bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermediate Encoding Layers for the Generative Design of 2D Soft Robot Actuators: A Comparison of CPPN’s, L-Systems and Random Generation
Authors: Venter Martin Philip , Conradie Naudé Thomas
Published: May 2023

This paper introduced a comparison method for three explicitly defined intermediate encoding methods in generative design for two-dimensional soft robotic units. This study evaluates a conventional genetic algorithm with full access to removing elements from the design domain using an implicit random encoding layer, a Lindenmayer system encoding mimicking biological growth patterns and a compositional pattern producing network encoding for 2D pattern generation. The objective of the optimisation problem is to match the deformation of a single actuator unit with a desired target shape, specifically uni-axial elongation, under internal pressure. The study results suggest that the Lindenmayer system encoding generates candidate units with fewer function evaluations than the traditional implicitly encoded genetic algorithm. However, the distribution of constraint and internal energy is similar to that of the random encoding, and the Lindenmayer system encoding produces a less diverse population of candidate units. In contrast, despite requiring more function evaluations than the Lindenmayer System encoding, the Compositional Pattern Producing Network encoding produces a similar diversity of candidate units. Overall, the Compositional Pattern Producing Network encoding results in a proportionally higher number of high-performing units than the random or Lindenmayer system encoding, making it a viable alternative to a conventional monolithic approach. The results suggest that the compositional pattern producing network encoding may be a promising approach for designing soft robotic actuators with desirable performance characteristics.
New Insights into the Mechanism of Ulva pertusa on Colitis in Mice: Modulation of the Pain and Immune System
Authors: Ardizzone Alessio , Mannino Deborah , Capra Anna Paola , Repici Alberto , Filippone Alessia , Esposito Emanuela , Campolo Michela
Published: May 2023

Inflammatory bowel diseases (IBDs) involving Crohn’s disease (CD) and ulcerative colitis (UC) are gastrointestinal (GI) disorders in which abdominal pain, discomfort, and diarrhea are the major symptoms. The immune system plays an important role in the pathogenesis of IBD and, as indicated by several clinical studies, both innate and adaptative immune response has the faculty to induce gut inflammation in UC patients. An inappropriate mucosal immune response to normal intestinal constituents is a main feature of UC, thus leading to an imbalance in local pro- and anti-inflammatory species. Ulva pertusa, a marine green alga, is known for its important biological properties, which could represent a source of beneficial effects in various human pathologies. We have already demonstrated the anti-inflammatory, antioxidant, and antiapoptotic effects of an Ulva pertusa extract in a murine model of colitis. In this study, we aimed to examine thoroughly Ulva pertusa immunomodulatory and pain-relieving properties. Colitis was induced by using the DNBS model (4 mg in 100 μL of 50% ethanol), whereas Ulva pertusa was administered daily at the dosage of 50 and 100 mg/kg by oral gavage. Ulva pertusa treatments have been shown to relieve abdominal pain while modulating innate and adaptative immune-inflammatory responses. This powerful immunomodulatory activity was specifically linked with TLR4 and NLRP3 inflammasome modulation. In conclusion, our data suggest Ulva pertusa as a valid approach to counteract immune dysregulation and abdominal discomfort in IBD.
Marfan Syndrome beyond Aortic Root—Phenotyping Using Cardiovascular Magnetic Resonance Imaging and Clinical Implications
Authors: Nyktari Evangelia , Drakopoulou Maria , Rozos Panagiotis , Loukopoulou Sofia , Vrachliotis Thomas , Kourtidou Soultana , Toutouzas Konstantinos
Published: May 2023

Marfan syndrome (MFS) is an inherited autosomal-dominant connective tissue disorder with multiorgan involvement including musculoskeletal, respiratory, cardiovascular, ocular, and skin manifestations. Life expectancy in patients with MFS is primarily determined by the degree of cardiovascular involvement. Aortic disease is the major cardiovascular manifestation of MFS. However, non-aortic cardiac diseases, such as impaired myocardial function and arrhythmia, have been increasingly acknowledged as additional causes of morbidity and mortality. We present two cases demonstrating the phenotypical variation in patients with MFS and how CMR (Cardiovascular Magnetic Resonance) could serve as a “one stop shop” to retrieveS all the necessary information regarding aortic/vascular pathology as well as any potential underlying arrhythmogenic substrate or cardiomyopathic process.
The Effectiveness of Healthcare System Resilience during the COVID-19 Pandemic: A Case Study
Authors: Borzuchowska Monika , Kilańska Dorota , Kozłowski Remigiusz , Iltchev Petre , Czapla Tomasz , Marczewska Sylwia , Marczak Michał
Published: May 2023

