bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying Different Vinification Techniques in Teran Red Wine Production: Impact on Bioactive Compounds and Sensory Attributes
Authors: Orbanić Fumica , Rossi Sara , Bestulić Ena , Budić-Leto Irena , Kovačević Ganić Karin , Horvat Ivana , Plavša Tomislav , Bubola Marijan , Lukić Igor , Jeromel Ana , Radeka Sanja
Published: October 2023

Six different vinification treatments, including a control treatment (7-day standard maceration) (K7), were performed to study the effects of non-standard techniques on bioactive compounds and sensory attributes of Teran red wine. Pre-fermentative mash cooling (8 °C; 48 h) and heating (50 °C; 48 h) followed by prolonged post-fermentative maceration of 13 days (C15;H15) or 28 days (C30;H30) were applied. In another treatment, after cooling, saignée was performed followed by 13-day prolonged maceration (CS15). Wine phenols and vitamins were analyzed by HPLC-DAD-FLD, minerals by ICP-OES, and sensory analysis was performed using the QDA and 100-point O.I.V./U.I.O.E. methods. Obtained results showed total phenolic concentration was the highest in the H30 treatment. The concentration of anthocyanins, flavan-3-ols and phenolic acids was significantly higher in wines of all vinification techniques compared to the control. Stilbene content was highly affected by pre-fermentative heating. Treatments CS15, H15, C30 and H30 resulted in the highest scores by both the QDA and 100-point sensory methods. The obtained results suggest that advanced non-standard vinification techniques have a significant impact on Teran wine by enhancing its composition of bioactive compounds and improving its sensory profile, which gives it an additional market value. Furthermore, a comprehensive comparison of such techniques applied simultaneously in one study is of substantial importance for additional research in wine production.
Spilanthes acmella Extract-Based Natural Oils Loaded Emulgel for Anti-Microbial Action against Dermatitis
Authors: Afzal Aqsa , Shah Syed Nisar Hussain , Javed Hina , Mumtaz Asma , Saeed Javeria , Rasheed Hafiz Majid , Arshad Rabia , Ansari Siddique Akber , Alkahtani Hamad M. , Ansari Irfan Aamer
Published: October 2023

Background: Dermatitis is skin disorder that is complicated by recurrent infections of skin by bacteria, viruses, and fungi. Spilanthol is an active constituent of Spilanthes acmella, which possess strong anti-bacterial properties. The purpose of this study was to develop a herbal emulgel for the treatment of dermal bacterial infections, as microscopic organisms have created solid resistance against anti-microbials. Methods: Emulgels were prepared and characterized for parameters such as physical examination, rheological studies, spreading coefficient, bio-adhesive strength measurement, extrudability study, antibacterial activity, FTIR analysis, in vitro drug dissolution, and ex vivo permeation studies. Result: With a statistically significant p-value = 0.024, 100% antibacterial activity was observed by F4 against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli (mean ± S.D) (25.33 ± 0.28, 27.33 ± 0.5, and 27 ± 0.5). However, maximum antibacterial effect 100% formulations produced zones of inhibitions against E. colip-value = 0.001. The mean zone of inhibition produced by F4 was greatest among all at 26.44 ± 0.37 mm (mean ± S.D). The F4 formulation produced a maximum percentage dissolution, permeation, and flux of 86.35 ± 0.576, 55.29 ± 0.127%, and 0.5532 ug/cm2/min, respectively. Conclusions: The present study therefore, suggests the use of S. acmella extract and olive oil containing emulgel for treating bacterial skin infections.
Seven Additional Patients with SOX17 Related Pulmonary Arterial Hypertension and Review of the Literature
Authors: Gallego-Zazo Natalia , Miranda-Alcaraz Lucía , Cruz-Utrilla Alejandro , del Cerro Marín María Jesús , Álvarez-Fuente María , del Mar Rodríguez Vázquez del Rey María , Guillén Rodríguez Inmaculada , Becerra-Munoz Victor Manuel , Moya-Bonora Amparo , Ochoa Parra Nuria , Parra Alejandro , Pascual Patricia , Cazalla Mario , Silván Cristina , Arias Pedro , Valverde Diana , de Jesús-Pérez Vinicio , Lapunzina Pablo , Escribano-Subías Pilar , Tenorio-Castano Jair
Published: October 2023

Pulmonary arterial hypertension (PAH) is an infrequent disorder characterized by high blood pressure in the pulmonary arteries. It may lead to premature death or the requirement for lung and/or heart transplantation. Genetics plays an important and increasing role in the diagnosis of PAH. Here, we report seven additional patients with variants in SOX17 and a review of sixty previously described patients in the literature. Patients described in this study suffered with additional conditions including large septal defects, as described by other groups. Collectively, sixty-seven PAH patients have been reported so far with variants in SOX17, including missense and loss-of-function (LoF) variants. The majority of the loss-of-function variants found in SOX17 were detected in the last exon of the gene. Meanwhile, most missense variants were located within exon one, suggesting a probable tolerated change at the amino terminal part of the protein. In addition, we reported two idiopathic PAH patients presenting with the same variant previously detected in five patients by other studies, suggesting a possible hot spot. Research conducted on PAH associated with congenital heart disease (CHD) indicated that variants in SOX17 might be particularly prevalent in this subgroup, as two out of our seven additional patients presented with CHD. Further research is still necessary to clarify the precise association between the biological pathway of SOX17 and the development of PAH.
“The United States of Lyncherdom”: Humor and Outrage in Percival Everett’s The Trees (2021)
Authors: Feith Michel
Published: October 2023

