bluuebunny/crossref_metadata_2025 huggingface dataset:
Slice-Aided Defect Detection in Ultra High-Resolution Wind Turbine Blade Images
Authors: Gohar Imad , Halimi Abderrahim , See John , Yew Weng Kean , Yang Cong
Published: October 2023

The processing of aerial images taken by drones is a challenging task due to their high resolution and the presence of small objects. The scale of the objects varies diversely depending on the position of the drone, which can result in loss of information or increased difficulty in detecting small objects. To address this issue, images are either randomly cropped or divided into small patches before training and inference. This paper proposes a defect detection framework that harnesses the advantages of slice-aided inference for small and medium-size damage on the surface of wind turbine blades. This framework enables the comparison of different slicing strategies, including a conventional patch division strategy and a more recent slice-aided hyper-inference, on several state-of-the-art deep neural network baselines for the detection of surface defects in wind turbine blade images. Our experiments provide extensive empirical results, highlighting the benefits of using the slice-aided strategy and the significant improvements made by these networks on an ultra high-resolution drone image dataset.
Research on Energy-Efficient Disc Pumps: A Review on Physical Models and Energy Efficiency
Authors: Pei Yingju , Liu Qingyou , Ooi Kim Tiow
Published: October 2023

Disc pumps have obvious advantages in dealing with difficult-to-pump media. Energy efficiency and sustainable energy management are important topics with regard to reducing costs and promoting carbon neutrality. Though the concept of the disc pump was proposed in the 1850s, development was slow and limited by its initial model. However, with the development of industries such as petrochemicals and food, the efficient pumping of difficult-to-pump media is much needed, but facing challenges. Therefore, research on energy-efficient disc pumps is particularly important moving forward. In this paper, the available information from the open literature about the research and development of the disc pump will be thoroughly reviewed. It focuses on the historical development, energy efficiency and physical model application of the disc pump. The review ends with a proposal for the direction of future development, and in this aspect, it is proposed that the energy efficiency prediction model based on velocity slip theory, the energy management system based on multi-scenarios and the design method based on energy conversion theory are important. The latest achievements in energy conversion are given. This review also provides a new perspective for the development of energy-efficient disc pumps.
Assessing the Impact of Time-Varying Optimal Vaccination and Non-Pharmaceutical Interventions on the Dynamics and Control of COVID-19: A Computational Epidemic Modeling Approach
Authors: Li Yan , Samreen  , Zada Laique , Ismail Emad A. A. , Awwad Fuad A. , Hassan Ahmed M.
Published: October 2023

Vaccination strategies remain one of the most effective and feasible preventive measures in combating infectious diseases, particularly during the COVID-19 pandemic. With the passage of time, continuous long-term lockdowns became impractical, and the effectiveness of contact-tracing procedures significantly declined as the number of cases increased. This paper presents a mathematical assessment of the dynamics and prevention of COVID-19, taking into account the constant and time-varying optimal COVID-19 vaccine with multiple doses. We attempt to develop a mathematical model by incorporating compartments with individuals receiving primary, secondary, and booster shots of the COVID-19 vaccine in a basic epidemic model. Initially, the model is rigorously studied in terms of qualitative analysis. The stability analysis and mathematical results are presented to demonstrate that the model is asymptotically stable both locally and globally at the COVID-19-free equilibrium state. We also investigate the impact of multiple vaccinations on the COVID-19 model’s results, revealing that the infection risk can be reduced by administrating the booster vaccine dose to those individuals who already received their first vaccine doses. The existence of backward bifurcation phenomena is studied. A sensitivity analysis is carried out to determine the most sensitive parameter on the disease incidence. Furthermore, we developed a control model by introducing time-varying controls to suggest the optimal strategy for disease minimization. These controls are isolation, multiple vaccine efficacy, and reduction in the probability that different vaccine doses do not develop antibodies against the original virus. The existence and numerical solution to the COVID-19 control problem are presented. A detailed simulation is illustrated demonstrating the population-level impact of the constant and time-varying optimal controls on disease eradication. Using the novel concept of human awareness and several vaccination doses, the elimination of COVID-19 infections could be significantly enhanced.
Finite-Time Anti-Saturated Formation Tracking Control of Multiple Unmanned Aerial Vehicles: A Performance Tuning Way
Authors: Chen Taoyi , Lei Yaolin , Peng Huixiang , Chen Yanqiao , Chai Xinghua , Zhang Zeyong
Published: October 2023

A highly effective control method is very important to guarantee the safety of the formation of flying missions for multiple unmanned aerial vehicles (UAVs), especially in the presence of complex flying environments and actuator constraints. In this regard, this paper investigates the formation tracking control problem of multiple UAVs in the presence of actuator saturation. Firstly, a brand-novel finite-time anti-saturated control scheme is proposed for multiple UAVs to track the desired position commands, wherein the tracking performance is tuned by introducing a logarithmic function-based state-mapping policy. Then, an adaptive scheme based on projection rules is devised to compensate for the negative effects brought by the actuator saturation. Based on the proposed formation tracking controller, the finite-time formation tracking performance tuning and control saturation problems can be addressed simultaneously with a comparatively allowable system robustness. Finally, three groups of illustrative examples are organized to verify the effectiveness of the proposed formation tracking control scheme.
Linguistic Multiple-Attribute Decision Making Based on Regret Theory and Minimax-DEA
Authors: Hu Jinyi
Published: October 2023