Introduction: The outbreak of the COVID-19 pandemic was a period of uncertainty and stress for healthcare managers due to the lack of knowledge (about the transmission of the virus, etc.) and also due to the lack of uniform organisational and treatment procedures. It was a period where the ability to prepare for a crisis, to adapt to the existing conditions, and to draw conclusions from the situation were of critical importance to keep ICUs (intensive care units) operating. The aim of this project is to compare the pandemic response to COVID-19 in Poland during the first and second waves of the pandemic. This comparison will be used to identify the strengths and weaknesses of the response, including challenges presented to health professionals and health systems and ICUs with COVID-19 patients according to the European Union Resilience Model (2014) and the WHO Resilience Model (2020). The WHO Resilience model was suitable to the COVID-19 situation because it was developed based on this experience. Methods: A matrix of 6 elements and 13 standards assigned to them was created using the EC and WHO resilience guidelines. Results: Good governance in resilient systems ensures access to all resources without constraints, free and transparent flow of information, and a sufficient number of well-motivated human resources. Conclusions: Appropriate preparation, adaptation to the existing situation, and effective management of crisis situations are important elements of ensuring the resilience of ICUs.
Relationship of Internal Stress Fields with Self-Organization Processes in Hadfield Steel under Tensile Load
Authors: Popova Natalyi , Slobodyan Mikhail , Klopotov Anatoliy , Nikonenko Elena , Potekaev Alexander , Borodin Vladislav
Published: May 2023

The effect of tensile strains on the microstructure of Hadfield steel was studied by transmission electron microscopy (TEM). Stages of the obtained stress–strain curves were observed, and correlated well with the evolution of the dislocation substructure. Based on an analysis of TEM images, quantitative parameters were determined, such as the material volume fractions, in which slip and twinning occurred, as well as twinning, which developed in one, two and three systems. Some transformation mechanisms were reported that caused great hardening of Hadfield steel. In particular, a complex defect substructure formed in a self-organized manner due to the formation of cells, the dislocations retarded by their walls, as well as the deceleration of dislocations on twins and, vice versa, of twins on dislocations. These factors affected both the average and excess local density of dislocations. Additionally, they resulted in elastic stress fields, which manifested themselves in the curvature–torsion gradient of the crystal lattice. A high level of stresses caused by solid-solution strengthening prevented the relaxation of elastic ones, contributing to the strain hardening of the Hadfield steel.
Design and Fabrication of a High-Temperature SOI Pressure Sensor with Optimized Crossbeam Membrane
Authors: Hao Le , Li Cun , Wang Lukang , Bai Bing , Zhao Yulong , Luo Chao
Published: May 2023

This paper presents a SOI piezoresistive pressure sensor with the crossbeam membrane. The roots of the crossbeam were widened, which solved the problem of the poor dynamic performance of small-range pressure sensors working at a high temperature of 200 °C. A theoretical model was established to optimize the proposed structure, which combined the finite element and the curve fitting. Using the theoretical model, the structural dimensions were optimized to obtain the optimal sensitivity. During optimization, the sensor nonlinearity was also taken into consideration. The sensor chip was fabricated by MEMS bulk-micromachining technology, and Ti/Pt/Au metal leads were prepared to improve the sensor ability of high-temperature resistance over a long time. The sensor chip was packaged and tested, and the experimental results show the sensor achieved an accuracy of 0.241% FS, nonlinearity of 0.180% FS, hysteresis of 0.086% FS and repeatability of 0.137% FS at the high temperature. Given the good reliability and performance at the high temperature, the proposed sensor provides a suitable alternative for the measurement of pressure at high temperatures.
Natural Convection of Ternary Hybrid Nanofluid in a Differential-Heated Enclosure with Non-Uniform Heating Wall
Authors: Rajesh Vemula , Sheremet Mikhail
Published: May 2023

In the field of convective energy transfer, natural convection is one of the most studied phenomena, with applications ranging from heat exchangers and geothermal energy systems to hybrid nanofluids. The aim of this paper is to scrutinize the free convection of a ternary hybrid nanosuspension (Al2O3-Ag-CuO/water ternary hybrid nanofluid) in an enclosure with a linearly warming side border. The ternary hybrid nanosuspension motion and energy transfer have been modelled by partial differential equations (PDEs) with appropriate boundary conditions by the single-phase nanofluid model with the Boussinesq approximation. The finite element approach is applied to resolve the control PDEs after transforming them into a dimensionless view. The impact of significant characteristics such as the nanoparticles’ volume fraction, Rayleigh number, and linearly heating temperature constant on the flow and thermal patterns combined with the Nusselt number has been investigated and analyzed using streamlines, isotherms, and other suitable patterns. The performed analysis has shown that the addition of a third kind of nanomaterial allows for intensifying the energy transport within the closed cavity. The transition between uniform heating to non-uniform heating of the left vertical wall characterizes the heat transfer degradation due to a reduction of the heat energy output from this heated wall.
Prospectivity Mapping of Tungsten Mineralization in Southern Jiangxi Province Using Few-Shot Learning
Authors: Zhou Kai , Sun Tao , Liu Yue , Feng Mei , Tang Jialiang , Mao Luting , Pu Wenbin , Huang Junqi
Published: May 2023