An oeuvre as redolent with the spirit of satire and humor as Percival Everett’s can be said to represent, at the same time, an anthology of humorous devices—a “humorology,” so to speak—and a self-reflexive meditation on the existential, philosophical and/or metaphysical implications of such an attitude to language and life. The Trees (2021) is a book about lynching, in which a series of gruesome murders all allude to the martyrdom of Emmett Till. Even though such subject matter seems antinomic to humor, the novel is rife with it. We propose an examination of the various guises of humor in this text, from wordplay and carnivalesque inversion to the more sinister humour noir, black or gallows humor, and an assessment of their dynamic modus operandi in relation to political satire, literary parody and the expression of the unconscious. The three axes of our analysis of the subversive strategies of the novel will be the poetics of naming, from parody to a form of sublime; the grotesque, macabre treatment of bodies; and the question of affect, the dual tonality of the novel vexingly conjugating the emotional distance and release of humor with a sense of outrage both toned down and exacerbated by ironic indirection. In keeping with the ethos of Menippean satire, humor is, therefore, both medium and message.
The Mediating Effect of Experiential Avoidance on the Relationship between Diabetes Distress and Self-Stigma in People with Diabetes Mellitus Type 2 in Republic of Korea
Authors: Seo Kawoun
Published: October 2023

This descriptive study aimed to explore the mediating role of experiential avoidance in the association between diabetes distress and self-stigma in Korean patients with diabetes mellitus type 2. The study included 196 participants with diabetes mellitus type 2, diagnosed by an endocrinologist. Data were collected from 20 September to 31 September 2021, using an online self-report questionnaire focusing on diabetes distress, diabetes self-stigma, and experiential avoidance. For the mediating effect analysis, a three-step hierarchical multiple analysis was performed using SPSS, and the mediating effect was verified using SPSS PROCESS Macro. The findings revealed that the average scores for diabetes distress, self-stigma, and experiential avoidance were 3.01 ± 0.66, 2.57 ± 0.82, and 3.65 ± 0.55, respectively. Positive correlations were observed among diabetes distress, self-stigma, and experiential avoidance. Specifically, experiential avoidance partially mediated the relationship between diabetes distress and self-stigma, accounting for 47.7% of the variance. These findings reveal that it is crucial to focus on countering experiential avoidance to assist patients with diabetes mellitus type 2 in overcoming the self-stigma and distress related to their condition. In addition, it is necessary to develop a gradual and tailored program aimed at reducing experiential avoidance.
Assistance and Delivery of COVID-19 Vaccinations to Patients with Rare Diseases
Authors: Moraes Mariana Carvalho de , Duarte Ivone , Nunes Rui
Published: October 2023

The COVID-19 vaccination campaign has been fortified by the positive effects of immunization: data from official government organizations and communication channels show that infection rates, hospitalizations, and deaths have continued to fall since its implementation. In Brazil, the effective and free National Vaccination Program has failed to prioritize patients with rare diseases, who have extreme comorbidities, and who adhere to the calendar prepared by the government. The question is why these “rare people” were not considered priorities during the vaccination program. This study aims to understand the reasoning behind this decision and to resume the debate around the rights of patients with rare diseases based on regular descriptors issued by official government agencies and by critics of rare disease issues in scientific articles. The objectives of this study were as follows: to analyze the dispensed care of rare disease patients in the COVID-19 vaccination campaign; to identify the procedures implemented by the National Vaccination Plan for the Brazilian population over 18 years of age and to evaluate the effectiveness of the plan implemented from the perspective of a “rare person”.
A Bibliometric Analysis of the FinTech Agility Literature: Evolution and Review
Authors: Sahid Abdelkebir , Maleh Yassine , Asemanjerdi Shahram Atashi , Martín-Cervantes Pedro Antonio
Published: October 2023

Bibliometric analysis is crucial in understanding the evolution of research trends and knowledge in various fields. This study applies bibliometric analysis to explore the growth of the research paradigm on agility in the FinTech literature, using co-citation analysis and bibliographic coupling of selected articles. Based on this bibliometric analysis, the evolution of research on agility in the FinTech domain has been prepared, focusing on the literature related to FinTech agility between 1984 and 2022. In this study, we also address the limitations of individual analyses from Scopus and Web of Science (WOS) and propose a comprehensive approach by merging the two research databases. The results reveal significant disparities between authors, publication influences, and keyword occurrences between the WOS and merged databases. Our research highlights the importance of combining a database approach in bibliometric studies, providing valuable insights for scholars, researchers, and stakeholders. Finally, the in-depth bibliometric analysis demonstrates the significance of “FinTech agility” in the rapidly evolving FinTech sector. Financial technology companies’ agility, or ability to adapt quickly, is the foundation of their success and innovation.
Thematic Analysis of Big Data in Financial Institutions Using NLP Techniques with a Cloud Computing Perspective: A Systematic Literature Review
Authors: Sharma Ratnesh Kumar , Bharathy Gnana , Karimi Faezeh , Mishra Anil V. , Prasad Mukesh
Published: October 2023

