X-ray fluorescence spectrometry, and X-ray photoelectron spectroscopy were used for characterization, with results indicating that HCl washing can effectively remove impurities. Cerium was mainly loaded onto DE in the form of Ce(OH)3, and pore size and capacity increased following cerium loading, with the formation of a macroporous structure. The obtained DE-Ce adsorbent removed 98.30% phosphorous, with the removal process following the secondary kinetic and Langmuir models. According to material characterization and model analysis results, the phosphorus removal mechanism primarily involves electrostatic adsorption, ligand exchange, and precipitation. Overall, the findings indicate that cerium modification can effectively improve the adsorption capacity of DE.
Knowledge Graph Extraction of Business Interactions from News Text for Business Networking Analysis
Authors: Gohourou Didier , Kuwabara Kazuhiro
Published: January 2024

Network representation of data is key to a variety of fields and their applications including trading and business. A major source of data that can be used to build insightful networks is the abundant amount of unstructured text data available through the web. The efforts to turn unstructured text data into a network have spawned different research endeavors, including the simplification of the process. This study presents the design and implementation of TraCER, a pipeline that turns unstructured text data into a graph, targeting the business networking domain. It describes the application of natural language processing techniques used to process the text, as well as the heuristics and learning algorithms that categorize the nodes and the links. The study also presents some simple yet efficient methods for the entity-linking and relation classification steps of the pipeline.
The k-out-of-n:G System Viewed as a Multi-Server Queue
Authors: Krishnamoorthy Achyutha , Joshua Anu Nuthan , Mathew Ambily P.
Published: January 2024

This paper extends the k-out-of-n:G reliability system to a multi-server queue. We study a multi-server reliability-queuing model with the N-policy of repair. The queuing system considered here has n servers, each of which has identically and exponentially distributed service times with parameter μ. Servers are subject to breakdown at an exponential rate γ. The repair process follows the N-policy of repair. Although these servers work independently of each other, service can be provided only when k functional servers are available in the system. We study the model in the steady state, using the matrix analytic method. We evaluate some associated performance measures and provide graphical/numerical illustrations. We consider an optimization problem, and the results of the study are presented.
A Multi-Objective Mathematical Programming Model for Project-Scheduling Optimization Considering Customer Satisfaction in Construction Projects
Authors: Zohrehvandi Mehrnoosh , Zohrehvandi Shakib , Khalilzadeh Mohammad , Amiri Maghsoud , Jolai Fariborz , Zavadskas Edmundas Kazimieras , Antucheviciene Jurgita
Published: January 2024

The aim of this study was to develop a multi-objective mathematical programming model for the trade-off of time, cost, and quality in the project-scheduling problem (PSP) by taking priorities and resource constraints as well as activity preemption into account. First, a small-sized problem instance that was a sub-project of an oil and gas construction project was used for te validation of the proposed model and algorithm. Subsequently, considering the sensitivity, complexity, and importance of oil and gas projects, the proposed model was implemented in a large-sized oil and gas construction project. Considering the NP-hardness of this problem, the NSGA-II metaheuristic algorithm was used to deal with the time, cost, and quality trade-off problem. Finally, a sensitivity analysis was implemented on the three main parameters of time, cost, and quality to investigate the effects of changes on the results. The findings show that the proposed model is more sensitive to cost changes, so an increase in project costs leads to a drastic change in the values of other objective functions.
SIR Epidemic Model with General Nonlinear Incidence Rate and Lévy Jumps
Authors: Li Shuang
Published: January 2024

This article proposes a stochastic SIR model with general nonlinear incidence and Lévy jumps, which is used to describe diseases spreading in human populations. The model takes into account the randomness and sublinearity of diseases and can more accurately describe the disease transmission process. Firstly, we prove that this stochastic SIR model has a unique global positive solution. Then, sufficient conditions for the extinction of the disease are given. We also discuss the case that the disease persists in the model. In addition, we study the asymptotic behavior of the solution of the stochastic SIR model relative to the equilibrium points of the deterministic SIR model. These results allow us to understand the trends and dynamic changes of diseases in human populations, providing theoretical support for developing more scientific and effective disease control strategies and prevention measures. Finally, we give some examples and numerical simulations to demonstrate the effectiveness and feasibility of the theoretical results.
SHARDA–ARAS: A Methodology for Prioritising Project Managers in Sustainable Development
Authors: Turskis Zenonas , Keršulienė Violeta
Published: January 2024