The development of mineral prospectivity mapping (MPM), which aims to outline and prioritize mineral exploration targets, has been spurred by advances in data-driven machine learning algorithms. Supervised data-driven MPM is a typical few-shot task, suffering from a scarcity of labeled data, the over-fitting of models and an uncertainty of predictions. The main objective of this contribution is to propose a robust framework of few-shot learning (FSL), combining data augmentation and transfer learning to enable the generation of prospectivity models with excellent predictive efficiency and low uncertainty. The mineral systems approach was used to transfer a conceptual mineral system into mappable exploration criteria. Synthetic minority over-sampling technique (SMOTE) was employed to augment and balance the labeled dataset, allowing for model pre-training with the large synthetic training dataset of a source domain. The knowledge derived from pre-trained models was then transferred to the target domain by fine-tuning, and the prospectivity model was generated in light of over-fitting and uncertainty assessments. The proposed FSL framework was applied to tungsten prospectivity mapping in southern Jiangxi Province. The results indicated that the SMOTE-ed balanced dataset boosted the classification accuracy in the training process. The FSL models yielded an arch-shaped prediction point pattern which was favorable for focusing potential targets with high probability and low uncertainty. The FSL models achieved a high predictive performance (test AUC = 0.9172) and the lowest quantitative over-fitting value compared to the models derived from the benchmark algorithms of random forest and support vector machine. Four levels of potential targeting zones, considering both predictive efficiency and uncertainty, were extracted from the resulting FSL prospectivity map. The final high-potential and low-risk exploration targets only cover 4.27% of the area, but capture 41.53% of known tungsten deposits, thus achieving a superior predictive performance. This study highlights the capability of FSL framework to control over-fitting and generate high-confidence exploration targets with low levels of uncertainty.
Red-Emitting Carbon Quantum Dots for Biomedical Applications: Synthesis and Purification Issues of the Hydrothermal Approach
Authors: La Ferla Barbara , Vercelli Barbara
Published: May 2023

The possibility of performing the synthesis of red-emitting carbon quantum dots (r-CDs), in a well-controllable, large scale and environmentally sustainable way is undoubtedly of fundamental importance, as it will pave the way to their employment in advanced medical large-scale applications. Knowledge of the difficulties involved in producing r-CDs with reproducible optical, structural, and chemical characteristics, might help in their large-scale production, making the process standardizable. In this work, we present an experimental study, also supported by results reported in the literature, on the issues encountered during the synthesis and post-synthesis purification treatments of r-CDS. We focused on the hydrothermal approach as it was found to be more suitable for future large-scale industrial applications. We propose three synthetic strategies and observed that employing p-phenylenediamine (p-PDA), as a precursor, the synthetic process showed low efficiency with low yields of r-CDs, large amounts of unreacted precursor, and reaction intermediates. Changing reaction parameters does not improve performance. The r-CDs obtained using citric acid (CA) and urea, as precursors, resulted to be sensitive to pH and difficult to separate from the reaction mixture. Furthermore, the proposed synthetic strategies show that the hydrothermal preparation of r-CDS requires approaches that are not fully sustainable.
Impact of Maternal Lifestyle and Dietary Habits during Pregnancy on Newborn Metabolic Profile
Authors: Cicalini Ilaria , Moffa Samanta , Tommolini Maria Lucia , Valentinuzzi Silvia , Zucchelli Mirco , Bucci Ines , Chiacchiaretta Piero , Fontana Antonella , Federici Luca , De Laurenzi Vincenzo , Del Boccio Piero , Rossi Claudia , Pieragostino Damiana
Published: May 2023

Expanded newborn screening (NBS) is a preventive program that allows for the early identification of over 40 congenital endocrine-metabolic diseases by analyzing dried blood spot samples collected from the newborn’s heel within 48–72 h of birth. The determination of amino acids and acyl-carnitines by Flow Injection Analysis Tandem Mass Spectrometry (FIA-MS/MS) may also highlight metabolic alterations resulting from external factors, such as maternal nutrition. In the present study, we developed a questionnaire to investigate the eating habits of 109 women during pregnancy and statistically correlated the results from the investigation on dietary habits with the data obtained by the NBS laboratory of Abruzzo region (Italy). Parameters such as smoking, physical activity, and the intake of iodized salt, drugs, and supplements were analyzed. This study aimed to highlight how maternal lifestyle, diet, and drug intake during pregnancy may affect the neonatal metabolic profile, possibly generating false positive or false negative results in the NBS test. The results pointed out how the knowledge of maternal nutrition and lifestyle may also be precious in preventing misinterpretations of the neonatal metabolic profile, thereby reducing unnecessary stress for newborns and their parents and limiting costs for the health system.
Knowledge and Beliefs about Herb/Supplement Consumption and Herb/Supplement–Drug Interactions among the General Population, including Healthcare Professionals and Pharmacists: A Systematic Review and Guidelines for a Smart Decision System
Authors: Dores Artemisa R. , Peixoto Miguel , Castro Maria , Sá Catarina , Carvalho Irene P. , Martins Andreia , Maia Eva , Praça Isabel , Marques António
Published: May 2023

The increased consumption of a variety of herbs/supplements has been raising serious health concerns. Owing to an inadequate understanding of herb/supplement–drug interactions, the simultaneous consumption of these products may result in deleterious effects and, in extreme cases, even fatal outcomes. This systematic review is aimed at understanding the knowledge and beliefs about the consumption of herbs/supplements and herb/drug–supplement interactions (HDIs). The study follows the PRISMA guidelines. Four online databases (Web of Science; PubMed; Cochrane; and EBSCOhost) were searched, and a total of 44 studies were included, encompassing 16,929 participants. Herb and supplement consumption is explained mostly by the reported benefits across multiple conditions and ease of use. Regarding HDIs, most people take both herbs/supplements and prescription drugs simultaneously. Only a small percentage of participants have knowledge about their interaction effects, and many reported adverse interactions or side effects. Nevertheless, the main reason for stopping the prescribed drug intake is the perceived lack of its effect, and not due to interactions. Therefore, it is important to increase the knowledge about supplement use so that further strategies can be elaborated to better detect or be alert for whenever a potentially dangerous reaction and/or interaction may occur. This paper raises awareness regarding the need for developing a decision support system and ends with some considerations about the development of a technological solution capable of detecting HDIs and, thereby, aiding in the improvement of pharmacy services.
Prevalence of Obesity and the Factors Associated with Low Obesity Awareness among Urban Adolescents in Harare, Zimbabwe
Authors: Pencil Ashleigh , Matsungo Tonderayi M. , Hongu Nobuko , Hayami Naomi
Published: May 2023