Given that most current linguistic multiattribute decision-making methods do not consider the optimal efficiency of decision-making units and the psychological behavior of decision makers, a linguistic multiattribute decision-making method based on regret theory, data envelopment analysis, and the minimax reference point method is proposed. First, based on the decision-maker psychology of regret and avoidance, the perceived utility value of each decision-making unit was calculated using the language regret–joy value function. The subjective and optimal efficiency values of each decision-making unit were obtained using the subjective weighting and data envelopment analysis methods, respectively. Next, we considered the best efficiency as the reference point and the subjective efficiency as the decision preference to establish a minimax reference point model. By solving the model, a set of public weights that minimizes the difference between the efficiency values of all decision-making units and their optimal efficiency values can be obtained to sort the decision-making units and select the best. The feasibility of the method was verified using an example of employee evaluation and selection; the effectiveness of the method was demonstrated through comparative analysis with other methods.
Fuzzy Weighted Pareto–Nash Equilibria of Multi-Objective Bi-Matrix Games with Fuzzy Payoffs and Their Applications
Authors: Li Wen , Li Deyi , Feng Yuqiang , Zou Du
Published: October 2023

Based on our previous research, this paper further discusses the multi-objective bi-matrix game with fuzzy payoffs (MBGFP), which is a special case of the fuzzy constrained multi-objective game with fuzzy payoffs. We first prove that any bi-matrix game with interval payoffs (BGIP) has at least one Pareto–Nash equilibrium. Then, with the help of BGIP, we obtain the necessary and sufficient conditions for the existence of fuzzy Pareto–Nash equilibrium of MBGFP. Secondly, based on the bilinear programming method for calculating Nash equilibrium in crisp bi-matrix games, we established a bilinear programming method with parameters for calculating fuzzy Pareto–Nash equilibrium. By considering the importance of each objective to the players, MBGFP is transformed into a bi-matrix game with fuzzy payoffs (BGFP). Furthermore, we obtained the necessary and sufficient conditions for the existence of fuzzy weighted Pareto–Nash equilibrium and its calculation method. Finally, a practical example is used to illustrate the effectiveness of our proposed calculation method.
The Robust Adaptive Control of Leader–Follower Formation in Mobile Robots with Dynamic Obstacle Avoidance
Authors: Parvareh Amirreza , Naderi Soorki Mojtaba , Azizi Aydin
Published: October 2023

In this paper, the problem of formation control with regard to leader–follower mobile robots in the presence of disturbances and model uncertainties, without needing to know the velocity of the leader robot, is presented. For this purpose, at first, a first-order kinematic model of leader–follower and leader–leader formations is obtained, and considering the absolute velocity of the leader robots as an uncertainty, a robust adaptive controller is designed to keep the desired formation. In this case, the upper bound of uncertainty is unknown and is obtained via stable adaptive laws. Afterwards, in order to deal with the accelerated robots and obstacles, second-order leader–follower and leader–leader formation models are obtained from the previous models. A robust adaptive controller is then designed to stabilize the entire system in the presence of disturbances and modeling uncertainties, without needing to know the parameters or matrices of the formation models. In addition, by considering one of the leaders in the leader–leader model as a virtual obstacle, the challenge of avoiding moving obstacles is also addressed in the presence of uncertainties. The simulation results show the effect of the presented controllers in effectively keeping the desired leader–follower formations.
Nitrous Oxide Inhalant Abuse: Preliminary Results from a Cross-Sectional Study on Knowledge, Attitudes, and Practices of Italian Physicians (2023)
Authors: Riccò Matteo , Ferraro Pietro , Corrado Silvia , Bottazzoli Marco , Marchesi Federico
Published: October 2023

Background and Objectives: Nitrous oxide (N2O) has recently emerged as a cheap alternative to other recreational substances. Although legally available, its chronic use is associated with severe neurological and hematological complications due to the irreversible inactivation of vitamin B12. While no reliable data on abuse of N2O in Italy have been provided to date, we assessed the knowledge, attitudes, and practices of Italian medical professionals on the management of N2O abuse cases. Materials and Methods: A cross-sectional study was performed as a web-based survey through a series of Facebook discussion groups (targeted medical professionals: 12,103), and participants were specifically asked about their previous understanding of N2O abuse and whether they had or not any previous experience in this topic. Results: A total 396 medical professionals participated in the survey. Overall, 115 participants had previous knowledge about N2O abuse (29.04%), with higher odds for professionals with a background in emergency medicine (adjusted odds ratio (aOR) 3.075; 95% confidence intervals (95%CI) 1.071 to 8.828) and lower for specialists in psychiatry (aOR 0.328; 95%CI 0.130 to 0.825). Knowledge status on N2O abuse was largely unsatisfying, as knowledge status, reported as a percent value, was estimated to 45.33% ± 24.71. Having previously managed a case of N2O abuse was associated with higher risk perception of the actual severity of this condition (aOR 5.070; 95%CI 1.520 to 16.980). Conclusions: Our study suggests that N2O poisoning cases are occurring in Italian settings but are not reasonably reported to national authorities. As substantial knowledge gaps of Italian medical workforces were identified, we cannot rule out that the actual abuse of N2O in the population may be far larger than currently suspected.
Demographics, Cutaneous Manifestations, and Comorbidities Associated with Progressive Cutaneous Sarcoidosis: A Retrospective Cohort Study
Authors: Lai Jonathan , Almazan Erik , Le Thomas , Taylor Matthew T. , Alhariri Jihad , Kwatra Shawn G.
Published: October 2023