In sustainable economic development, top-level human capital, especially project management, is paramount. This article integrates the Systematic Hierarchical Attribute Ratio Delphic Rating (SHARDA) method and the Additive Ratio Rating (ARAS) method as a robust framework for identifying and training project managers. The research draws on a diverse panel of experts against the United Nations Sustainable Development Goals (SDGs) backdrop, emphasising stakeholder engagement and transparency in the decision-making processes. This study investigates the complexity of multi-criteria decision-making (MCDM) methods and focuses on SWARA and ARAS methods. These methodologies comprehensively improve the decision-making process, considering a range of subjective criteria. The extended and modified hierarchical SWARA method helps us understand each measure’s importance, while the ARAS method simplifies ranking and selection based on performance ratios. The research methodology seamlessly integrates these methods to form the SHARDA–ARAS methodology that addresses the challenging task of selecting project managers for sustainable development. This methodology guarantees a systematic and inclusive decision-making process, incorporating stakeholder perspectives seamlessly aligned with global sustainability goals. The studio’s innovation is wrapped in the synthesis of SWARA and ARAS into the SHARDA–ARAS methodology, presenting a nuanced and effective tool for project manager selection. Promoting an interconnected and holistic approach that contributes to sustainable development emphasises the methodology’s ability to balance economic, environmental, and social aspects. Thus, the article provides an invaluable method for organisations seeking global sustainable economic development.
Generalized Convergence for Multi-Step Schemes under Weak Conditions
Authors: Behl Ramandeep , Argyros Ioannis K. , Alshehri Hashim , Regmi Samundra
Published: January 2024

We have developed a local convergence analysis for a general scheme of high-order convergence, aiming to solve equations in Banach spaces. A priori estimates are developed based on the error distances. This way, we know in advance the number of iterations required to reach a predetermined error tolerance. Moreover, a radius of convergence is determined, allowing for a selection of initial points assuring the convergence of the scheme. Furthermore, a neighborhood that contains only one solution to the equation is specified. Notably, we present the generalized convergence of these schemes under weak conditions. Our findings are based on generalized continuity requirements and contain a new semi-local convergence analysis (with a majorizing sequence) not seen in earlier studies based on Taylor series and derivatives which are not present in the scheme. We conclude with a good collection of numerical results derived from applied science problems.
Mathematical Modeling of Two Interacting Populations’ Dynamics of Onchocerciasis Disease Spread with Nonlinear Incidence Functions
Authors: Adeyemo Kabiru Michael , Adam Umar Muhammad , Adeniji Adejimi , Oshinubi Kayode
Published: January 2024

The transmission dynamics of onchocerciasis in two interacting populations are examined using a deterministic compartmental model with nonlinear incidence functions. The model undergoes qualitative analysis to examine how it behaves near disease-free equilibrium (DFE) and endemic equilibrium. Using the Lyapunov function, it is demonstrated that the DFE is globally stable when the threshold parameter R0≤1 is taken into account. When R0>1, it suffices to show globally how asymptotically stable the endemic equilibrium is and its existence. We conduct the bifurcation analysis by looking at the possibility of the model’s equilibria coexisting at R0<1 but near R0=1 using the Center Manifold Theory. We use the sensitivity analysis method to understand how some parameters influence the R0, hence the transmission and mitigation of the disease dynamics. Furthermore, we simulate the model developed numerically to understand the population dynamics. The outcome presented in this article offers valuable understanding of the transmission dynamics of onchocerciasis, specifically in the context of two populations that interact with each other, considering the presence of nonlinear incidence.
Acute Central Serous Chorioretinopathy Outbreak during the COVID-19 Pandemic: A Pilot Study
Authors: Yahalomi Tal , Pikkel Yael Sara , Arnon Roee , Kinori Michael , Wood Keren , Pikkel Joseph
Published: January 2024