Obesity is a global health problem. In developing countries such as Zimbabwe, obesity is both an emerging health problem and a grey area, particularly among adolescents. This study assessed the prevalence of obesity and factors associated with low obesity awareness among adolescents. Method: A cross-sectional survey was performed using an interviewer-administered questionnaire. The participants were 423 adolescents aged 14–19 years recruited from 10 schools in Harare using a stratified random sampling technique. Data were analyzed using SPSS software (version 23) and binary logistics regression was used to examine the factors associated with low obesity awareness. The level of significance was set at p < 0.05. Results: The median± IQR age was 16 (14-18) years, and overweight and obesity affected 15.8% of the participants with higher proportions among girls (73.1%, p = 0.002). Low obesity awareness was observed in 27.1% of the adolescents with a higher proportion among girls (67.0%, p = 0.001), 14–16-year-olds (51.3%, p = 0.317), and obese adolescents (56.7%, p = 0.001). Significant factors associated with low obesity awareness were household heads lacking formal education [OR = 9.41 (2.20–40.36), p = 0.003] and inadequate (poor) food habits [OR = 2.58 (1.33–5.01), p = 0.005]. Conclusions: Our study showed that adolescents had different obesity awareness levels and diverse perceptions in terms of obesity causes, and a range of potential solutions. Obesity awareness and nutrition education should address adolescents’ poor eating habits while taking cognizance of the different education levels of household heads.
Association of Macronutrients Intake with Body Composition and Sarcopenic Obesity in Children and Adolescents: A Population-Based Analysis of the National Health and Nutrition Examination Survey (NHANES) 2011–2018
Authors: Yang Bing , Tang Chengjun , Shi Zumin , Gao Liwang
Published: May 2023

The association of macronutrients intake with body composition and sarcopenic obesity remains uncertain in children and adolescents. We aimed to explore the association between macronutrients intake and body composition, especially sarcopenic obesity, in children and adolescents residing in the United States. The study utilized data from 5412 participants aged 6–17 years who attended NHANES between 2011 and 2018. Body composition was assessed using DXA, and nutrient intake was based on 24-h recall. Multivariable linear regression and multinomial logistic regression were used. The unweighted prevalence of sarcopenic obesity was 15.6%. A higher percentage of energy (5 %E) from fat was inversely associated with muscle mass but positively associated with fat mass and sarcopenic obesity. Substituting carbohydrate (5 %E) with fat decreased muscle mass by 0.03 (95% CI 0.01 to 0.06) but increased fat mass by 0.03 (95% CI 0.01 to 0.06) and increased the prevalence of sarcopenic obesity by 254% (95% CI 15% to 487%). Replacing protein intake with fat intake also increased the OR of sarcopenic obesity (OR, 2.36 [95% CI 1.18 to 3.18]). In conclusion, a high-fat diet, coupled with low carbohydrate/protein intake, is associated with sarcopenic obesity among children and adolescents. The change in children’s diet towards a healthy diet with low fat composition may help prevent sarcopenic obesity. However, randomized clinical trials or longitudinal studies are needed to further validate our findings.
Beneficial Effects of Daily Consumption of Garlic and Onion Extract Concentrate on Infectious Respiratory Diseases in Elderly Resident Volunteers
Authors: García-García Jorge , Gracián Carlos , Baños Alberto , Guillamón Enrique , Gálvez Julio , Rodriguez-Nogales Alba , Fonollá Juristo
Published: May 2023

Aging is a biological process with high susceptibility to several infections. This risk increases in older patients in residential care facilities (RCF). Thus, there is a clear demand for developing preventive interventions with new therapeutic compounds that combine efficacy and safety. This could be the case of compounds derived from plants of the genus Allium spp. The purpose of this study was to evaluate the impact of a combination of a garlic and onion extract concentrate standardized in organosulfur compounds derived from propiin on the incidence of respiratory tract infections in elderly patients of RCF. Sixty-five volunteers were selected at random to receive a placebo or a single daily dose of the extract for thirty-six weeks. Different clinical visits were performed to evaluate the main respiratory diseases with an infectious origin, as well as the associated symptoms and their duration. The extract showed a clinical safety profile and significantly reduced the incidence of respiratory infections. Moreover, the treatment decreased the number and duration of the associated symptoms compared with the placebo group. For the first time, we demonstrated the protective effect of Alliaceae extract in respiratory infectious diseases in elderly healthy volunteers, which could be used prophylactically against the most common infectious respiratory diseases.
Morphologic and Genetic Analysis of Synhimantus (Synhimantus) laticeps from a Long-Eared Owl (Asio otus)
Authors: Lopes Carolina , Santos-Silva Sérgio , Nunes Carolina , Mendes Susana , Costa Catarina , Brazio Erica , Coutinho Teresa , Rodrigues Filipa Teixeira , Mesquita João R. , Coelho Ana Cláudia , Cardoso Luís , Lopes Ana Patrícia
Published: May 2023