Background: Sarcoidosis is a multisystem granulomatous disease with a wide variety of presentations and clinical courses. Cutaneous manifestations and comorbidities associated with sarcoid prognosis remain understudied. Methods: An EPIC query was run for patients age 18+ at the Johns Hopkins Hospital with a diagnosis of sarcoidosis of the skin according to the ICD-10-CM code D86.3. Data were obtained from a population-based sample of 240 patients from 2015 to 2020. Results: A total of 240 patients were included in the cohort study. The mean (SD) age was 43.76 (11.72) years, and 30% of participants were male; 76.25% of patients identified as black, 19.58% as white, and 4.17% as other. The average age of onset in remissive patients was significantly higher than progressive (47 ± 12 vs. 40 ± 10, p = 0.0005); 49% of black patients experienced progressive sarcoid compared to 32.6% of white patients (p = 0.028). Progressive disease was associated with the presence of lupus pernio (aOR = 3.29, 95% CI, 1.60–6.77) and at least one autoimmune comorbidity (aOR 6.831, 95% CI 1.819–11.843). Conclusions: When controlling for patient demographics, lupus pernio and the presence of at least one autoimmune condition were associated with progressive cutaneous sarcoidosis.
Bone Marrow Aplasia after CAR-T-Cell Therapy for Relapsed/Refractory Burkitt’s Lymphoma
Authors: Kenkel Troy J. , Sridhar Nithya , Hammons Lindsay R. , Hintzke Maria , Shah Nirav N.
Published: October 2023

Chimeric antigen receptor T-cells (CAR-T) are now a standard approach for treating relapsed/refractory B-cell lymphomas. Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) is a newly described entity that can manifest following CAR-T. Bone marrow (BM) aplasia is an uncommon manifestation of IEC-HS reported after CAR-T-cell therapy and is defined as the reduction or absence of hematopoietic progenitor cells resulting in severe pancytopenia. We describe the case of a 44-year-old female with relapsed/refractory Burkitt lymphoma (BL) who received treatment with lisocabtagene maraleucel with her post-CAR-T course complicated by cytokine release syndrome (CRS) and IEC-HS ultimately leading to persistent BM aplasia. She underwent a rescue allogeneic stem cell transplant but ultimately succumbed to progressive disease. IEC-HS is an increasingly recognized complication that occurs after CAR-T treatments that can result in aplasia, a dangerous complication with serious sequelae including infection, transfusion dependence, and high risk for hemorrhage. The underlying mechanism is poorly understood, and further studies are needed to understand how to treat it better.
Simply Versatile: The Use of Peribacillus simplex in Sustainable Agriculture
Authors: Manetsberger Julia , Caballero Gómez Natacha , Soria-Rodríguez Carlos , Benomar Nabil , Abriouel Hikmate
Published: October 2023

Peribacillus simplex is a Gram-positive, spore-forming bacterium derived from a vast range of different origins. Notably, it is part of the plant-growth-promoting rhizobacterial community of many crops. Although members of the Bacillaceae family have been widely used in agriculture, P. simplex has, so far, remained in the shadow of its more famous relatives, e.g., Bacillus subtilis or Bacillus thuringiensis. Recent studies have, however, started to uncover the bacterium’s highly promising and versatile properties, in particular in agricultural and environmental applications. Hence, here, we review the plant-growth-promoting features of P. simplex, as well as its biocontrol activity against a variety of detrimental plant pests in different crops. We further highlight the bacterium’s potential as a bioremediation agent for environmental contaminants, such as metals, pesticide residues, or (crude) oil. Finally, we examine the recent developments in the European regulatory landscape to facilitate the use of microorganisms in plant protection products. Undoubtedly, further studies on P. simplex will reveal additional benefits for agricultural and environmentally friendly applications.
Distribution and Drug Resistance of Bacterial Infection in Hospitalized Patients at the Respiratory Department before and after the COVID-19 Pandemic in Guangzhou, China
Authors: Hao Ling , Yang Xiao , Chen Huiling , Wei Shuquan , Xu Banglao , Zhao Ziwen
Published: October 2023

Since COVID-19 might have a lasting impact on global public health, it is crucial to analyze its effect on drug-resistant bacterial infections in the respiratory system for the prevention and control of hospital infections. This work aimed to investigate the impact of the COVID-19 outbreak on the clinical distribution and antibiotic resistance of bacterial infection among hospitalized patients in the respiratory unit in order to establish strategies to control antibiotic-resistant infections. Electronic clinical data registry records from 2018 to 2022 were retrospectively analyzed. A total of 36,829 clinical specimens, including sputum, bronchoalveolar lavage fluid, blood, and urine, were collected from 16,073 patients admitted to the Guangzhou First People’s Hospital from January 2018 to December 2022. Among them, 2209 samples were culture-positive. The bacterial isolation rates of different types of samples showed a similar trend from 2019 to 2022, with an increase in 2020 and 2022 and a decrease in 2021. Different bacterial species were separated from different types of samples. The most reported pathogens were identified in sputum samples. Gram-positive isolates were prevalent in urine samples, while Gram-negative bacilli were the predominant pathogenic bacteria isolated from respiratory tract and blood samples. Pseudomonas aeruginosa (P. aeruginosa), Acinetobacter baumannii (A. baumannii) complex, and Klebsiella pneumoniae (K. pneumoniae) were the most abundant Gram-negative bacteria in sputum samples, of which A. baumannii complex had the highest resistance to all tested antibiotics except colistin. Notably, there has been a substantial prevalence of carbapenem-resistant P. aeruginosa, A. baumannii, and K. pneumoniae in the past five years. This alarming situation calls for greater attention and precaution with prescribed antibiotics to limit the generation and spread of new multidrug-resistant bacteria and improve therapeutic management.
Mucin Glycans: A Target for Cancer Therapy
Authors: Sun Lingbo , Zhang Yuhan , Li Wenyan , Zhang Jing , Zhang Yuecheng
Published: October 2023