Background and Objectives: This study aims to investigate the potential association between the COVID-19 pandemic and a new presentation of central serous chorioretinopathy (CSCR). Materials and Methods: A retrospective analysis was conducted, comparing the incidence of new-onset CSCR cases among ophthalmology patients in a regional medical facility in southern Israel between two distinct periods: the COVID-19 pandemic era in Israel, which occurred from 27 February 2020 to 20 December 2020, and the non-pandemic period from calendar years 2018 to 2021, excluding the specific epidemic phase mentioned. Disease severity was evaluated based on recovery time, visual acuity loss, and central macular thickness via OCT. Results: Over the four-year period, 35 new cases of CSCR were recorded. During the COVID-19 pandemic, 17 new cases (0.005% per population) were identified, compared with 18 new cases (0.002% per population) in the preceding three years. The odds ratio for acute CSCR during the pandemic was 2.83 (95% CI, 1.46–5.50) with a p-value of 0.02. CSCR cases during the pandemic seemed to exhibit worse clinical characteristics, though not statistically significant. Additionally, 22.2% of the COVID-19 pandemic group had confirmed COVID-19 cases, which was statistically significantly higher than the general population’s reported cases (6%). Conclusion: The study revealed a statistically significant increase of over 2.5 times in acute CSCR incidence during the COVID-19 pandemic compared with non-pandemic periods. The findings suggest that the pandemic’s stressful changes may have unintended consequences on the occurrence of CSCR, highlighting the importance of mental health support and psychoeducation for affected patients.
Wide Distribution of Teratosphaeria epicoccoides and T. destructans Associated with Diseased Eucalyptus Leaves in Plantations in Southern China
Authors: Chen Bingyin , Wu Wenxia , Chen Shuaifei
Published: January 2024

Species of Mycosphaerellaceae and Teratosphaeriaceae represent over 40% of the fungi identified on eucalypt leaves worldwide. These include some important pathogens that mainly cause leaf blight and spot, and result in increasingly negative impacts on global commercial eucalypt industries. Eucalyptus plantations are commonly cultivated in southern China for solid wood and pulp products. However, the species diversity and geographic distribution of Mycosphaerellaceae and Teratosphaeriaceae, associated with diseased plantation Eucalyptus leaves in China, have not been clarified. In this study, we conducted the first systematic surveys and sample collections of Mycosphaerellaceae- and Teratosphaeriaceae-like fungi from diseased plantation Eucalyptus leaves in southern China. In total, 558 isolates were obtained from 59 sampled sites in five provinces. One isolate was isolated from each tree. According to the disease symptoms, conidia morphological characteristics, and DNA sequence comparisons of ITS, tef1 and tub2 gene regions. The 558 isolates were identified as Teratosphaeria epicoccoides (312 isolates; 55.9%) and T. destructans (246 isolates, 44.1%). Both species were widely distributed in the sampled regions in southern China. The genotypes of T. epicoccoides and T. destructans were determined based on ITS, tef1, and tub2 sequences. The results showed that multiple genotypes of each species of T. epicoccoides and T. destructans exist in China. Additionally, isolates with multiple genotypes were obtained in all five sampled provinces. These results suggest that both T. epicoccoides and T. destructans are not clonal. This study proved that both T. epicoccoides and T. destructans are dominant species and widely distributed on diseased Eucalyptus leaves in southern China. The wide geographic distribution and potential high genetic diversity pose challenges for the disease management of Teratosphaeria leaf blight and leaf spot in China.
Cold Atmospheric Helium Plasma in the Post-COVID-19 Era: A Promising Tool for the Disinfection of Silicone Endotracheal Prostheses
Authors: Silva Diego Morais da , Do Nascimento Fellype , Milhan Noala Vicensoto Moreira , Oliveira Maria Alcionéia Carvalho de , Cardoso Paulo Francisco Guerreiro , Legendre Daniel , Aoki Fabio Gava , Kostov Konstantin Georgiev , Koga-Ito Cristiane Yumi
Published: January 2024

