bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimum-Effort Waypoint-Following Differential Geometric Guidance Law Design for Endo-Atmospheric Flight Vehicles
Authors: Qin Xuesheng , Li Kebo , Liang Yangang , Liu Yuanhe
Published: June 2023

To improve the autonomous flight capability of endo-atmospheric flight vehicles, such as cruise missiles, drones, and other small, low-cost unmanned aerial vehicles (UAVs), a novel minimum-effort waypoint-following differential geometric guidance law (MEWFDGGL) is proposed in this paper. Using the classical differential geometry curve theory, the optimal guidance problem of endo-atmospheric flight vehicles is transformed into an optimal space curve design problem, where the guidance command is the curvature. On the one hand, the change in speed of the flight vehicle is decoupled from the guidance problem. In this way, the widely adopted constant speed hypothesis in the process of designing the guidance law is eliminated, and, hence, the performance of the proposed MEWFDGGL is not influenced by the varying speed of the flight vehicle. On the other hand, considering the onboard computational burden, a suboptimal form of the MEWFDGGL is proposed to solve the problem, where both the complexity and the computational burden of the guidance law dramatically increase as the number of waypoints increases. The theoretical analysis demonstrates that both the original MEWFDGGL and its suboptimal form can be applied to general waypoint-following tasks with an arbitrary number of waypoints. Finally, the superiority and effectiveness of the proposed MEWFDGGL are verified by a numerical simulation and flight experiments.
Hydrogen or Electric Drive—Inconvenient (Omitted) Aspects
Authors: Konieczny Jarosław , Labisz Krzysztof , Surma Szymon , Młyńczak Jakub , Łukasik Jerzy , Boris Renata , Grzybowski Michał
Published: May 2023

Currently, hydrogen and electric drives used in various means of transport is a leading topic in many respects. This article discusses the most important aspects of the operation of vehicles with electric drives (passenger cars) and hydrogen drives. In both cases, the official reason for using both drives is the possibility of independence from fossil fuel supplies, especially oil. The desire for independence is mainly dictated by political considerations. This article discusses the acquisition of basic raw materials for the construction of lithium-ion batteries in electric cars, as well as methods for obtaining hydrogen as a fuel. The widespread use of electric passenger cars requires the construction of a network of charging stations. This article shows that, taking into account the entire production process of electric cars, including lithium-ion batteries, the argument that they are ecological cannot be used. Additionally, it was indicated that there is no concept for the use of used accumulator batteries. If hydrogen drives are used in trains, there is no need to build the traction network infrastructure and then continuously monitor its technical condition and perform the necessary repairs. Of course, the necessary hydrogen tanks must be built, but there must be similar tanks to store oil for diesel locomotives. This paper also deals with other possibilities of hydrogen application for transformational usage, e.g., the use of combustion engines driven with liquid hydrogen. Unfortunately, an optimistic approach to this issue does not allow for a critical view of the whole matter. In public discussion, there is no room for scientific arguments and emotions to dominate.
Analytical Model of Interaction of an Oil Pipeline with a Support of an Overpass Built in a Mountainous Area
Authors: Dutkiewicz Maciej , Velychkovych Andrii , Andrusyak Andriy , Petryk Ivan , Kychma Andrii
Published: June 2023

Today, pipelines are the safest and most economical way to transport petroleum products and one of the key components of modern energy infrastructure. Nevertheless, pipeline systems are associated with certain risks that can lead to environmental disasters. The idea of carrying out this study was initiated by the results of the survey of the overpasses of the long-used oil pipelines laid in the mountainous area of the Carpathian region. Defects such as a change in the shape of the pipe and local bulges in the area of oil pipeline support nodes were detected. The explanation of the described problem is separate from the typical algorithms of design calculations, which are offered to manufacturers by current directive documents. The desire to provide an explanation and quantitative assessment of the detected defects became the main motivation for writing the article. An analytical model of the interaction of the oil pipeline with the rigid support has been developed. Additional internal loads in the cross-section of the pipe and displacement of its middle surface, which arise as a result of such interaction, are determined. The method of determining the reaction in the intermediate support of the overpass of the oil pipeline has been developed, considering the properties of the soil base in the underground sections and the mounting gap in the support node. The analytical dependence was obtained to determine the additional hoop stresses that arise in the oil pipeline due to the contact of the pipe with the support. The unambiguous relationship between the maximum additional hoop stress and the reaction in the support node was established. The dependence of additional hoop stresses on the geometric characteristics of the pipes was analyzed. The obtained research results are tested on the real structure of the overpass of the Druzhba oil pipeline, built in the Carpathians. In general, a simple engineering technique has been developed that allows analyzing the behavior of the oil pipeline support node and provides the numerical correction to the traditional strength assessment formulas, which determine the equivalent stresses in the oil pipeline.
Study Models of COVID-19 in Discrete-Time and Fractional-Order
Authors: Djeddi Kamel , Bouali Tahar , Msmali Ahmed H. , Ahmadini Abdullah Ali H. , Koam Ali N. A.
Published: June 2023