The long-eared owl (Asio otus) is a medium-sized owl species that is well-distributed in almost all of the territories in Portugal. Nematodes were found in the oral cavity of a long-eared owl (A. otus) admitted to CRASSA (Wildlife Rehabilitation Centre of Santo André). During a physical exam and stabilization of the bird, five nematodes were collected. The worms were examined and measured under light microscopy, and photos were taken. After a morphological analysis was conducted, all the nematodes (five females) were identified as Synhimantus (Synhimantus) laticeps. Two specimens were subjected to molecular analysis, which confirmed the result. This study provides a combined morphological and genetic approach to S. laticeps. To the authors’ best knowledge, this is the first report including genetic sequencing of S. laticeps in a long-eared owl (A. otus) from Portugal.
Neuropharmacological Potential of Diterpenoid Alkaloids
Authors: Salehi Arash , Ghanadian Mustafa , Zolfaghari Behzad , Jassbi Amir Reza , Fattahian Maryam , Reisi Parham , Csupor Dezső , Khan Ikhlas A. , Ali Zulfiqar
Published: May 2023

This study provides a narrative review of diterpenoid alkaloids (DAs), a family of extremely important natural products found predominantly in some species of Aconitum and Delphinium (Ranunculaceae). DAs have long been a focus of research attention due to their numerous intricate structures and diverse biological activities, especially in the central nervous system (CNS). These alkaloids originate through the amination reaction of tetra or pentacyclic diterpenoids, which are classified into three categories and 46 types based on the number of carbon atoms in the backbone structure and structural differences. The main chemical characteristics of DAs are their heterocyclic systems containing β-aminoethanol, methylamine, or ethylamine functionality. Although the role of tertiary nitrogen in ring A and the polycyclic complex structure are of great importance in drug-receptor affinity, in silico studies have emphasized the role of certain sidechains in C13, C14, and C8. DAs showed antiepileptic effects in preclinical studies mostly through Na+ channels. Aconitine (1) and 3-acetyl aconitine (2) can desensitize Na+ channels after persistent activation. Lappaconitine (3), N-deacetyllapaconitine (4), 6-benzoylheteratisine (5), and 1-benzoylnapelline (6) deactivate these channels. Methyllycaconitine (16), mainly found in Delphinium species, possesses an extreme affinity for the binding sites of α7 nicotinic acetylcholine receptors (nAChR) and contributes to a wide range of neurologic functions and the release of neurotransmitters. Several DAs such as bulleyaconitine A (17), (3), and mesaconitine (8) from Aconitum species have a drastic analgesic effect. Among them, compound 17 has been used in China for decades. Their effect is explained by increasing the release of dynorphin A, activating the inhibitory noradrenergic neurons in the β-adrenergic system, and preventing the transmission of pain messages by inactivating the Na+ channels that have been stressed. Acetylcholinesterase inhibitory, neuroprotective, antidepressant, and anxiolytic activities are other CNS effects that have been investigated for certain DAs. However, despite various CNS effects, recent advances in developing new drugs from DAs were insignificant due to their neurotoxicity.
S-72, a Novel Orally Available Tubulin Inhibitor, Overcomes Paclitaxel Resistance via Inactivation of the STING Pathway in Breast Cancer
Authors: Hou Zhenyan , Lin Songwen , Du Tingting , Wang Mingjin , Wang Weida , You Shen , Xue Nina , Liu Yichen , Ji Ming , Xu Heng , Chen Xiaoguang
Published: May 2023

Microtubule-targeting agents are widely used as active anticancer drugs. However, drug resistance always emerges after their long-term use, especially in the case of paclitaxel, which is the cornerstone of all subtypes of breast cancer treatment. Hence, the development of novel agents to overcome this resistance is vital. This study reports on a novel, potent, and orally bioavailable tubulin inhibitor called S-72 and evaluated its preclinical efficacy in combating paclitaxel resistance in breast cancer and the molecular mechanisms behind it. We found that S-72 suppresses the proliferation, invasion and migration of paclitaxel-resistant breast cancer cells in vitro and displays desirable antitumor activities against xenografts in vivo. As a characterized tubulin inhibitor, S-72 typically inhibits tubulin polymerization and further triggers mitosis-phase cell cycle arrest and cell apoptosis, in addition to suppressing STAT3 signaling. Further studies showed that STING signaling is involved in paclitaxel resistance, and S-72 blocks STING activation in paclitaxel-resistant breast cancer cells. This effect further restores multipolar spindle formation and causes deadly chromosomal instability in cells. Our study offers a promising novel microtubule-destabilizing agent for paclitaxel-resistant breast cancer treatment as well as a potential strategy that can be used to improve paclitaxel sensitivity.
Exploring the Molecular Players behind the Potentiation of Chemotherapy Effects by Durvalumab in Lung Adenocarcinoma Cell Lines
Authors: Saar Marika , Jaal Jana , Meltsov Alvin , Laasfeld Tõnis , Lust Helen , Kasvandik Sergo , Lavogina Darja
Published: May 2023