Despite the excellent properties of silicone endotracheal prostheses, their main limitation is the formation of a polymicrobial biofilm on their surfaces. It can cause local inflammation, interfering with the local healing process and leading to further complications in the clinical scenario. The present study evaluated the inhibitory effect of cold atmospheric plasma (CAP) on multispecies biofilms grown on the silicone protheses’ surfaces. In addition to silicone characterization before and after CAP exposure, CAP cytotoxicity on immortalized human bronchial epithelium cell line (BEAS-2B) was evaluated. The aging time test reported that CAP could temporarily change the silicone surface wetting characteristics from hydrophilic (80.5°) to highly hydrophilic (<5°). ATR-FTIR showed no significant alterations in the silicone surficial chemical composition after CAP exposure for 5 min. A significant log reduction in viable cells in monospecies biofilms (log CFU/mL) of C. albicans, S. aureus, and P. aeruginosa (0.636, 0.738, and 1.445, respectively) was detected after CAP exposure. Multispecies biofilms exposed to CAP showed significant viability reduction for C. albicans and S. aureus (1.385 and 0.831, respectively). The protocol was not cytotoxic to BEAS-2B. CAP can be a simple and effective method to delay multispecies biofilm formation inside the endotracheal prosthesis.
Benzofuran Derivatives from Cortex Mori Radicis and Their Cholinesterase-Inhibitory Activity
Authors: Cui Xiang , Huang Zehong , Deng Shanshan , Zhang Yunxia , Li Guoyin , Wang Lining , Deng Yanru , Wu Changjing
Published: January 2024

The phytochemical investigation of Cortex Mori Radicis led to the isolation and identification of a new prenylated benzofuranone (1) and four ring-opening derivatives (2–5) named albaphenol A–E, as well as nigranol A (6), together with ten 2-arylbenzofuran derivatives (7–16). The characterization of the structures of the new compounds and the structural revision of nigranol A (6) were conducted using the comprehensive analysis of spectroscopic data (1D/2D NMR, HRESIMS, CD, and XRD). Compounds 1–16 were tested for their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1 and 4 showed weak BChE-inhibitory activity (IC50 45.5 and 61.0 μM); six 2-arylbenzofuran derivatives showed more-potent BChE-inhibitory activity (IC50 2.5–32.8 μM) than the positive control galantamine (IC50 35.3 μM), while being inactive or weakly inhibitory toward AChE. Cathafuran C (14) exhibited the most potent and selective inhibitory activity against BChE in a competitive manner, with a Ki value of 1.7 μM. The structure–activity relationships of the benzofuran-type stilbenes were discussed. Furthermore, molecular docking and dynamic simulations were performed to clarify the interactions of the inhibitor–enzyme complex.
Analysis of Polyphenol Extract from Hazel Leaf and Ameliorative Efficacy and Mechanism against Hyperuricemia Zebrafish Model via Network Pharmacology and Molecular Docking
Authors: Wang Xinhe , Zhao Jiarui , Lin Zhi , Li Jun , Li Xiaowen , Xu Xinyi , Wang Yuchen , Lv Guangfu , Lin He , Lin Zhe
Published: January 2024