This literature review explores the existing work and practices in applying thematic analysis natural language processing techniques to financial data in cloud environments. This work aims to improve two of the five Vs of the big data system. We used the PRISMA approach (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) for the review. We analyzed the research papers published over the last 10 years about the topic in question using a keyword-based search and bibliometric analysis. The systematic literature review was conducted in multiple phases, and filters were applied to exclude papers based on the title and abstract initially, then based on the methodology/conclusion, and, finally, after reading the full text. The remaining papers were then considered and are discussed here. We found that automated data discovery methods can be augmented by applying an NLP-based thematic analysis on the financial data in cloud environments. This can help identify the correct classification/categorization and measure data quality for a sentiment analysis.
Experimental Study on IRV Ramming Artificial Model Ice
Authors: Guo Chunyu , Zhang Chengsen , Wang Chunhui , Wang Chao
Published: October 2023

When the icebreaker sails in the polar region, it adopts continuous and ramming icebreaking operations. When the ice condition exceeds the design working condition, it uses the ramming icebreaking method to advance. The nonlinear icebreaking process and complex ice conditions make it difficult to accurately predict the ice-strengthened ships’ ramming performance. This paper develops a scale-ratio brittle model of ice to simulate thick, level ice and predicts the ice penetration distance and bow load of an icebreaking research vessel (IRV) model at different speeds. The test results show that the penetration distance of the scoop-shaped bow IRV increases with the ramming speed and the average and extreme values of the contact load increase with the increase in the speed. The experimental results are a valid complement to the ice tank tests and do not cover all aspects of ship design. The main purpose is to develop a test program and performance prediction scheme for studying penetration distance and ice load during ram icebreaking.
Physical Health-Related Quality of Life in Relation to Mediterranean Diet Adherence in a Sample of Greek Asthma Patients: A Pilot Study
Authors: Kontopoulou Lamprini , Kotsiou Ourania S. , Tourlakopoulos Konstantinos , Karpetas Georgios , Paraskevadaki Eva V. , Malli Foteini , Pantazopoulos Ioannis , Daniil Zoe , Gourgoulianis Konstantinos I.
Published: October 2023

The role of nutrition in the management of asthma in obese patients is of increasing interest due to their limited response to inhaled corticosteroids. Some studies note that through diet and lifestyle, there can be an improvement in asthma control. The aim of the present study was to investigate the adherence to the Mediterranean Diet and its association with asthma severity and quality of life in patients with bronchial asthma. This is a cross-sectional study of 85 patients (70.6% female), with a mean age of 57 years, from the General University Hospital of Larissa and, more specifically, patients of the outpatient asthma clinic. Data were collected with the use of specific questionnaires. In relation to BMI, 12.9% of participants were of a normal weight, 45.9% were overweight, 25.9% were obese level I, 5.9% were obese level II, and 9.4% were in the morbidly obese range. Based on the Med Diet Score (ranging from 21 to 35), most participants (85.9%) reported moderate adherence to the Mediterranean Diet. Further analysis examined the correlations of the PCS-12 score with the frequency of consumption of each of the 11 food categories, as well as all demographic and health behavior variables. The ranked correlations indicated a significant relationship between PCS-12 score and Med Diet adherence and the consumption of alcoholic beverages (r = 0.437, p < 0.05), in accordance with the Mediterranean Diet suggestions, as well as a negative relationship with BMI score (r = −0.454, p < 0.010). Moreover, significant correlations were also present between the physical quality of life and AQLQ score and work type, as well as gender, age, and marital status. The results of our study showed a high rate of obesity in patients with asthma at the General University Hospital of Larissa and moderate adherence to the Mediterranean Diet. Increased BMI and alcoholic beverage consumption in asthma patients were significant predictors of lower physical health-related quality of life. In conclusion, personal and society-level interventions are required to effectively address obesity and poor diet in patients with asthma.
Automatic Speech Recognition in L2 Learning: A Review Based on PRISMA Methodology
Authors: Farrús Mireia
Published: October 2023

The language learning field is not exempt from benefiting from the most recent techniques that have revolutionised the field of speech technologies. L2 learning, especially when it comes to learning some of the most spoken languages in the world, is increasingly including more and more automated methods to assess linguistics aspects and provide feedback to learners, especially on pronunciation issues. On the one hand, only a few of these systems integrate automatic speech recognition as a helping tool for pronunciation assessment. On the other hand, most of the computer-assisted language pronunciation tools focus on the segmental level of the language, providing feedback on specific phonetic pronunciation, and disregarding the suprasegmental features based on intonation, among others. The current review, based on the PRISMA methodology for systematic reviews, overviews the existing tools for L2 learning, classifying them in terms of the assessment level, (grammatical, lexical, phonetic, and prosodic), and trying the explain why so few tools are nowadays dedicated to evaluate the intonational aspect. Moreover, the review also addresses the existing commercial systems, as well as the existing gap between those tools and the research developed in this area. Finally, the manuscript finishes with a discussion of the main findings and foresees future lines of research.
Evidential Adverbs and Polarity: A Study from Spanish
Authors: Rodríguez Ramalle Teresa María
Published: October 2023