The novel coronavirus disease (SARS-CoV-2) has caused many infections and deaths throughout the world; the spread of the coronavirus pandemic is still ongoing and continues to affect healthcare systems and economies of countries worldwide. Mathematical models are used in many applications for infectious diseases, including forecasting outbreaks and designing containment strategies. In this paper, we study two types of SIR and SEIR models for the coronavirus. This study focuses on the discrete-time and fractional-order of these models; we study the stability of the fixed points and orbits using the Jacobian matrix and the eigenvalues and eigenvectors of each case; moreover, we estimate the parameters of the two systems in fractional order. We present a statistical study of the coronavirus model in two countries: Saudi Arabia, which has successfully recovered from the SARS-CoV-2 pandemic, and China, where the number of infections remains significantly high.
Solvability for the ψ-Caputo-Type Fractional Differential System with the Generalized p-Laplacian Operator
Authors: Li Yankai , Li Dongping , Jiang Yi , Feng Xiaozhou
Published: June 2023

In this article, by combining a recent critical point theorem and several theories of the ψ-Caputo fractional operator, the multiplicity results of at least three distinct weak solutions are obtained for a new ψ-Caputo-type fractional differential system including the generalized p-Laplacian operator. It is noted that the nonlinear functions do not need to adapt certain asymptotic conditions in the paper, but, instead, are replaced by some simple algebraic conditions. Moreover, an evaluation criterion of the equation without solutions is also provided. Finally, two examples are given to demonstrate that the ψ-Caputo fractional operator is more accurate and can adapt to deal with complex system modeling problems by changing different weight functions.
Prediction of In-Hospital Falls Using NRS, PACD Score and FallRS: A Retrospective Cohort Study
Authors: Siegwart Jennifer , Spennato Umberto , Lerjen Nathalie , Mueller Beat , Schuetz Philipp , Koch Daniel , Struja Tristan
Published: June 2023

Background: Harmful in-hospital falls with subsequent injuries often cause longer stays and subsequently higher costs. Early identification of fall risk may help in establishing preventive strategies. Objective: To assess the predictive ability of different clinical scores including the Post-acute care discharge (PACD) score and nutritional risk screening score (NRS), and to develop a new fall risk score (FallRS). Methods: A retrospective cohort study of medical in-patients of a Swiss tertiary care hospital from January 2016 to March 2022. We tested the ability of the PACD score, NRS and FallRS to predict a fall by using the area under curve (AUC). Adult patients with a length of stay of ≥ 2 days were eligible. Results: We included 19,270 admissions (43% females; median age, 71) of which 528 admissions (2.74%) had at least one fall during the hospital stay. The AUC varied between 0.61 (95% confidence interval (CI), 0.55–0.66) for the NRS and 0.69 (95% CI, 0.64–0.75) for the PACD score. The combined FallRS score had a slightly better AUC of 0.70 (95% CI, 0.65–0.75) but was more laborious to compute than the two other scores. At a cutoff of 13 points, the FallRS had a specificity of 77% and a sensitivity of 49% in predicting falls. Conclusions: We found that the scores focusing on different aspects of clinical care predicted the risk of falls with fair accuracy. A reliable score with which to predict falls could help in establishing preventive strategies for reducing in-hospital falls. Whether or not the scores presented have better predictive ability than more specific fall scores do will need to be validated in a prospective study.
Differences in Physical Activity Patterns among Korean Adolescents during and after COVID-19
Authors: Yun Juseok , Lee Seungman
Published: June 2023