Hazel leaf, a by-product of hazelnuts, is commonly used in traditional folk medicine in Portugal, Sweden, Iran and other regions for properties such as vascular protection, anti-bleeding, anti-edema, anti-infection, and pain relief. Based on our previous studies, the polyphenol extract from hazel leaf was identified and quantified via HPLC fingerprint. The contents of nine compounds including kaempferol, chlorogenic acid, myricetin, caffeic acid, p-coumaric acid, resveratrol, luteolin, gallic acid and ellagic acid in hazel leaf polyphenol extract (ZP) were preliminary calculated, among which kaempferol was the highest with 221.99 mg/g, followed by chlorogenic acid with 8.23 mg/g. The inhibition of ZP on α-glucosidase and xanthine oxidase activities was determined via the chemical method, and the inhibition on xanthine oxidase was better. Then, the effect of ZP on hyperuricemia zebrafish was investigated. It was found that ZP obviously reduced the levels of uric acid, xanthine oxidase, urea nitrogen and creatinine, and up-regulated the expression ofOAT1 and HPRT genes in hyperuricemia zebrafish. Finally, the targeted network pharmacological analysis and molecular docking of nine polyphenol compounds were performed to search for relevant mechanisms for alleviating hyperuricemia. These results will provide a valuable basis for the development and application of hazel leaf polyphenols as functional ingredients.
Combining Experimental and Computational Methods to Produce Conjugates of Anticholinesterase and Antioxidant Pharmacophores with Linker Chemistries Affecting Biological Activities Related to Treatment of Alzheimer’s Disease
Authors: Makhaeva Galina F. , Kovaleva Nadezhda V. , Rudakova Elena V. , Boltneva Natalia P. , Lushchekina Sofya V. , Astakhova Tatiana Y. , Timokhina Elena N. , Serkov Igor V. , Proshin Alexey N. , Soldatova Yuliya V. , Poletaeva Darya A. , Faingold Irina I. , Mumyatova Viktoriya A. , Terentiev Alexey A. , Radchenko Eugene V. , Palyulin Vladimir A. , Bachurin Sergey O. , Richardson Rudy J.
Published: January 2024

Effective therapeutics for Alzheimer’s disease (AD) are in great demand worldwide. In our previous work, we responded to this need by synthesizing novel drug candidates consisting of 4-amino-2,3-polymethylenequinolines conjugated with butylated hydroxytoluene via fixed-length alkylimine or alkylamine linkers (spacers) and studying their bioactivities pertaining to AD treatment. Here, we report significant extensions of these studies, including the use of variable-length spacers and more detailed biological characterizations. Conjugates were potent inhibitors of acetylcholinesterase (AChE, the most active was 17d IC50 15.1 ± 0.2 nM) and butyrylcholinesterase (BChE, the most active was 18d: IC50 5.96 ± 0.58 nM), with weak inhibition of off-target carboxylesterase. Conjugates with alkylamine spacers were more effective cholinesterase inhibitors than alkylimine analogs. Optimal inhibition for AChE was exhibited by cyclohexaquinoline and for BChE by cycloheptaquinoline. Increasing spacer length elevated the potency against both cholinesterases. Structure–activity relationships agreed with docking results. Mixed-type reversible AChE inhibition, dual docking to catalytic and peripheral anionic sites, and propidium iodide displacement suggested the potential of hybrids to block AChE-induced β-amyloid (Aβ) aggregation. Hybrids also exhibited the inhibition of Aβ self-aggregation in the thioflavin test; those with a hexaquinoline ring and C8 spacer were the most active. Conjugates demonstrated high antioxidant activity in ABTS and FRAP assays as well as the inhibition of luminol chemiluminescence and lipid peroxidation in mouse brain homogenates. Quantum-chemical calculations explained antioxidant results. Computed ADMET profiles indicated favorable blood–brain barrier permeability, suggesting the CNS activity potential. Thus, the conjugates could be considered promising multifunctional agents for the potential treatment of AD.
Hydroxylated Tetramethoxyflavone Affects Intestinal Cell Permeability and Inhibits Cytochrome P450 Enzymes
Authors: Jan Kuo-Ching , Gavahian Mohsen
Published: January 2024