Mucin glycans are an important component of the mucus barrier and a vital defence against physical and chemical damage as well as pathogens. There are 20 mucins in the human body, which can be classified into secreted mucins and transmembrane mucins according to their distributions. The major difference between them is that secreted mucins do not have transmembrane structural domains, and the expression of each mucin is organ and cell-specific. Under physiological conditions, mucin glycans are involved in the composition of the mucus barrier and thus protect the body from infection and injury. However, abnormal expression of mucin glycans can lead to the occurrence of diseases, especially cancer, through various mechanisms. Therefore, targeting mucin glycans for the diagnosis and treatment of cancer has always been a promising research direction. Here, we first summarize the main types of glycosylation (O-GalNAc glycosylation and N-glycosylation) on mucins and the mechanisms by which abnormal mucin glycans occur. Next, how abnormal mucin glycans contribute to cancer development is described. Finally, we summarize MUC1-based antibodies, vaccines, radio-pharmaceuticals, and CAR-T therapies using the best characterized MUC1 as an example. In this section, we specifically elaborate on the recent new cancer therapy CAR-M, which may bring new hope to cancer patients.
Coffee Silverskin Phytocompounds as a Novel Anti-Aging Functional Food: A Pharmacoinformatic Approach Combined with In Vitro Study
Authors: Hayes Clarin , Nurkolis Fahrul , Laksemi Dewa Ayu Agus Sri , Chung Sanghyun , Park Moon Nyeo , Choi Min , Choi Jinwon , Darmaputra I Gusti Nyoman , Gunawan William Ben , Lele Juan Alessandro Jeremis Maruli Nura , Khumaidi Mohammad Adib , Taslim Nurpudji Astuti , Kim Bonglee
Published: October 2023

Coffee became a beverage that was in demand in the world and consequently produced millions of tons of coffee byproducts namely coffee silverskin (CS). Unutilized CS will be waste and cause environmental pollution such as greenhouse gas emissions, landfill waste, and groundwater contamination. This is a research concern at this time, although many studies have been conducted to find newer applications of CS, exploration of its benefits in the health sector is still limited. Therefore, exploring the benefits of CS to prevent or delay aging will be very interesting to develop in functional food industry technology. Therefore, this study aims to report profiling metabolites or phytochemicals, biological activities in terms of antioxidant activity, and potential anti-aging of CS via molecular docking simulation and in vitro modulation of the mTOR/AMPK/SIRT1 pathway. Something new has been obtained from this work, the profile of phytocompounds, and biological activities both in molecular docking simulation and in vitro studies. Some of the compounds observed in Robusta CS extract (rCSE) such as Epicatechin, Kaempferol, and Quercitrin, and Arabica CS extract (aCSE) such as (+)-Catechin dan Naringin have promising potential as inhibitors of iNOS, mTOR, and HIF-1α via molecular docking simulation. Interestingly, the in vitro biological activity assay of antioxidant and anti-aging activity, rCSE showed the same promising potential as the results of a molecular docking simulation. More interestingly, AMPK/SIRT1/mTOR expressions are well modulated by rCSE compared to aCSE significantly (p < 0.05). This makes the rCSE have promising biological activity as a candidate for functional food development and/or treatment agent in combating free radicals that cause the aging process. In vivo studies and human trials are certainly needed to see the further efficacy of the rCSE in the future.
WCx-Supported RuNi Single Atoms for Electrocatalytic Oxygen Evolution
Authors: Bai Jirong , Deng Yaoyao , Lian Yuebin , Zhou Quanfa , Zhang Chunyong , Su Yaqiong
Published: October 2023

Single-atom catalysts anchored to oxide or carbonaceous substances are typically tightly coordinated by oxygen or heteroatoms, which certainly impact their electronic structure and coordination environment, thereby affecting their catalytic activity. In this study, we prepared a stable oxygen evolution reaction (OER) catalyst on tungsten carbide using a simple pyrolysis method. The unique structure of tungsten carbide allows the atomic RuNi catalytic site to weakly bond to the surface W and C atoms. XRD patterns and HRTEM images of the WCx-RuNi showed the characteristics of phase-pure WC and W2C, and the absence of nanoparticles. Combined with XPS, the atomic dispersion of Ru/Ni in the catalyst was confirmed. The catalyst exhibits excellent catalytic ability, with a low overpotential of 330 mV at 50 mA/cm2 in 1 m KOH solutions, and demonstrates high long-term stability. This high OER activity is ascribed to the synergistic action of metal Ru/Ni atoms with double monomers. The addition of Ni increases the state density of WCx-RuNi near the Fermi level, promoting the adsorption of oxygen-containing intermediates and enhancing electron exchange. The larger proximity of the d band center to the Fermi level suggests a strong interaction between the d electrons and the valence or conduction band, facilitating charge transfer. Our research offers a promising avenue for reasonable utilization of inexpensive and durable WCx carrier-supported metal single-atom catalysts for electrochemical catalysis.
Reductive Transformation of O-, N-, S-Containing Aromatic Compounds under Hydrogen Transfer Conditions: Effect of the Process on the Ni-Based Catalyst
Authors: Nesterov Nikolai S. , Pakharukova Vera P. , Philippov Alexey A. , Prosvirin Igor P. , Shalygin Anton S. , Martyanov Oleg N.
Published: October 2023