This paper addresses the analysis of variations in structures that are projected in discourse. Starting with the relationship between evidential adverbs and the affirmative Spanish adverb sí, I review the occurrence of the conjunction que “that” with evidential adverbs, such as naturalmente “naturally”, ciertamente “certainly”, obviamente “obviously”, and evidentemente “evidently” as a Hispanic phenomenon, as well as its value and development in different varieties of Spanish. Although it appears that Latin American Spanish varieties lack an overt que in certain situations, such as sí que contexts or recomplementation, studies of the construction with evidential adverbs in language varieties different from European Spanish remain limited. I use examples extracted from CREA and CORPES XXI. My main objectives are to review the presence of the construction with evidential adverb + que (“that”) in Spanish by paying particular attention to its distribution in Latin American countries and to study the basic uses of the construction in countries in which it is documented.
Community Structure and Resilience of the City Logistics Networks in China
Authors: Ma Jun-Chao , Jiang Zhi-Qiang , Ma Yin-Jie , Dai Yue-Hua
Published: October 2023

Logistics security, as the lifeline of the economy connecting production, distribution, and consumption, holds a pivotal position in the modern economic system, where any potential threats like natural disasters or cyber attacks could have far-reaching impacts on the overall economy. With a unique large-scale logistics data set, logistics networks between cities in China are constructed. We thus identify communities of cities that have dense logistics connections in these networks. The cities in the communities are found to exhibit strong connections in the economy, resources, and industry. The detected communities are also aligned with the urban agglomerations mentioned in the guidelines reported by the National Development and Reform Commission of China. We further extend our analysis to assess the resilience of the city logistics networks, especially focusing on the influence of community structures. Random and intentional attacks are considered in our resilience analysis. Our results reveal that the city logistics networks are robust to the random attacks and are vulnerable to the intentional attacks on the nodes with dense links between and within communities. Our results not only deepen our understanding of the community structure and resilience of the city logistics networks but also provide insights on how to improve the efficiency and safety of intercity logistics.
VaR Estimation with Quantum Computing Noise Correction Using Neural Networks
Authors: de Pedro Luis , París Murillo Raúl , López de Vergara Jorge E. , López-Buedo Sergio , Gómez-Arribas Francisco J.
Published: October 2023

In this paper, we present the development of a quantum computing method for calculating the value at risk (VaR) for a portfolio of assets managed by a finance institution. We extend the conventional Monte Carlo algorithm to calculate the VaR of an arbitrary number of assets by employing random variable algebra and Taylor series approximation. The resulting algorithm is suitable to be executed in real quantum computers. However, the noise affecting current quantum computers renders them almost useless for the task. We present a methodology to mitigate the noise impact by using neural networks to compensate for the noise effects. The system combines the output from a real quantum computer with the neural network processing. The feedback is used to fine tune the quantum circuits. The results show that this approach is useful for estimating the VaR in finance institutions, particularly when dealing with a large number of assets. We demonstrate the validity of the proposed method with up to 139 assets. The accuracy of the method is also proven. We achieved an error of less than 1% in the empirical measurements with respect to the parametric model.
Local Sensitivity of Failure Probability through Polynomial Regression and Importance Sampling
Authors: Chiron Marie , Morio Jérôme , Dubreuil Sylvain
Published: October 2023

Evaluating the failure probability of a system is essential in order to assess its reliability. This probability may significantly depend on deterministic parameters such as distribution parameters or design parameters. The sensitivity of the failure probability with regard to these parameters is then critical for the reliability analysis of the system or in reliability-based design optimization. Here, we introduce a new approach to estimate the failure probability derivatives with respect to deterministic inputs, where the bias can be controlled and the simulation budget is kept low. The sensitivity estimate is obtained as a byproduct of a heteroscedastic polynomial regression with a database built with simulation methods. The polynomial comes from a Taylor series expansion of the approximated sensitivity domain integral obtained with the Weak approach. This new methodology is applied to two engineering use cases with the importance sampling strategy.
A Population-Based Local Search Algorithm for the Identifying Code Problem
Authors: Lara-Caballero Alejandro , González-Moreno Diego
Published: October 2023

The identifying code problem for a given graph involves finding a minimum subset of vertices such that each vertex of the graph is uniquely specified by its nonempty neighborhood within the identifying code. The combinatorial optimization problem has a wide variety of applications in location and detection schemes. Finding an identifying code of minimum possible size is a difficult task. In fact, it has been proven to be computationally intractable (NP-complete). Therefore, the use of heuristics to provide good approximations in a reasonable amount of time is justified. In this work, we present a new population-based local search algorithm for finding identifying codes of minimum cost. Computational experiments show that the proposed approach was found to be more effective than other state-of-the-art algorithms at generating high-quality solutions in different types of graphs with varying numbers of vertices.
Enhancing Pneumonia Segmentation in Lung Radiographs: A Jellyfish Search Optimizer Approach
Authors: Zarate Omar , Zaldívar Daniel , Cuevas Erik , Perez Marco
Published: October 2023