Immune checkpoint inhibitors are increasingly used in combination with chemotherapy for the treatment of non-small cell lung cancer, yet the success of combination therapies is relatively limited. Thus, more detailed insight regarding the tumor molecular markers that may affect the responsiveness of patients to therapy is required. Here, we set out to explore the proteome of two lung adenocarcinoma cell lines (HCC-44 and A549) treated with cisplatin, pemetrexed, durvalumab, and the corresponding mixtures to establish the differences in post-treatment protein expression that can serve as markers of chemosensitivity or resistance. The mass spectrometry study showed that the addition of durvalumab to the treatment mixture resulted in cell line- and chemotherapeutic agent-dependent responses and confirmed the previously reported involvement of DNA repair machinery in the potentiation of the chemotherapy effect. Further validation using immunofluorescence also indicated that the potentiating effect of durvalumab in the case of cisplatin treatment was dependent on the tumor suppressor RB-1 in the PD-L1 weakly positive cells. In addition, we identified aldehyde dehydrogenase ALDH1A3 as the general putative resistance marker. Further studies in patient biopsy samples will be required to confirm the clinical significance of these findings.
Mesenchymal Stromal Cell Exosomes Mediate M2-like Macrophage Polarization through CD73/Ecto-5′-Nucleotidase Activity
Authors: Teo Kristeen Ye Wen , Zhang Shipin , Loh Jia Tong , Lai Ruenn Chai , Hey Hwee Weng Dennis , Lam Kong-Peng , Lim Sai Kiang , Toh Wei Seong
Published: May 2023

Mesenchymal stem/stromal cell (MSC) exosomes have been shown to alleviate immune dysfunction and inflammation in preclinical animal models. This therapeutic effect is attributed, in part, to their ability to promote the polarization of anti-inflammatory M2-like macrophages. One polarization mechanism has been shown to involve the activation of the MyD88-mediated toll-like receptor (TLR) signaling pathway by the presence of extra domain A-fibronectin (EDA-FN) within the MSC exosomes. Here, we uncovered an additional mechanism where MSC exosomes mediate M2-like macrophage polarization through exosomal CD73 activity. Specifically, we observed that polarization of M2-like macrophages by MSC exosomes was abolished in the presence of inhibitors of CD73 activity, adenosine receptors A2A and A2B, and AKT/ERK phosphorylation. These findings suggest that MSC exosomes promote M2-like macrophage polarization by catalyzing the production of adenosine, which then binds to adenosine receptors A2A and A2B to activate AKT/ERK-dependent signaling pathways. Thus, CD73 represents an additional critical attribute of MSC exosomes in mediating M2-like macrophage polarization. These findings have implications for predicting the immunomodulatory potency of MSC exosome preparations.
Development of a Gold Nanoparticle-Linked Immunosorbent Assay of Staphylococcal Enterotoxin B Detection with Extremely High Sensitivity by Determination of Gold Atom Content Using Graphite Furnace Atomic Absorption Spectrometry
Authors: Song Chaojun , Liu Yutao , Hu Jinwei , Zhu Yupu , Ma Zhengjun , Xi Jiayue , Cui Minxuan , Ren Leiqi , Fan Li
Published: May 2023

Highly sensitive staphylococcal enterotoxin B (SEB) assay is of great importance for the prevention of toxic diseases caused by SEB. In this study, we present a gold nanoparticle (AuNP)-linked immunosorbent assay (ALISA) for detecting SEB in a sandwich format using a pair of SEB specific monoclonal antibodies (mAbs) performed in microplates. First, the detection mAb was labeled with AuNPs of different particle sizes (15, 40 and 60 nm). Then the sandwich immunosorbent assay for SEB detection was performed routinely in a microplate except for using AuNPs-labeled detection mAb. Next, the AuNPs adsorbed on the microplate were dissolved with aqua regia and the content of gold atoms was determined by graphite furnace atomic absorption spectrometry (GFAAS). Finally, a standard curve was drawn of the gold atomic content against the corresponding SEB concentration. The detection time of ALISA was about 2.5 h. AuNPs at 60 nm showed the highest sensitivity with an actual measured limit of detection (LOD) of 0.125 pg/mL and a dynamic range of 0.125–32 pg/mL. AuNPs at 40 nm had an actual measured LOD of 0.5 pg/mL and a dynamic range of 0.5 to 128 pg/mL. AuNPs at 15 nm had an actual measured LOD of 5 pg/mL, with a dynamic range of 5–1280 pg/mL. With detection mAb labeled with AuNPs at 60 nm, ALISA’s intra- and interassay coefficient variations (CV) at three concentrations (2, 8, and 20 pg/mL) were all lower than 12% and the average recovery level was ranged from 92.7% to 95.0%, indicating a high precision and accuracy of the ALISA method. Moreover, the ALISA method could be successfully applied to the detection of various food, environmental, and biological samples. Therefore, the successful establishment of the ALISA method for SEB detection might provide a powerful tool for food hygiene supervision, environmental management, and anti-terrorism procedures and this method might achieve detection and high-throughput analysis automatically in the near future, even though GFAAS testing remains costly at present.
Polymers in Engineering Extracellular Vesicle Mimetics: Current Status and Prospective
Authors: Wei Xinyue , Liu Sihang , Cao Yifeng , Wang Zhen , Chen Shengfu
Published: May 2023