The influence of the reaction medium on the surface structure and properties of a Ni-based catalyst used for the reductive transformations of O-, N-, and S-containing aromatic substrates under hydrogen transfer conditions has been studied. The catalysts were characterized by XRD, XPS, and IR spectroscopy and TEM methods before and after the reductive reaction. It has been shown that the conversion of 1-benzothiophene causes irreversible poisoning of the catalyst surface with the formation of the Ni2S3 phase, whereas the conversion of naphthalene, 1-benzofuran, and indole does not cause any phase change of the catalyst at 250 °C. However, after the indole conversion, the catalyst surface remains enriched with N-containing compounds, which are evenly distributed over the surface.
Valorization of Prunus Seed Oils: Fatty Acids Composition and Oxidative Stability
Authors: Rodríguez-Blázquez Sandra , Gómez-Mejía Esther , Rosales-Conrado Noelia , León-González María Eugenia , García-Sánchez Beatriz , Miranda Ruben
Published: October 2023

Prunus fruit seeds are one of the main types of agri-food waste generated worldwide during the processing of fruits to produce jams, juices and preserves. To valorize this by-product, the aim of this work was the nutritional analysis of peach, apricot, plum and cherry seeds using the official AOAC methods, together with the extraction and characterization of the lipid profile of seed oils using GC-FID, as well as the measurement of the antioxidant activity and oxidative stability using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging method. Chemometric tools were required for data evaluation and the obtained results indicated that the main component of seeds were oils (30–38%, w). All seed oils were rich in oleic (C18:1n9c) and linoleic (C18:2n6c) acids and presented heart-healthy lipid indexes. Oil antioxidant activity was estimated in the range IC50 = 20–35 mg·mL−1, and high oxidative stability was observed for all evaluated oils during 1–22 storage days, with the plum seed oil being the most antioxidant and stable over time. Oxidative stability was also positively correlated with oleic acid content and negatively correlated with linoleic acid content. Therefore, this research showed that the four Prunus seed oils present interesting healthy characteristics for their use and potential application in the cosmetic and nutraceutical industries.
Untargeted and Targeted Metabolomics Reveal the Active Peptide of Eupolyphaga sinensis Walker against Hyperlipidemia by Modulating Imbalance in Amino Acid Metabolism
Authors: Li Yanan , Dong Pingping , Dai Long , Wang Shaoping
Published: October 2023

The active peptide (APE) of Eupolyphaga sinensis Walker, which is prepared by bioenzymatic digestion, has significant antihyperlipidemic effects in vivo, but its mechanism of action on hyperlipidemia is not clear. Recent studies on amino acid metabolism suggested a possible link between it and hyperlipidemia. In this study, we first characterized the composition of APE using various methods. Then, the therapeutic effects of APE on hyperlipidemic rats were evaluated, including lipid levels, the inflammatory response, and oxidative stress. Finally, the metabolism-regulating mechanisms of APE on hyperlipidemic rats were analyzed using untargeted and targeted metabolomic approaches. The results showed that APE significantly reduced the accumulation of fat, oxidative stress levels, and serum pro-inflammatory cytokine levels. Untargeted metabolomic analysis showed that the mechanism of the hypolipidemic effect of APE was mainly related to tryptophan metabolism, phenylalanine metabolism, arginine biosynthesis, and purine metabolism. Amino-acid-targeted metabolomic analysis showed that significant differences in the levels of eight amino acids occurred after APE treatment. Among them, the expression of tryptophan, alanine, glutamate, threonine, valine, and phenylalanine was upregulated, and that of arginine and proline was downregulated in APE-treated rats. In addition, APE significantly downregulated the mRNA expression of SREBP-1, SREBP-2, and HMGCR. Taking these points together, we hypothesize that APE ameliorates hyperlipidemia by modulating amino acid metabolism in the metabolome of the serum and feces, mediating the SREBP/HMGCR signaling pathway, and reducing oxidative stress and inflammation levels.
Synthesis, Characterization, and Biosorption of Cu2+ and Pb2+ Ions from an Aqueous Solution Using Biochar Derived from Orange Peels
Authors: Afolabi Felicia Omolara , Musonge Paul
Published: October 2023