Segmentation of pneumonia on lung radiographs is vital for the precise diagnosis and monitoring of the disease. It enables healthcare professionals to locate and quantify the extent of infection, guide treatment decisions, and improve patient care. One of the most-employed approaches to effectively segment pneumonia in lung radiographs is to treat it as an optimization task. By formulating the problem in this manner, it is possible to use the interesting capabilities of metaheuristic methods to determine the optimal segmentation solution. Although these methods produce interesting results, they frequently produce suboptimal solutions owing to the lack of exploration of the search space. In this paper, a new segmentation method for segmenting pneumonia in lung radiographs is introduced. The algorithm is based on the jellyfish search optimizer (JSO), which is characterized by its excellent global exploration capability and robustness. This method uses an energy curve based on cross-entropy as a cost function that penalizes misclassified pixels more heavily, leading to a sharper focus on regions where segmentation errors occur. This is particularly important because it allows for the accurate delineation of objects or regions of interest. To validate our proposed approach, we conducted extensive testing on the most widely available datasets. The results of our method were compared with those obtained using other established techniques. The results of our evaluation demonstrate that our approach consistently outperforms the other methods at levels 8, 16, and 32, with a difference of more than 10%.
An Adaptive Mixup Hard Negative Sampling for Zero-Shot Entity Linking
Authors: Cai Shisen , Wu Xi , Maimaiti Maihemuti , Chen Yichang , Wang Zhixiang , Zheng Jiong
Published: October 2023

Recently, the focus of entity linking research has centered on the zero-shot scenario, where the entity purposed to be labeled at the time of testing was never observed during the training phase, or it may belong to a different domain than the source domain. Current studies have used BERT as the base encoder, as it effectively establishes distributional links between source and target domains. The currently available negative sampling methods all use an extractive approach, which makes it difficult for the models to learn diverse and more challenging negative samples. To address this problem, we propose a generative negative sampling method, adaptive_mixup_hard, which generates more difficult negative entities by fusing the features of both positive and negative samples on top of hard negative sampling and introduces a transformable adaptive parameter, W, to increase the diversity of negative samples. Next, we fuse our method with the Biencoder architecture and evaluate its performance under three different score functions. Ultimately, experimental results on the standard benchmark dataset, Zeshel, demonstrate the effectiveness of our method.
Some Classes of Soft Functions Defined by Soft Open Sets Modulo Soft Sets of the First Category
Authors: Ameen Zanyar A. , Alqahtani Mesfer H.
Published: October 2023

Soft continuity can contribute to the development of digital images and computational topological applications other than the field of soft topology. In this work, we study a new class of generalized soft continuous functions defined on the class of soft open sets modulo soft sets of the first category, which is called soft functions with the Baire property. This class includes all soft continuous functions. More precisely, it contains various classes of weak soft continuous functions. The essential properties and operations of the soft functions with the Baire property are established. It is shown that a soft continuous with values in a soft second countable space is identical to a soft function with the Baire property, apart from a topologically negligible soft set. Then we introduce two more subclasses of soft functions with the Baire property and examine their basic properties. Furthermore, we characterize these subclasses in terms of soft continuous functions. At last, we present a diagram that shows the relationships between the classes of soft functions defined in this work and those that exist in the literature.
Microstructural Transformations in Solid-State Annealed Al/Ag/Al Diffusion Couples Examined via High-Voltage Electron Microscopy (HVEM)
Authors: Oh Minho , Kajihara Masanori
Published: October 2023

This study focuses on the practical relevance of the Al-Ag bonding interface in electronic device fabrication, particularly in wire bonding, which is crucial for enhancing component reliability and performance. Experiments involved Al/Ag/Al diffusion couples, annealed at 703 K, revealing two stable intermediate phases, μ and δ. Characterizing the intermediate phases’ compositions and concentration profiles exposed a vital transition at the δ-Al interface. We used high-voltage electron microscopy (HVEM) to examine crystal structure evolution, identifying a (hexagonal close-packed) hcp structure in the intermediate phase between δ and Al, matching the δ phase. Notably, a substantial microstructural transformation occurred within the Ag-Al diffusion couple, as nano-sized precipitates transitioned from spherical to plate-like, along specific {111} planes, reflecting the evolution from off-stoichiometric, disordered phases to ordered ones. Mapping the concentrations of intermediate phases on the Al-Ag phase diagram revealed shifted and narrower solubility ranges compared to the calculations. This study provides insight into the crystal structure and microstructure changes during diffusion in Al/Ag/Al diffusion couples, holding implications for electronic device fabrication. Understanding intermediate phase behavior and evolution is vital in this context, potentially influencing materials development and process optimization in the electronic components industry, and thus, enhancing device performance and reliability.
Hot Work Mold Repaired via Hot Isostatic Pressing towards High Red Hardness
Authors: Ge Xueyuan , Ma Qingxian , Chen Yunbo , Wang Miaohui , Hu Qipeng
Published: October 2023