The maintenance of a high delivery efficiency by traditional nanomedicines during cancer treatment is a challenging task. As a natural mediator for short-distance intercellular communication, extracellular vesicles (EVs) have garnered significant attention owing to their low immunogenicity and high targeting ability. They can load a variety of major drugs, thus offering immense potential. In order to overcome the limitations of EVs and establish them as an ideal drug delivery system, polymer-engineered extracellular vesicle mimics (EVMs) have been developed and applied in cancer therapy. In this review, we discuss the current status of polymer-based extracellular vesicle mimics in drug delivery, and analyze their structural and functional properties based on the design of an ideal drug carrier. We anticipate that this review will facilitate a deeper understanding of the extracellular vesicular mimetic drug delivery system, and stimulate the progress and advancement of this field.
Phosphatidylglycerol to Treat Chronic Skin Wounds in Diabetes
Authors: Luo Yonghong , Vivaldi Marrero Edymarie , Choudhary Vivek , Bollag Wendy B.
Published: May 2023

This review proposes the use of dioleoylphosphatidylglycerol (DOPG) to enhance diabetic wound healing. Initially, the characteristics of diabetic wounds are examined, focusing on the epidermis. Hyperglycemia accompanying diabetes results in enhanced inflammation and oxidative stress in part through the generation of advanced glycation end-products (AGEs), in which glucose is conjugated to macromolecules. These AGEs activate inflammatory pathways; oxidative stress results from increased reactive oxygen species generation by mitochondria rendered dysfunctional by hyperglycemia. These factors work together to reduce the ability of keratinocytes to restore epidermal integrity, contributing to chronic diabetic wounds. DOPG has a pro-proliferative action on keratinocytes (through an unclear mechanism) and exerts an anti-inflammatory effect on keratinocytes and the innate immune system by inhibiting the activation of Toll-like receptors. DOPG has also been found to enhance macrophage mitochondrial function. Since these DOPG effects would be expected to counteract the increased oxidative stress (attributable in part to mitochondrial dysfunction), decreased keratinocyte proliferation, and enhanced inflammation that characterize chronic diabetic wounds, DOPG may be useful in stimulating wound healing. To date, efficacious therapies to promote the healing of chronic diabetic wounds are largely lacking; thus, DOPG may be added to the armamentarium of drugs to enhance diabetic wound healing.
Novel Biomass-Based Polymeric Dyes: Preparation and Performance Assessment in the Dyeing of Biomass-Derived Aldehyde-Tanned Leather
Authors: Ding Wei , Zhang Yinuo , Li Shuolin , Remón Javier , Wang Kanglei , Bao Lihong , Pang Xiaoyan
Published: May 2023

High-performance chrome-free leather production is currently one of the most concerning needs to warrant the sustainable development of the leather industry due to the serious chrome pollution. Driven by these research challenges, this work explores using biobased polymeric dyes (BPDs) based on dialdehyde starch and reactive small-molecule dye (reactive red 180, RD-180) as novel dyeing agents for leather tanned using a chrome-free, biomass-derived aldehyde tanning agent (BAT). FTIR, 1H NMR, XPS, and UV-visible spectrometry analyses indicated that a Schiff base structure was generated between the aldehyde group of dialdehyde starch (DST) and the amino group of RD-180, resulting in the successful load of RD-180 on DST to produce BPD. The BPD could first penetrate the BAT-tanned leather efficiently and then be deposited on the leather matrix, thus exhibiting a high uptake ratio. Compared with the crust leathers prepared using a conventional anionic dye (CAD), dyeing, and RD-180 dyeing, the BPD-dyed crust leather not only had better coloring uniformity and fastness but it also showed a higher tensile strength, elongation at break, and fullness. These data suggest that BPD has the potential to be used as a novel sustainable polymeric dye for the high-performance dyeing of organically tanned chrome-free leather, which is paramount to ensuring and promoting the sustainable development of the leather industry.
Disordering of Starch Films as a Factor Influencing the Release Rate of Biologically Active Substances
Authors: Podgorbunskikh Ekaterina , Kuskov Timofei , Matveeva Anna , Ulihin Artem , Bychkov Aleksey , Lomovskiy Igor , Polienko Yuliya
Published: May 2023

The release of a spin probe (nitroxide radical) from polymer films was studied by electron paramagnetic resonance (EPR). The films were fabricated from starch having different crystal structures (A-, B-, and C-types) and disordering degrees. Film morphology (analysis of the scanning electron microscopy (SEM)) depended on the presence of dopant (nitroxide radical) to a larger extent rather than on crystal structure ordering or polymorphic modification. The presence of nitroxide radical led to additional crystal structure disordering and reduced the crystallinity index from the X-ray diffraction (XRD) data. Polymeric films made of amorphized starch powder were able to undergo recrystallization (crystal structure rearrangement), which manifested itself as an increase in crystallinity index and phase transition of the A- and C-type crystal structures to the B-type one. It was demonstrated that nitroxide radical does not form an individual phase during film preparation. According to the EPR data, local permittivity of starch-based films varied from 52.5 to 60.1 F/m, while bulk permittivity did not exceed 17 F/m, which demonstrates that local concentration of water is increased in the regions near the nitroxide radical. The mobility of the spin probe corresponds to small stochastic librations and is indicative of the strongly a mobilized state. The application of kinetic models made it possible to find out that substance release from biodegradable films consists of two stages: matrix swelling and spin probe diffusion through the matrix. Investigation of the release kinetics for nitroxide radical demonstrated that the course of this process depends on the type of crystal structure of native starch.
Spatio-Temporal Patterns of NDVI and Its Influencing Factors Based on the ESTARFM in the Loess Plateau of China
Authors: Fan Xinyi , Gao Peng , Tian Biqing , Wu Changxue , Mu Xingmin
Published: May 2023