Due to the COVID-19-induced social distancing restrictions, adolescents’ physical activity declined and their level of health and fitness decreased. In March 2023, the Korean government established the beginning of the post-COVID-19 era by declaring that indoor masks were now “recommended” rather than “mandatory”. Consequently, adolescents, whose physical activity decreased during COVID-19, began to participate in such activities again. This study aimed to verify the differences in adolescent physical activity during COVID-19 and after COVID-19. To achieve the study’s purpose, an online survey was conducted twice, using the International Physical Activity Questionnaire, for 1143 Korean adolescents in 2022 and 2023. The following results were derived through frequency analysis, descriptive statistical analysis, and an independent variables t-test. First, moderate-to-vigorous physical activity was higher during the post-COVID-19 period than during COVID-19 (p = 0.018). Second, high-intensity (p = 0.018), moderate-intensity (p = 0.030), and low-intensity (p = 0.002) physical activities and total leisure-time physical activities (p = 0.003) were all higher during the post-COVID-19 period than during COVID-19. Third, high-intensity (p = 0.005), moderate-intensity (p = 0.003), low-intensity (p = 0.003) activities and total physical activities in school (p = 0.001) were all higher during the post-COVID-19 period than during COVID-19. Fourth, there was no difference in the commuting times for cycling (p = 0.515) and walking (p = 0.484) and the total physical activities during commuting (p = 0.375) during and after COVID-19. Based on these results, the methods to help adolescents form correct habits for leading a healthy life are discussed.
Exploring Older Adults’ Willingness to Install Home Surveil-Lance Systems in Taiwan: Factors and Privacy Concerns
Authors: Wang Chang-Yueh , Lin Fang-Suey
Published: June 2023

Taiwan has a rapidly increasing aging population with a considerably high life expectancy rate, which poses challenges for healthcare and medical systems. This study examines three key factors: safety concerns, family expectations, and privacy concerns, and their influence on surveillance system installation decisions. A cross-sectional study was conducted involving a group of physically active older adults in Taiwan, using a questionnaire to collect data on the reasons for in-stalling a surveillance system and preferences for three image privacy protection techniques: blurring the face and transformation to a 2D or 3D character. The study concluded that while safety concerns and family expectations facilitate the adoption of surveillance systems, privacy concerns serve as a significant barrier. Furthermore, older adults showed a clear preference for avatar-based privacy protection methods over simpler techniques, such as blurring. The outcomes of this research will be instrumental in shaping the development of privacy-conscious home surveillance technologies, adeptly balancing safety and privacy. This understanding can pave the way for technology design that skillfully balances privacy concerns with remote monitoring quality, thereby enhancing the well-being and safety of this demographic. These results could possibly be extended to other demographics as well.
State-of-the-Art Molecular Oncology in Brazil
Authors: Rodrigues Tiago
Published: May 2023

Over the past few decades, the life expectancy of humankind has increased significantly due to advancements in life sciences and medical research, particularly given our increasing success in the epidemiological and pharmacological management of bacterial, fungi, and viral infections [...]
Deciphering the Cardiovascular Potential of Human CD34+ Stem Cells
Authors: Aries Anne , Zanetti Céline , Hénon Philippe , Drénou Bernard , Lahlil Rachid
Published: June 2023