In this study, orange peel (OP) biochar was used as a bio-sorbent for the removal of copper and lead from wastewater in single and binary systems. The equilibrium and kinetic studies were conducted at a pH value of 5, which was the maximum adsorption pH value for both metal ions. The equilibrium studies were investigated at a varying initial concentration (10–200 mg/L) with a constant dosage of 0.1 g, while the kinetic studies were conducted at a fixed initial concentration of 200 mg/L with a constant dosage of 1 g/L for both single and binary systems. The maximum adsorption capacity of the orange peel biochar was 28.06 mg/g, 26.83 mg/g, 30.12 mg/g and 27.71 mg/g for single Cu2+, binary Cu2+, single Pb2+ and binary Pb2+ systems, respectively. The Langmuir isotherm model fitted the experimental data, suggesting that adsorption occurred on a monolayer, while the pseudo-second-order model performed well with the kinetic data. The point of zero charge (pHpzc) of the orange peel biochar was found to be 10.03, which revealed that the surface of the bio-sorbent contains basic groups. A Fourier infrared transform (FTIR) spectroscope and scanning electron microscope, coupled with energy dispersive x-ray (SEM-EDX) and x-ray diffraction analyses, were used to determine the functional groups, surface morphology, and inorganic elements present on the surface of the bio-sorbent, respectively. The results obtained have shown that orange peel biochar is efficient for the removal of Cu2+ and Pb2+ ions from an aqueous solution.
Endothelialization of Whey Protein Isolate-Based Scaffolds for Tissue Regeneration
Authors: Genç Hatice , Friedrich Bernhard , Alexiou Christoph , Pietryga Krzysztof , Cicha Iwona , Douglas Timothy E. L.
Published: October 2023

Background: Whey protein isolate (WPI) is a by-product from the dairy industry, whose main component is β-lactoglobulin. Upon heating, WPI forms a hydrogel which can both support controlled drug delivery and enhance the proliferation and osteogenic differentiation of bone-forming cells. This study makes a novel contribution by evaluating the ability of WPI hydrogels to support the growth of endothelial cells, which are essential for vascularization, which in turn is a pre-requisite for bone regeneration. Methods: In this study, the proliferation and antioxidant levels in human umbilical vascular endothelial cells (HUVECs) cultured with WPI supplementation were evaluated using real-time cell analysis and flow cytometry. Further, the attachment and growth of HUVECs seeded on WPI-based hydrogels with different concentrations of WPI (15%, 20%, 30%, 40%) were investigated. Results: Supplementation with WPI did not affect the viability or proliferation of HUVECs monitored with real-time cell analysis. At the highest used concentration of WPI (500 µg/mL), a slight induction of ROS production in HUVECs was detected as compared with control samples, but it was not accompanied by alterations in cellular thiol levels. Regarding WPI-based hydrogels, HUVEC adhered and spread on all samples, showing good metabolic activity. Notably, cell number was highest on samples containing 20% and 30% WPI. Conclusions: The demonstration of the good compatibility of WPI hydrogels with endothelial cells in these experiments is an important step towards promoting the vascularization of hydrogels upon implantation in vivo, which is expected to improve implant outcomes in the future.
Three Innovative Green and High-Throughput Microwell Spectrophotometric Methods for the Quantitation of Ceritinib, a Potent Drug for the Treatment of ALK-Positive Non-Small Cell Lung Cancer: An Application to the Analysis of Capsules and Drug Uniformity Testing
Authors: Abuhejail Reem M. , Alzoman Nourah Z. , Darwish Ibrahim A.
Published: October 2023

Ceritinib (CER) is a potent drug that has been recently approved by the Food and Drug Administration for the treatment of patients with non-small cell lung cancer harboring the anaplastic lymphoma kinase mutation gene. The existing methods for the quality control of CER are very limited and suffer from limited analytical throughput and do not meet the requirements of the green analytical principles. This study presented the first-ever development and validation of three innovative green and high-throughput microwell spectrophotometric methods (MW-SPMs) for the quality control of CER in its dosage form (Zykadia® capsules). These MW-SPMs were based on the formation of colored N-vinylamino-substituted haloquinone derivatives of CER upon its reactions with each of chloranil, bromanil, and 2,3-dichloro-1,4-naphthoquinone in the presence of acetaldehyde. The optimized procedures of the MW-SPMs were established, and their analytical performances were validated according to the ICH. The linear range of the MW-SPMs was 5–150 µg/mL, with limits of quantitation of 5.3–7.6 µg/mL. The accuracy and precision of the MW-SPMs were proved, as the average recovery values were 99.9–101.0%, and the relative standard deviations did not exceed 1.8%. The three methods were applied to the determination of CER content in Zykadia® capsules and drug content uniformity testing. The greenness of the MW-SPMs was proved using three different metric tools. In addition, these methods encompassed the advantage of high-throughput analysis. In conclusion, the three methods are valuable tools for convenient and reliable application in the pharmaceutical quality control units for CER-containing capsules.
Novel Strigolactone Mimics That Modulate Photosynthesis and Biomass Accumulation in Chlorella sorokiniana
Authors: Popa Daria Gabriela , Georgescu Florentina , Dumitrascu Florea , Shova Sergiu , Constantinescu-Aruxandei Diana , Draghici Constantin , Vladulescu Lucian , Oancea Florin
Published: October 2023