The Loess Plateau is ecologically vulnerable. Vegetation is the key factor in ecological improvement. The study of the distribution patterns of vegetation and its impact factors has important guiding meaning for ecological construction in the region. The existing single sensor cannot provide long-term and high-resolution data. We established data of NDVI with a great spatial resolution by fusing the GIMMS NDVI and the MODIS NDVI based on the ESTARFM. Furthermore, we analyzed the variation in NDVI under different topographies and its response to climatic factors and human activities in the Loess Plateau. The results manifested that: (1) The fused NDVI by the ESTARFM had a high correlation with the MODIS NDVI and can be used in subsequent studies. (2) The multi-year average NDVI of this region ranged from 0.027 to 0.973, which is specifically low in the northwest and high southeast. The NDVI manifested an upward trend in the last 31 years. Its growth rate was 0.0036/a (p < 0.01). Spatially, the area with an upward trend of NDVI accounted for 89.48% of the plateau. (3) For topography, the larger area with the extremely significant upward of NDVI was found at elevations of 500–1500 m, with slopes of 6–15°. The larger area with the extremely significant downward trend of NDVI was found at an elevation of higher than 3000 m, with a slope of greater than 35°. (4) The response of the NDVI to the climatic factors manifested a significant spatial heterogeneity. The temperature had a more significant impact on NDVI than precipitation. (5) Human activities contributed more to NDVI than climatic factors (65.22% for human activities and 34.78% for climatic factors). Among them, the area with a high contribution of human activities to NDVI increase was consistent with the area where the GGP was implemented. The distribution of areas with high contribution of human activities to NDVI decrease was in line with that of the provincial capital cities. The results served as the theoretical foundation for assessing the efficacy of environmental stewardship and for optimizing ecological restoration measures.
An HMM-DNN-Based System for the Detection and Classification of Low-Frequency Acoustic Signals from Baleen Whales, Earthquakes, and Air Guns off Chile
Authors: Buchan Susannah J. , Duran Miguel , Rojas Constanza , Wuth Jorge , Mahu Rodrigo , Stafford Kathleen M. , Becerra Yoma Nestor
Published: May 2023

Marine passive acoustic monitoring can be used to study biological, geophysical, and anthropogenic phenomena in the ocean. The wide range of characteristics from geophysical, biological, and anthropogenic sounds sources makes the simultaneous automatic detection and classification of these sounds a significant challenge. Here, we propose a single Hidden Markov Model-based system with a Deep Neural Network (HMM-DNN) for the detection and classification of low-frequency biological (baleen whales), geophysical (earthquakes), and anthropogenic (air guns) sounds. Acoustic data were obtained from the Preparatory Commission for the Comprehensive Nuclear-Test-Ban Treaty Organization station off Juan Fernandez, Chile (station HA03) and annotated by an analyst (498 h of audio data containing 30,873 events from 19 different classes), and then divided into training (60%), testing (20%), and tuning (20%) subsets. Each audio frame was represented as an observation vector obtained through a filterbank-based spectral feature extraction procedure. The HMM-DNN training procedure was carried out discriminatively by setting HMM states as targets. A model with Gaussian Mixtures Models and HMM (HMM-GMM) was trained to obtain an initial set of HMM target states. Feature transformation based on Linear Discriminant Analysis and Maximum Likelihood Linear Transform was also incorporated. The HMM-DNN system displayed good capacity for correctly detecting and classifying events, with high event-level accuracy (84.46%), high weighted average sensitivity (84.46%), and high weighted average precision (89.54%). Event-level accuracy increased with higher event signal-to-noise ratios. Event-level metrics per class also showed that our HMM-DNN system generalized well for most classes but performances were best for classes that either had a high number of training exemplars (e.g., generally above 50) and/or were for classes of signals that had low variability in spectral features, duration, and energy levels. Fin whale and Antarctic blue whale song and air guns performed particularly well.
Volume Loss Assessment with MT-InSAR during Tunnel Construction in the City of Naples (Italy)
Authors: Della Ragione Gianluigi , Rocca Alfredo , Perissin Daniele , Bilotta Emilio
Published: May 2023

The construction of tunnels in urban areas can affect the nearby existing infrastructures and buildings, as shallow excavations induce movements up to the ground surface. An important parameter to be monitored during the excavation is the volume loss, which plays a crucial role in determining the ground movements at the surface. InSAR satellite monitoring has the potential to detect ground movements at the millimetric scale on a vast area for tunneling applications. In the present study, the Multi-Temporal InSAR (MT-InSAR) technique, based on the persistent scattering method, is used to retrieve vertical displacements induced by the excavation of twin tunnels of a metro line in the City of Naples (Italy). Here, the volume loss is obtained by fitting a Gaussian curve on the monitored settlement data induced by the excavation of the first tunnel. The latter is then used to predict the settlement of the second excavation about one year later and compared to the MT-InSAR data. These monitored data show the typical shape of the settlement profile, confirming the empirical Gaussian distribution and MT-InSAR capability to detect millimetric displacements. Therefore, MT-InSAR can be used to feed algorithms to improve the prediction of tunneling-induced displacements.