Ex vivo monitored human CD34+ stem cells (SCs) injected into myocardium scar tissue have shown real benefits for the recovery of patients with myocardial infarctions. They have been used previously in clinical trials with hopeful results and are expected to be promising for cardiac regenerative medicine following severe acute myocardial infarctions. However, some debates on their potential efficacy in cardiac regenerative therapies remain to be clarified. To elucidate the levels of CD34+ SC implication and contribution in cardiac regeneration, better identification of the main regulators, pathways, and genes involved in their potential cardiovascular differentiation and paracrine secretion needs to be determined. We first developed a protocol thought to commit human CD34+ SCs purified from cord blood toward an early cardiovascular lineage. Then, by using a microarray-based approach, we followed their gene expression during differentiation. We compared the transcriptome of undifferentiated CD34+ cells to those induced at two stages of differentiation (i.e., day three and day fourteen), with human cardiomyocyte progenitor cells (CMPCs), as well as cardiomyocytes as controls. Interestingly, in the treated cells, we observed an increase in the expressions of the main regulators usually present in cardiovascular cells. We identified cell surface markers of the cardiac mesoderm, such as kinase insert domain receptor (KDR) and the cardiogenic surface receptor Frizzled 4 (FZD4), induced in the differentiated cells in comparison to undifferentiated CD34+ cells. The Wnt and TGF-β pathways appeared to be involved in this activation. This study underlined the real capacity of effectively stimulated CD34+ SCs to express cardiac markers and, once induced, allowed the identification of markers that are known to be involved in vascular and early cardiogenesis, demonstrating their potential priming towards cardiovascular cells. These findings could complement their paracrine positive effects known in cell therapy for heart disease and may help improve the efficacy and safety of using ex vivo expanded CD34+ SCs.
Molecular Dynamic Simulations Reveal the Activation Mechanisms of Oxidation-Induced TRPV1
Authors: Chu Yanyan , Zhang Huanhuan , Yang Mengke , Yu Rilei
Published: June 2023

Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel, can be directly activated by oxidants through cysteine modification. However, the patterns of cysteine modification are unclear. Structural analysis showed that the free sulfhydryl groups of residue pairs C387 and C391 were potentially oxidized to form a disulfide bond, which is expected to be closely related to the redox sensing of TRPV1. To investigate if and how the redox states of C387 and C391 activate TRPV1, homology modeling and accelerated molecular dynamic simulations were performed. The simulation revealed the conformational transfer during the opening or closing of the channel. The formation of a disulfide bond between C387 and C391 leads to the motion of pre-S1, which further propagates conformational change to TRP, S6, and the pore helix from near to far. Residues D389, K426, E685–Q691, T642, and T671 contribute to the hydrogen bond transfer and play essential roles in the opening of the channel. The reduced TRPV1 was inactivated mainly by stabilizing the closed conformation. Our study elucidated the redox state of C387–C391 mediated long-range allostery of TRPV1, which provided new insights into the activation mechanism of TRPV1 and is crucial for making significant advances in the treatment of human diseases.
Molecular Dynamics Simulations of HPr Proteins from a Thermophilic and a Mesophilic Organism: A Comparative Thermal Study
Authors: Gómez-Flores Ana K. , López-Pérez Edgar , Alas-Guardado Salomón J.
Published: June 2023

The histidine-containing phosphocarrier (HPr) is a monomeric protein conserved in Gram-positive bacteria, which may be of mesophilic or thermophilic nature. In particular, the HPr protein from the thermophilic organism B. stearothermophilus is a good model system for thermostability studies, since experimental data, such as crystal structure and thermal stability curves, are available. However, its unfolding mechanism at higher temperatures is yet unclear at a molecular level. Therefore, in this work, we researched the thermal stability of this protein using molecular dynamics simulations, subjecting it to five different temperatures during a time span of 1 μs. The analyses of the structural parameters and molecular interactions were compared with those of the mesophilic homologue HPr protein from B. subtilis. Each simulation was run in triplicate using identical conditions for both proteins. The results showed that the two proteins lose stability as the temperature increases, but the mesophilic structure is more affected. We found that the salt bridge network formed by the triad of Glu3-Lys62-Glu36 residues and the salt bridge made up of Asp79-Lys83 ion pair are key factors to keep stable the thermophilic protein, maintaining the hydrophobic core protected and the structure packed. In addition, these molecular interactions neutralize the negative surface charge, acting as “natural molecular staples”.
Ganglioside GM1 and the Central Nervous System
Authors: Guo Zhongwu
Published: June 2023