Tetramethoxyflavones (TMFs) found in the Citrus genus have garnered considerable interest from food scientists and the health food industry because of their promising biological properties. Nonetheless, there are currently limited data available regarding the effectiveness and bioavailability of “hydroxylated TMFs”, which are flavones known for their potential in disease prevention through dietary means. This study aims to provide insights into the chemical and biological properties of hydroxylated TMF and evaluates its effects on intestinal cell permeability and cytochrome P450 (CYP) inhibition. Liquid chromatography–mass spectrometry (LC-MS) and microsomes analyze the TMFs and hydroxylated TMFs, elucidating cell penetration and metabolic inhibition potential. 3H7-TMF shows the fastest (1-h) transport efficiency in intestinal cells. The Caco-2 cell model exhibits significant transport and absorption efficiency. Dissolved hydroxyl-TMF with hydrophilicity possibly permeates the gut. 3H7-TMF has higher transport efficiency (46%) 3H6-TMF (39%). IC50 values of TMFs (78-TMF, 57-TMF, 3H7-TMF, 3H6-TMF) against CYP enzymes (CYP1A2, CYP2D6, CYP2C9, CYP2C19, CYP3A4) range from 0.15 to 108 μM, indicating potent inhibition. Hydroxyl groups enhance TMF hydrophilicity and membrane permeability. TMFs display varied inhibitory effects due to hydroxyl and methoxy hindrance. This study underscores the strong CYP inhibitory capabilities in these TMFs, implying potential food–drug interactions if used in medicines or supplements. These findings can also help with food nutrition improvement and pharma food developments through innovative approaches for Citrus waste valorization.
Comparative Analysis of Nickel–Phosphine Complexes with Cumulated Double Bond Ligands: Structural Insights and Electronic Interactions via ETS-NOCV and QTAIM Approaches
Authors: Kégl Tímea R. , Kégl Tamás
Published: January 2024

This study presents a comprehensive analysis of nickel–phosphine complexes, specifically Ni(PH3)2(OCCH2), Ni(PH3)2(H2CCO), Ni(PH3)2(H2CCCH2), Ni(PH3)2(NNCH2), and Ni(PH3)2(η1-H2CNN). Utilizing ETS-NOCV analysis, we explored orbital energy decomposition and the Hirshfeld charges of the ligands, providing insights into the electronic structures and donor–acceptor interactions within these complexes. The interactions in the ketene and allene complexes exhibit similar deformation densities and NOCV orbital shapes to those calculated for Ni(PH3)2(NNCH2), indicating consistent interaction characteristics across these complexes. The total interaction energy for all η2 complexes is observed to be over 60 kcal/mol, slightly exceeding that of the analogous carbon dioxide complex reported earlier. Furthermore, the study highlights the stronger back-donation as compared to donor interactions across all η2 complexes. This is further corroborated by Hirshfeld analysis, revealing the charge distribution dynamics within the ligand fragments. The research offers new perspectives on the electron distribution and interaction energies in nickel–phosphine complexes, contributing to a deeper understanding of their catalytic and reactive behaviors.
Stannylenes and Germylenes Stabilized by Tetradentate Bis(amidine) Ligands with a Rigid Naphthalene Backbone
Authors: Acuña Alejandra , Mallet-Ladeira Sonia , Sotiropoulos Jean-Marc , Maerten Eddy , Cabrera Alan R. , Baceiredo Antoine , Kato Tsuyoshi , Rojas René S. , Madec David
Published: January 2024

An unusual series of germylenes and stannylenes stabilized by new tetradentate bis(amidine) ligands RNC(R′)N-linker-NC(R′)NR with a rigid naphthalene backbone has been prepared by protonolysis reaction of Lappert’s metallylenes [M(HMDS)2] (M = Ge or Sn). Germylenes and stannylenes were fully characterized by NMR spectroscopy and X-ray diffraction analysis. DFT calculations have been performed to clarify the structural and electronic properties associated with tetradentate bis(amidine) ligands. Stannylene L1Sn shows reactivity through oxidation, oxidative addition, and transmetalation reactions, affording the corresponding gallium and aluminum derivatives.
Evaluating the Antioxidant and Antidiabetic Properties of Medicago sativa and Solidago virgaurea Polyphenolic-Rich Extracts
Authors: Paun Gabriela , Neagu Elena , Alecu Andreia , Albu Camelia , Seciu-Grama Ana-Maria , Radu Gabriel Lucian
Published: January 2024