Repairing hot work molds can extend their lifespans and reduce the production costs. This study presents a proposed method for enhancing the red hardness and strength of repaired molds. The method involves utilizing PM23 high-speed steel powder to repair H13 steel molds with two distinct surface states through the process of hot isostatic pressing (HIP). The internal microstructure changes, bonding state, fracture morphology, and crack extension behaviors of the repaired molds are characterized using scanning electron microscopy and electron backscatter diffraction technology. Additionally, the mechanical properties, including red hardness and tensile strength, are quantitatively analyzed. The findings indicate that the repaired area in the sandblasted sample exhibits a rough and uneven structure, demonstrating exceptional toughness. The tensile strength of the repaired region is approximately 1195.42 MPa, while the hardness measures around 672.8 HV. These properties effectively enhance the performance of the molds. The experimental findings indicate that HIP can effectively restore molds, resulting in enhanced red hardness and improved toughness, particularly when combined with sandblasting as a pretreatment method.
Uncovering the Interrelation between Metabolite Profiles and Bioactivity of In Vitro- and Wild-Grown Catmint (Nepeta nuda L.)
Authors: Zaharieva Anna , Rusanov Krasimir , Rusanova Mila , Paunov Momchil , Yordanova Zhenya , Mantovska Desislava , Tsacheva Ivanka , Petrova Detelina , Mishev Kiril , Dobrev Petre I. , Lacek Jozef , Filepová Roberta , Zehirov Grigor , Vassileva Valya , Mišić Danijela , Motyka Václav , Chaneva Ganka , Zhiponova Miroslava
Published: October 2023

Nepeta nuda L. is a medicinal plant enriched with secondary metabolites serving to attract pollinators and deter herbivores. Phenolics and iridoids of N. nuda have been extensively investigated because of their beneficial impacts on human health. This study explores the chemical profiles of in vitro shoots and wild-grown N. nuda plants (flowers and leaves) through metabolomic analysis utilizing gas chromatography and mass spectrometry (GC–MS). Initially, we examined the differences in the volatiles’ composition in in vitro-cultivated shoots comparing them with flowers and leaves from plants growing in natural environment. The characteristic iridoid 4a-α,7-β,7a-α-nepetalactone was highly represented in shoots of in vitro plants and in flowers of plants from nature populations, whereas most of the monoterpenes were abundant in leaves of wild-grown plants. The known in vitro biological activities encompassing antioxidant, antiviral, antibacterial potentials alongside the newly assessed anti-inflammatory effects exhibited consistent associations with the total content of phenolics, reducing sugars, and the identified metabolic profiles in polar (organic acids, amino acids, alcohols, sugars, phenolics) and non-polar (fatty acids, alkanes, sterols) fractions. Phytohormonal levels were also quantified to infer the regulatory pathways governing phytochemical production. The overall dataset highlighted compounds with the potential to contribute to N. nuda bioactivity.
Investigating the Influence of Probe Pressure on Human Skin Using Diffusive Reflection Spectroscopy
Authors: Ahmed Israr , Ali Murad , Butt Haider
Published: October 2023

The skin has emerge as a compelling subject for investigation owing to its accessibility and the relatively straightforward application of optical procedures to it. Diffusive reflection spectroscopy (DRS) was employed to study the influence of probe pressure on human skin. A comprehensive non-invasive study was conducted, which covers almost all the important body parts for in vivo measurements. Reflection spectra were measured for the fingertip, forearm, forehead, neck, and foot under a set of probe pressures (0–265 kPa). Importantly, each tissue type’s unique composition and morphology influenced the shape, size, intensity, and position of the recorded peak, highlighting the tissue-specific responses to pressure. In addition, time-based reflection spectroscopy was also performed on the forearm under blood occlusion for 5 min to study the effect. DRS measurements were performed on volunteers of different skin tones, including dark, medium, and fair. Later, a change in the intensity of the oxyhemoglobin peak was confirmed using a green laser light of a wavelength of 532 nm. Besides the dermal studies, diffusive reflection spectroscopy was also employed to investigate the probe pressure effect on human nails. A probe pressure ranging from 0 to 385 kPa was applied for nail spectroscopy. The same trend of intensity change was observed following the previous measurements. The suggested sensing system may be crucial in applications requiring pressure sensing when the human body is subjected to varying pressures, such as exercise, weightlifting, and other sports.
Loss of Biliverdin Reductase Increases Oxidative Stress in the Cyanobacterium Synechococcus sp. PCC 7002
Authors: Schluchter Wendy M. , Babin Courtney H. , Liu Xindi , Bieller Amori , Shen Gaozhong , Alvey Richard M. , Bryant Donald A.
Published: October 2023

Oxygenic photosynthesis requires metal-rich cofactors and electron-transfer components that can produce reactive oxygen species (ROS) that are highly toxic to cyanobacterial cells. Biliverdin reductase (BvdR) reduces biliverdin IXα to bilirubin, which is a potent scavenger of radicals and ROS. The enzyme is widespread in mammals but is also found in many cyanobacteria. We show that a previously described bvdR mutant of Synechocystis sp. PCC 6803 contained a secondary deletion mutation in the cpcB gene. The bvdR gene from Synechococcus sp. PCC 7002 was expressed in Escherichia coli, and recombinant BvdR was purified and shown to reduce biliverdin to bilirubin. The bvdR gene was successfully inactivated in Synechococcus sp. PCC 7002, a strain that is naturally much more tolerant of high light and ROS than Synechocystis sp. PCC 6803. The bvdR mutant strain, BR2, had lower total phycobiliprotein and chlorophyll levels than wild-type cells. As determined using whole-cell fluorescence at 77 K, the photosystem I levels were also lower than those in wild-type cells. The BR2 mutant had significantly higher ROS levels compared to wild-type cells after exposure to high light for 30 min. Together, these results suggest that bilirubin plays an important role as a scavenger for ROS in Synechococcus sp. PCC 7002. The oxidation of bilirubin by ROS could convert bilirubin to biliverdin IXα, and thus BvdR might be important for regenerating bilirubin. These results further suggest that BvdR is a key component of a scavenging cycle by which cyanobacteria protect themselves from the toxic ROS byproducts generated during oxygenic photosynthesis.
Alteration in Community Dynamics of Chaetoceros curvisetus and Bacterioplankton Communities in Response to Surfactin Exposure
Authors: Shao Qianwen , Zhu Zhujun , Zhou Chengxu
Published: October 2023