GM1 is one of the major glycosphingolipids (GSLs) on the cell surface in the central nervous system (CNS). Its expression level, distribution pattern, and lipid composition are dependent upon cell and tissue type, developmental stage, and disease state, which suggests a potentially broad spectrum of functions of GM1 in various neurological and neuropathological processes. The major focus of this review is the roles that GM1 plays in the development and activities of brains, such as cell differentiation, neuritogenesis, neuroregeneration, signal transducing, memory, and cognition, as well as the molecular basis and mechanisms for these functions. Overall, GM1 is protective for the CNS. Additionally, this review has also examined the relationships between GM1 and neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, GM1 gangliosidosis, Huntington’s disease, epilepsy and seizure, amyotrophic lateral sclerosis, depression, alcohol dependence, etc., and the functional roles and therapeutic applications of GM1 in these disorders. Finally, current obstacles that hinder more in-depth investigations and understanding of GM1 and the future directions in this field are discussed.
The Exosome-like Vesicles of Giardia Assemblages A, B, and E Are Involved in the Delivering of Distinct Small RNA from Parasite to Parasite
Authors: Natali Lautaro , Luna Pizarro Gabriel , Moyano Sofía , de la Cruz-Thea Benjamin , Musso Juliana , Rópolo Andrea S. , Eichner Norbert , Meister Gunter , Musri Melina M. , Feliziani Constanza , Touz María C.
Published: June 2023

The genetically related assemblages of the intestinal protozoa parasite Giardia lamblia are morphologically indistinguishable and are often derived from specific hosts. The Giardia assemblages are separated by large genetic distances, which might account for their relevant biological and pathogenic differences. In this work, we analyzed the RNAs cargo released into exosomal-like vesicles (ElVs) by the assemblages A and B, which differentially infect humans, and the assemblage E, which infects hoofed animals. The RNA sequencing analysis revealed that the ElVs of each assemblage contained distinct small RNA (sRNA) biotypes, suggesting a preference for specific packaging in each assemblage. These sRNAs were classified into three categories, ribosomal-small RNAs (rsRNAs), messenger-small RNAs (msRNAs), and transfer-small RNAs (tsRNAs), which may play a regulatory role in parasite communication and contribute to host-specificity and pathogenesis. Uptake experiments showed, for the first time, that ElVs were successfully internalized by the parasite trophozoites. Furthermore, we observed that the sRNAs contained inside these ElVs were first located below the plasma membrane but then distributed along the cytoplasm. Overall, the study provides new insights into the molecular mechanisms underlying the host-specificity and pathogenesis of G. lamblia and highlights the potential role of sRNAs in parasite communication and regulation.
Hormesis Responses of Photosystem II in Arabidopsis thaliana under Water Deficit Stress
Authors: Sperdouli Ilektra , Ouzounidou Georgia , Moustakas Michael
Published: June 2023

Since drought stress is one of the key risks for the future of agriculture, exploring the molecular mechanisms of photosynthetic responses to water deficit stress is, therefore, fundamental. By using chlorophyll fluorescence imaging analysis, we evaluated the responses of photosystem II (PSII) photochemistry in young and mature leaves of Arabidopsis thaliana Col-0 (cv Columbia-0) at the onset of water deficit stress (OnWDS) and under mild water deficit stress (MiWDS) and moderate water deficit stress (MoWDS). Moreover, we tried to illuminate the underlying mechanisms in the differential response of PSII in young and mature leaves to water deficit stress in the model plant A. thaliana. Water deficit stress induced a hormetic dose response of PSII function in both leaf types. A U-shaped biphasic response curve of the effective quantum yield of PSII photochemistry (ΦPSII) in A. thaliana young and mature leaves was observed, with an inhibition at MiWDS that was followed by an increase in ΦPSII at MoWDS. Young leaves exhibited lower oxidative stress, evaluated by malondialdehyde (MDA), and higher levels of anthocyanin content compared to mature leaves under both MiWDS (+16%) and MoWDS (+20%). The higher ΦPSII of young leaves resulted in a decreased quantum yield of non-regulated energy loss in PSII (ΦNO), under both MiWDS (−13%) and MoWDS (−19%), compared to mature leaves. Since ΦNO represents singlet-excited oxygen (1O2) generation, this decrease resulted in lower excess excitation energy at PSII, in young leaves under both MiWDS (−10%) and MoWDS (−23%), compared to mature leaves. The hormetic response of PSII function in both young and mature leaves is suggested to be triggered, under MiWDS, by the intensified reactive oxygen species (ROS) generation, which is considered to be beneficial for activating stress defense responses. This stress defense response that was induced at MiWDS triggered an acclimation response in A. thaliana young leaves and provided tolerance to PSII when water deficit stress became more severe (MoWDS). We concluded that the hormesis responses of PSII in A. thaliana under water deficit stress are regulated by the leaf developmental stage that modulates anthocyanin accumulation in a stress-dependent dose.
Chromatographic Scalable Method to Isolate Engineered Extracellular Vesicles Derived from Mesenchymal Stem Cells for the Treatment of Liver Fibrosis in Mice
Authors: Domínguez Luciana M. , Bueloni Bárbara , Cantero Ma. José , Albornoz Milagros , Pacienza Natalia , Biani Celeste , Luzzani Carlos , Miriuka Santiago , García Mariana , Atorrasagasti Catalina , Yannarelli Gustavo , Bayo Juan , Fiore Esteban , Mazzolini Guillermo
Published: June 2023