In terrestrial plants, strigolactones act as multifunctional endo- and exo-signals. On microalgae, the strigolactones determine akin effects: induce symbiosis formation with fungi and bacteria and enhance photosynthesis efficiency and accumulation of biomass. This work aims to synthesize and identify strigolactone mimics that promote photosynthesis and biomass accumulation in microalgae with biotechnological potential. Novel strigolactone mimics easily accessible in significant amounts were prepared and fully characterized. The first two novel compounds contain 3,5-disubstituted aryloxy moieties connected to the bioactive furan-2-one ring. In the second group of compounds, a benzothiazole ring is connected directly through the cyclic nitrogen atom to the bioactive furan-2-one ring. The novel strigolactone mimics were tested on Chlorella sorokiniana NIVA-CHL 176. All tested strigolactones increased the accumulation of chlorophyll b in microalgae biomass. The SL-F3 mimic, 3-(4-methyl-5-oxo-2,5-dihydrofuran-2-yl)-3H-benzothiazol-2-one (7), proved the most efficient. This compound, applied at a concentration of 10−7 M, determined a significant biomass accumulation, higher by more than 15% compared to untreated control, and improved the quantum yield efficiency of photosystem II. SL-F2 mimic, 5-(3,5-dibromophenoxy)-3-methyl-5H-furan-2-one (4), applied at a concentration of 10−9 M, improved protein production and slightly stimulated biomass accumulation. Potential utilization of the new strigolactone mimics as microalgae biostimulants is discussed.
Exploring the Sequential-Selective Supercritical Fluid Extraction (S3FE) of Flavonoids and Esterified Triterpenoids from Calendula officinalis L. Flowers
Authors: Atwi-Ghaddar Sirine , Zerwette Lydie , Destandau Emilie , Lesellier Eric
Published: October 2023

One of the many advantages of supercritical fluid extraction (SFE) is the possibility of using it in sequential and selective approaches. This is due to the use of a dynamic extraction mode in addition to the possibility of altering the composition of the modifier during the extraction process. In this study, the optimization of Calendula officinalis L. extraction of non-polar and polar compounds was achieved using three-level Box-Behnken designs (BBD). For non-polar compounds, the factors were pressure, temperature, and EtOH percentage. As for the polar compounds, the three variables were temperature, the total modifier percentage, and H2O added in the modifier as an additive. The recovery of selectively rich extracts in triterpendiol esters and narcissin was possible using a sequential two-step SFE. The first step was performed at 80 °C and 15% EtOH, and the second at 40 °C and 30% EtOH:H2O 80:20 v:v with a total of 60 min of extraction. Additionally, the SFE extraction of non-polar compounds was scaled up on a pilot-scale extractor, demonstrating similar results. Finally, the SFE results were compared to ultrasound-assisted extraction (UAE).
Advances and Prospects in Understanding Vertebrate Cardiac Conduction System, Pacemaker Cell, and Cardiac Muscle Development: Toward Novel Biological Therapies
Authors: Bello Ridwan Opeyemi , Frew Shannon , Siddiqui Yusra , Minhas Rashid
Published: October 2023

The heart is composed of muscle cells called cardiomyocytes, including a specialized population named pacemaker cells that form the cardiac conduction system (CCS), which is responsible for generating the action potential dictating heart contractions. Failure of the CCS system leads to cardiac arrhythmias, which require complicated therapies and often the surgical implantation of electrical pacemakers. However, recent research has focused on the development of novel therapies using biological pacemakers that aim to substitute electrical devices. While most signaling pathways and transcription factors involved in the development of the pacemaker cells are known, the upstream regulatory networks need to be predicted through computer-based databases, mathematical modeling, as well as the functional testing of the regulatory elements in vivo, indicating the need for further research. Here, we summarize the current knowledge about the vertebrate myocardial CCS system and the development of the pacemaker cells, as well as emphasize the areas of future research to clarify the regulation of muscle pacemaker cells and the ease of development of biological therapies.
Oxaliplatin Enhances the Apoptotic Effect of Mesenchymal Stem Cells, Delivering Soluble TRAIL in Chemoresistant Colorectal Cancer
Authors: Quiroz-Reyes Adriana G , Delgado-González Paulina , Islas José F. , Soto-Domínguez Adolfo , González-Villarreal Carlos A. , Padilla-Rivas Gerardo R. , Garza-Treviño Elsa N.
Published: October 2023

A key problem in colorectal cancer (CRC) is the development of resistance to current therapies due to the presence of cancer stem cells (CSC), which leads to poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein that activates apoptosis in cancer cells through union with TRAIL death receptors. Cell therapies as delivery systems can produce soluble TRAIL (sTRAIL) and full-length TRAIL (flTRAIL), showing a high capacity to produce apoptosis in vitro and in vivo assays. However, the apoptotic activity of TRAIL as monotherapy had limitations, so it is important to explore other ways to enhance susceptibility to TRAIL. This study evaluated the cytotoxic and proapoptotic activity of soluble TRAIL overexpressed by mesenchymal stem cells (MSC) in an oxaliplatin-resistant CRC cell line. Bone marrow-MSC were lentiviral transduced for soluble TRAIL expression. DR5 death receptor expression was determined in Caco-2 and CMT-93 CRC cell lines. Sensitivity to first-line chemotherapies and recombinant TRAIL was evaluated by half-maximal inhibitory concentrations. Cytotoxic and proapoptotic activity of soluble TRAIL-MSC alone and combined with chemotherapy pre-treatment was evaluated using co-cultures. Caco-2 and CMT-93 cell lines expressed 59.08 ± 5.071 and 51.65 ± 11.99 of DR5 receptor and had IC50 of 534.15 ng/mL and 581.34 ng/mL for recombinant murine TRAIL (rmTRAIL), respectively. This finding was classified as moderate resistance to TRAIL. The Caco-2 cell line showed resistance to oxaliplatin and irinotecan. MSC successfully overexpressed soluble TRAIL and induced cancer cell death at a 1:6 ratio in co-culture. Oxaliplatin pre-treatment in the Caco-2 cell line increased the cell death percentage (50%) and apoptosis by sTRAIL. This finding was statistically different from the negative control (p < 0.05), and activity was even higher with the oxaliplatin–flTRAIL combination. Thus, oxaliplatin increases apoptotic activity induced by soluble TRAIL in a chemoresistant CRC cell line.
Dendritic Glycerol-Cholesterol Amphiphiles as Drug Delivery Systems: A Comparison between Monomeric and Polymeric Structures
Authors: Romero Jocelyn Fernanda , Herziger Svenja , Cherri Mariam , Dimde Mathias , Achazi Katharina , Mohammadifar Ehsan , Haag Rainer
Published: October 2023