The use of surfactin is a promising method to mitigate algal blooms. However, little is known about surfactin toxicity to algae and bacterioplankton. Here, we treated Chaetoceros curvisetus, the dominant species of algal blooms in the East China Sea, with 0, 0.5, 1, 2, 3, and 4 mg/L of surfactin for 96 h to investigate temporal variability. Our results showed that low concentrations of surfactin (<2 mg/L) changed the cell morphology of C. curvisetus, and higher concentrations (>3 mg/L) had lethal effects. Meanwhile, we examined the community dynamics of the free-living (FL, 0.22–5 μm) and particle-attached (PA, >5 μm) bacterioplankton of C. curvisetus in response to different surfactin concentrations and cultivation periods. Both PA and FL bacterioplankton were mainly composed of Proteobacteria, Actinobacteria, and Bacteroidetes, while FL bacterioplankton were more diverse than PA bacterioplankton. The variations of FL and PA bacterioplankton were significantly constrained by the surfactin concentration. Surfactin changed the lifestyle of some bacterioplankton from FL to PA, which mainly belonged to abundant bacterioplankton. Furthermore, we identified some surfactin-sensitive species/taxa. Our study will help enhance the ability to predict marine microbial responses under the effect of surfactin, providing a research foundation for this new harmful algal bloom mitigation method.
Anti-Malassezia Drug Candidates Based on Virulence Factors of Malassezia-Associated Diseases
Authors: Billamboz Muriel , Jawhara Samir
Published: October 2023

Malassezia is a lipophilic unicellular fungus that is able, under specific conditions, to cause severe cutaneous and systemic diseases in predisposed subjects. This review is divided into two complementary parts. The first one discusses how virulence factors contribute to Malassezia pathogenesis that triggers skin diseases. These virulence factors include Malassezia cell wall resistance, lipases, phospholipases, acid sphingomyelinases, melanin, reactive oxygen species (ROS), indoles, hyphae formation, hydrophobicity, and biofilm formation. The second section describes active compounds directed specifically against identified virulence factors. Among the strategies for controlling Malassezia spread, this review discusses the development of aryl hydrocarbon receptor (AhR) antagonists, inhibition of secreted lipase, and fighting biofilms. Overall, this review offers an updated compilation of Malassezia species, including their virulence factors, potential therapeutic targets, and strategies for controlling their spread. It also provides an update on the most active compounds used to control Malassezia species.
pH-Sensitive Nanoparticles for Colonic Delivery Anti-miR-301a in Mouse Models of Inflammatory Bowel Diseases
Authors: Wang Junshan , Yao Min , Zou Jiafeng , Ding Wenxing , Sun Mingyue , Zhuge Ying , Gao Feng
Published: October 2023

Though the anti-miR-301a (anti-miR) is a promising treatment strategy for inflammatory bowel disease (IBD), the degradability and the poor targeting of the intestine are a familiar issue. This study aimed to develop a multifunctional oral nanoparticle delivery system loaded with anti-miR for improving the targeting ability and the therapeutic efficacy. The HA-CS/ES100/PLGA nanoparticles (HCeP NPs) were prepared using poly (lactic-co-glycolic acid) copolymer (PLGA), enteric material Eudragit®S100 (ES100), chitosan (CS), and hyaluronic acid (HA). The toxicity of nanoparticles was investigated via the Cell Counting Kit-8, and the cellular uptake and inflammatory factors of nanoparticles were further studied. Moreover, we documented the colon targeting and pharmacodynamic properties of nanoparticles. The nanoparticles with uniform particle size exhibited pH-sensitive release, favorable gene protection, and storage stability. Cytology experiments showed that anti-miR@HCeP NPs improved the cellular uptake through HA and reduced pro-inflammatory factors. Administering anti-miR@HCeP NPs orally to IBD mice markedly reduced their pro-inflammatory factors levels and disease activity indices. We also confirmed that anti-miR@HCeP NPs mostly accumulated in the colon site, and effectively repaired the intestinal barrier, as well as relieved intestinal inflammation. The above nanoparticle is a candidate of the treatment for IBD due to its anti-inflammatory properties.
Freeze-Dried Camelina Lipid Droplets Loaded with Human Basic Fibroblast Growth Factor-2 Formulation for Transdermal Delivery: Breaking through the Cuticle Barrier to Accelerate Deep Second-Degree Burn Healing
Authors: Gao Hongtao , Wang Xue , Wu Hao , Zhang Yuan , Zhang Wenxiao , Wang Zuobin , Liu Xin , Li Xiaokun , Li Haiyan
Published: October 2023