The present study evaluated the antioxidant and antidiabetic properties of Medicago sativa and Solidago virgaurea extracts enriched in polyphenolic compounds. The extracts were obtained by accelerated solvent extraction (ASE) and laser irradiation. Then, microfiltration was used for purification, followed by nanofiltration used to concentrate the two extracts. The obtained extracts were analyzed to determine their antioxidant activity using DPPH radical scavenging and reducing power methods. The antidiabetic properties have been investigated in vitro on a murine insulinoma cell line (β-TC-6) by the inhibition of α-amylase and α-glucosidase. M. sativa obtained by laser irradiation and concentrated by nanofiltration showed the highest DPPH• scavenging (EC50 = 105.2 ± 1.1 µg/mL) and reducing power activities (EC50 = 40.98 ± 0.2 µg/mL). M. sativa extracts had higher inhibition on α-amylase (IC50 = 23.9 ± 1.2 µg/mL for concentrated extract obtained after ASE, and 26.8 ± 1.1), while S. virgaurea had the highest α-glucosidase inhibition (9.3 ± 0.9 µg/mL for concentrated extract obtained after ASE, and 8.6 ± 0.7 µg/mL for concentrated extract obtained after laser extraction). The obtained results after evaluating in vitro the antidiabetic activity showed that the treatment with M. sativa and S. virgaurea polyphenolic-rich extracts stimulated the insulin secretion of β-TC-6 cells, both under normal conditions and under hyperglycemic conditions as well. This paper argues that M. sativa and S. virgaurea polyphenolic-rich extracts could be excellent natural sources with promising antidiabetic potential.
Support Effect of Boron Nitride on the First N-H Bond Activation of NH3 on Ru Clusters
Authors: Zhao Li , Zhuang Huimin , Zhang Yixuan , Ma Lishuang , Xi Yanyan , Lin Xufeng
Published: January 2024

Support effect is an important issue in heterogeneous catalysis, while the explicit role of a catalytic support is often unclear for catalytic reactions. A systematic density functional theory computational study is reported in this paper to elucidate the effect of a model boron nitride (BN) support on the first N-H bond activation step of NH3 on Run (n = 1, 2, 3) metal clusters. Geometry optimizations and energy calculations were carried out using density functional theory (DFT) calculation for intermediates and transition states from the starting materials undergoing the N-H activation process. The primary findings are summarized as follows. The involvement of the model BN support does not significantly alter the equilibrium structure of intermediates and transition states in the most favorable pathway (MFP). Moreover, the involvement of BN support decreases the free energy of activation, ΔG≠, thus improving the reaction rate constant. This improvement is more obvious at high temperatures like 673 K than low temperatures like 298 K. The BN support effect leading to the ΔG≠ decrease is most significant for the single Ru atom case among all three cases studied. Finally, the involvement of the model BN may change the spin transition behavior of the reaction system during the N-H bond activation process. All these findings provide a deeper insight into the support effect on the N-H bond activation of NH3 for the supported Ru catalyst in particular and for supported transition metal catalysts in general.
Deciphering the Mechanism by Which Carbon Dioxide Extends the Shelf Life of Raw Milk: A Microbiomics- and Metabolomics-Based Approach
Authors: Zheng Anran , Wei Chaokun , Liu Jun , Bu Ningxia , Liu Dunhua
Published: January 2024

Microbial community succession in raw milk determines its quality and storage period. In this study, carbon dioxide (CO2) at 2000 ppm was used to treat raw milk to investigate the mechanism of extending the shelf life of raw milk by CO2 treatment from the viewpoint of microbial colonies and metabolites. The results showed that the shelf life of CO2-treated raw milk was extended to 16 days at 4 °C, while that of the control raw milk was only 6 days. Microbiomics analysis identified 221 amplicon sequence variants (ASVs) in raw milk, and the alpha diversity of microbial communities increased (p < 0.05) with the extension of storage time. Among them, Pseudomonas, Actinobacteria and Serratia were the major microbial genera responsible for the deterioration of raw milk, with a percentage of 85.7%. A combined metagenomics and metabolomics analysis revealed that microorganisms altered the levels of metabolites, such as pyruvic acid, glutamic acid, 5′-cmp, arginine, 2-propenoic acid and phenylalanine, in the raw milk through metabolic activities, such as ABC transporters, pyrimidine metabolism, arginine and proline metabolism and phenylalanine metabolism, and reduced the shelf life of raw milk. CO2 treatment prolonged the shelf life of raw milk by inhibiting the growth of Gram-negative aerobic bacteria, such as Acinetobacter guillouiae, Pseudomonas fluorescens, Serratia liquefaciens and Pseudomonas simiae.
Sample Preparation Techniques for Growth-Promoting Agents in Various Mammalian Specimen Preceding MS-Analytics
Authors: Klöppner Laura , Harps Lukas Corbinian , Parr Maria Kristina
Published: January 2024