The application of micelles as drug delivery systems has gained a great deal of attention as a means to overcome the current several drawbacks present in conventional cancer treatments. In this work, we highlight the comparison of polymeric and monomeric amphiphilic systems with a similar hydrophilic–lipophilic balance (HLB) in terms of their biocompatibility, aggregation behavior in aqueous solution, and potential in solubilizing hydrophobic compounds. The polymeric system consists of non-ionic polymeric amphiphiles synthesized via sequential RAFT polymerization of polyglycerol first-generation [G1] dendron methacrylate and cholesterol methacrylate to obtain poly(G1-polyglycerol dendron methacrylate)-block-poly(cholesterol methacrylate) (pG1MA-b-pCMA). The monomeric system is a polyglycerol second-generation [G2] dendron end-capped to a cholesterol unit. Both amphiphiles form spherical micellar aggregations in aqueous solution, with differences in size and the morphology in which hydrophobic molecules can be encapsulated. The polymeric and monomeric micelles showed a low critical micelle concentration (CMC) of 0.2 and 17 μg/mL, respectively. The results of our cytotoxicity assays showed that the polymeric system has significantly higher cell viability compared to that of the monomeric amphiphiles. The polymeric micelles were implemented as drug delivery systems by encapsulation of the hydrophobic small molecule doxorubicin, achieving a loading capacity of 4%. In summary, the results of this study reveal that using cholesterol as a building block for polymer synthesis is a promising method of preparation for efficient drug delivery systems while improving the cell viability of monomeric cholesterol.
Empowering Sustainable Growth and Workforce: Unveiling Challenges and Strategies for Retaining Community Pharmacists in Malaysia
Authors: Ooi Khim Lynn , Rajiah Kingston , Maharajan Mari Kannan , Wong Pe Sei
Published: October 2023

Background: Community pharmacists face challenges in job retention due to compensation, work–life balance, and career growth concerns. With pharmacists’ evolving roles in healthcare, retaining them becomes crucial for maintaining quality service. Addressing their needs is vital for a skilled healthcare workforce. This study evaluates job retention among community pharmacists, considering various workforce management domains and demographic characteristics. Materials and Methods: A cross-sectional study was employed with a self-administered questionnaire among community pharmacists in Kuala Lumpur and Selangor, Malaysia. Spearman’s correlations and ordinal logistic regression analysed job retention relationships with workforce domains and predicted the demographic characteristics. Results: A total of 414 participants attempted the survey, of which 311 completed the study. Strong correlations linked job retention with value, trust, and work–life balance. Female pharmacists had higher retention odds, while younger pharmacists had lower retention odds. Pharmacists with over 10 years of experience showed higher retention odds. Discussion: ‘Value and trust’ and ‘work–life balance’ were pivotal for the job retention of community pharmacists. Strategies boosting value, trust, and work–life balance was vital. Gender, age, and experience also predicted job retention. Conclusions: Cultivating trust, valuing contributions, and providing a work–life balance can enhance job retention and commitment.
Quantitative Evaluation of Biomechanical Properties of the Tongue Using a Shaker-Based Optical Coherence Elastography System
Authors: Zhang Yubao , Luo Jiahui , Han Xiao , Shi Gang , Zhang Qin , He Xingdao
Published: October 2023

Biomechanical properties of the tongue play a significant role in maintaining its normal physiological state. Although some techniques have been used to evaluate the tongue’s elasticity, they are limited in clinical detection because of low-resolution and invasive injuries. Here, a shaker-based optical coherence elastography technique that possesses features of high resolution, high sensitivity, and non-destructive imaging was designed and applied to the elastic detection of the tongue for the first time. Repeated experiments were conducted on the in vivo beagle tongue whose shear modulus and Young’s modulus were quantified by visualization of the shear wave propagation, which indicates that our technique is reliable and operable, and may be potentially utilized in clinical fields with further refinement.
An Improvement of the Cherenkov THz Generation Scheme Using Convex Silicon Prism-Lens Adapters
Authors: Kitaeva Galiya Kh. , Safronenkov Daniil A. , Starkova Natalia V.
Published: October 2023

The terahertz (THz) generation efficiency in the Cherenkov optical rectification scheme can be improved significantly if the silicon adaptor, mounted at the lateral surface of a nonlinear crystal, has a convex output surface with proper geometry. We demonstrate and compare with the results of direct experiments a method for theoretically modeling the angular distributions of the spectral power of THz radiation in the case of different Si adaptors, constructed by mounting plano-spherical lenses on a conventional flat Si prism. The applied method of theoretical modeling shows its usefulness in choosing the best Si adapter geometry.