Transdermal administration of chemo therapeutics into burn healing may be an effective treatment to reduce toxic side effects and improve patient compliance for burns. As a transdermal delivery system, Camelina lipid droplets (CLDs) have received great attention due to their biocompatibility, high drug payload, and rapid absorption. However, the absorbed-related mechanisms of Camelina lipid droplets have not yet been reported. Thus, this paper not only demonstrated that CLD can accelerate skin burn healing through promoting hFGF2 absorption, but also elucidated the mechanism between the skin tissue and keratinocytes using Franz, HE staining, DSC, FTIR spectroscopy, and atomic force microscopy with the presence of CLD-hFGF2 freeze-dried powder. We found that the cumulative release rate of CLD-hFGF2 freeze-dried powder was significantly higher than that of free hFGF2 freeze-dried powder into the skin. At the same time, CLD can change the structure and content of lipids and keratin to increase the permeability of hFGF2 freeze-dried powder in skin tissue. Unlike the free state of hFGF2, the biophysical properties of single cells, including height and adhesion force, were changed under CLD-hFGF2 freeze-dried powder treatment. Meanwhile, CLD-hFGF2 freeze-dried powder was more easily taken up through keratinocytes without damaging cell integrity, which provided a new viewpoint for understanding the absorption mechanism with the CLD system for cellular physiology characteristics. Overall, our findings demonstrated that CLD could break through the stratum corneum (SC) barrier and elucidated the transport mechanism of lipid droplets in skin tissue, which provides a crucial guideline in drug delivery applications for future engineering.
Predictive Potential of Cmax Bioequivalence in Pilot Bioavailability/Bioequivalence Studies, through the Alternative ƒ2 Similarity Factor Method
Authors: Henriques Sara Carolina , Paixão Paulo , Almeida Luis , Silva Nuno Elvas
Published: October 2023

Pilot bioavailability/bioequivalence (BA/BE) studies are downsized trials that can be conducted prior to the definitive pivotal trial. In these trials, 12 to 18 subjects are usually enrolled, although, in principle, a sample size is not formally calculated. In a previous work, authors recommended the use of an alternative approach to the average bioequivalence methodology to evaluate pilot studies’ data, using the geometric mean (Gmean) ƒ2 factor with a cut off of 35, which has shown to be an appropriate method to assess the potential bioequivalence for the maximum observed concentration (Cmax) metric under the assumptions of a true Test-to-Reference Geometric Mean Ratio (GMR) of 100% and an inter-occasion variability (IOV) in the range of 10% to 45%. In this work, the authors evaluated the proposed ƒ2 factor in comparison with the standard average bioequivalence in more extreme scenarios, using a true GMR of 90% or 111% for truly bioequivalent formulations, and 80% or 125% for truly bioinequivalent formulations, in order to better derive conclusions on the potential of this analysis method. Several scenarios of pilot BA/BE crossover studies were simulated through population pharmacokinetic modelling, accounting for different IOV levels. A redefined decision tree is proposed, suggesting a fixed sample size of 20 subjects for pilot studies in the case of intra-subject coefficient of variation (ISCV%) > 20% or unknown variability, and suggesting the assessment of study results through the average bioequivalence analysis, and additionally through Gmean ƒ2 factor method in the case of the 90% confidence interval (CI) for GMR is outside the regulatory acceptance bioequivalence interval of [80.00–125.00]%. Using this alternative approach, the certainty levels to proceed with pivotal studies, depending on Gmean ƒ2 values and variability scenarios tested (20–60% IOV), were assessed, which is expected to be helpful in terms of the decision to proceed with pivotal bioequivalence studies.
Contribution to the Synthesis, Characterization, Separation and Quantification of New N-Acyl Thiourea Derivatives with Antimicrobial and Antioxidant Potential
Authors: Roman Roxana , Pintilie Lucia , Nuță Diana Camelia , Căproiu Miron Teodor , Dumitrașcu Florea , Zarafu Irina , Ioniță Petre , Marinaș Ioana Cristina , Măruțescu Luminița , Kapronczai Eleonora , Ardelean Simona , Limban Carmen
Published: October 2023

The present study aimed to synthesize, characterize, and validate a separation and quantification method of new N-acyl thiourea derivatives (1a–1o), incorporating thiazole or pyridine nucleus in the same molecule and showing antimicrobial potential previously predicted in silico. The compounds have been physiochemically characterized by their melting points, IR, NMR and MS spectra. Among the tested compounds, 1a, 1g, 1h, and 1o were the most active against planktonic Staphylococcus aureus and Pseudomonas aeruginosa, as revealed by the minimal inhibitory concentration values, while 1e exhibited the best anti-biofilm activity against Escherichia coli (showing the lowest value of minimal inhibitory concentration of biofilm development). The total antioxidant activity (TAC) assessed by the DPPH method, evidenced the highest values for the compound 1i, followed by 1a. A routine quality control method for the separation of highly related compounds bearing a chlorine atom on the molecular backbone (1g, 1h, 1i, 1j, 1m, 1n) has been developed and validated by reversed-phase high-performance liquid chromatography (RP—HPLC), the results being satisfactory for all validation parameters recommended by the ICH guidelines (i.e., system suitability, specificity, the limits of detection and quantification, linearity, precision, accuracy and robustness) and recommending it for routine separation of these highly similar compounds.