The misuse of growth-promoting drugs such as beta-2 agonists and steroids is a known problem in farming and sports competitions. Prior to the analysis of biological samples via liquid chromatography (LC)–mass spectrometry (MS) or gas chromatography (GC)–MS, sufficient sample preparation is required to reliably identify or determine the residues of drugs. In practice, broad screening methods are often used to save time and analyze as many compounds as possible. This review was conceptualized to analyze the literature from 2018 until October 2023 for sample preparation procedures applied to animal specimens before LC- or GC-MS analysis. The animals were either used in farming or sports. In the present review, solid phase extraction (SPE) was observed as the dominant sample clean-up technique for beta-2 agonists and steroids, followed by protein precipitation. For the extraction of beta-2 agonists, mixed-mode cation exchanger-based SPE phases were preferably applied, while for the steroids, various types of SPE materials were reported. Furthermore, dispersive SPE-based QuEChERs were utilized. Combinatory use of SPE and liquid–liquid extraction (LLE) was observed to cover further drug classes in addition to beta-2 agonists in broader screening methods.
NASCarD (Nanopore Adaptive Sampling with Carrier DNA): A Rapid, PCR-Free Method for SARS-CoV-2 Whole-Genome Sequencing in Clinical Samples
Authors: Terrazos Miani Miguel A. , Borcard Loïc , Gempeler Sonja , Baumann Christian , Bittel Pascal , Leib Stephen L. , Neuenschwander Stefan , Ramette Alban
Published: January 2024

Whole-genome sequencing (WGS) represents the main technology for SARS-CoV-2 lineage characterization in diagnostic laboratories worldwide. The rapid, near-full-length sequencing of the viral genome is commonly enabled by high-throughput sequencing of PCR amplicons derived from cDNA molecules. Here, we present a new approach called NASCarD (Nanopore Adaptive Sampling with Carrier DNA), which allows a low amount of nucleic acids to be sequenced while selectively enriching for sequences of interest, hence limiting the production of non-target sequences. Using COVID-19 positive samples available during the omicron wave, we demonstrate how the method may lead to >99% genome completeness of the SARS-CoV-2 genome sequences within 7 h of sequencing at a competitive cost. The new approach may have applications beyond SARS-CoV-2 sequencing for other DNA or RNA pathogens in clinical samples.
Current Views about the Inflammatory Damage Triggered by Bacterial Superantigens and Experimental Attempts to Neutralize Superantigen-Mediated Toxic Effects with Natural and Biological Products
Authors: Santacroce Luigi , Topi Skender , Charitos Ioannis Alexandros , Lovero Roberto , Luperto Paolo , Palmirotta Raffaele , Jirillo Emilio
Published: January 2024

Superantigens, i.e., staphylococcal enterotoxins and toxic shock syndrome toxin-1, interact with T cells in a different manner in comparison to conventional antigens. In fact, they activate a larger contingent of T lymphocytes, binding outside the peptide-binding groove of the major histocompatibility complex class II. Involvement of many T cells by superantigens leads to a massive release of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-2, IL-6, tumor necrosis factor-alpha and interferon-gamma. Such a storm of mediators has been shown to account for tissue damage, multiorgan failure and shock. Besides conventional drugs and biotherapeutics, experiments with natural and biological products have been undertaken to attenuate the toxic effects exerted by superantigens. In this review, emphasis will be placed on polyphenols, probiotics, beta-glucans and antimicrobial peptides. In fact, these substances share a common functional denominator, since they skew the immune response toward an anti-inflammatory profile, thus mitigating the cytokine wave evoked by superantigens. However, clinical applications of these products are still scarce, and more trials are needed to validate their usefulness in humans.