New therapeutic options for liver cirrhosis are needed. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have emerged as a promising tool for delivering therapeutic factors in regenerative medicine. Our aim is to establish a new therapeutic tool that employs EVs derived from MSCs to deliver therapeutic factors for liver fibrosis. EVs were isolated from supernatants of adipose tissue MSCs, induced-pluripotent-stem-cell-derived MSCs, and umbilical cord perivascular cells (HUCPVC-EVs) by ion exchange chromatography (IEC). To produce engineered EVs, HUCPVCs were transduced with adenoviruses that code for insulin-like growth factor 1 (AdhIGF-I-HUCPVC-EVs) or green fluorescent protein. EVs were characterized by electron microscopy, flow cytometry, ELISA, and proteomic analysis. We evaluated EVs’ antifibrotic effect in thioacetamide-induced liver fibrosis in mice and on hepatic stellate cells in vitro. We found that IEC-isolated HUCPVC-EVs have an analogous phenotype and antifibrotic activity to those isolated by ultracentrifugation. EVs derived from the three MSCs sources showed a similar phenotype and antifibrotic potential. EVs derived from AdhIGF-I-HUCPVC carried IGF-1 and showed a higher therapeutic effect in vitro and in vivo. Remarkably, proteomic analysis revealed that HUCPVC-EVs carry key proteins involved in their antifibrotic process. This scalable MSC-derived EV manufacturing strategy is a promising therapeutic tool for liver fibrosis.
Design, Pharmacological Characterization, and Molecular Docking of Minimalist Peptidomimetic Antagonists of α4β1 Integrin
Authors: Baiula Monica , Anselmi Michele , Musiani Francesco , Ghidini Alessia , Carbone Jacopo , Caligiana Alberto , Maurizio Andrea , Spampinato Santi , Gentilucci Luca
Published: June 2023

Integrin receptors mediate cell–cell interactions via the recognition of cell-adhesion glycoproteins, as well as via the interactions of cells with proteins of the extracellular matrix, and upon activation they transduce signals bi-directionally across the cell membrane. In the case of injury, infection, or inflammation, integrins of β2 and α4 families participate in the recruitment of leukocytes, a multi-step process initiated by the capturing of rolling leukocytes and terminated by their extravasation. In particular, α4β1 integrin is deeply involved in leukocyte firm adhesion preceding extravasation. Besides its well-known role in inflammatory diseases, α4β1 integrin is also involved in cancer, being expressed in various tumors and showing an important role in cancer formation and spreading. Hence, targeting this integrin represents an opportunity for the treatment of inflammatory disorders, some autoimmune diseases, and cancer. In this context, taking inspiration from the recognition motives of α4β1 integrin with its natural ligands FN and VCAM-1, we designed minimalist α/β hybrid peptide ligands, with our approach being associated with a retro strategy. These modifications are expected to improve the compounds’ stability and bioavailability. As it turned out, some of the ligands were found to be antagonists, being able to inhibit the adhesion of integrin-expressing cells to plates coated with the natural ligands without inducing any conformational switch and any activation of intracellular signaling pathways. An original model structure of the receptor was generated using protein–protein docking to evaluate the bioactive conformations of the antagonists via molecular docking. Since the experimental structure of α4β1 integrin is still unknown, the simulations might also shed light on the interactions between the receptor and its native protein ligands.
Bisphenol S Reduces Pig Spermatozoa Motility through Different Intracellular Pathways and Mechanisms than Its Analog Bisphenol A
Authors: Torres-Badia Mercedes , Martin-Hidalgo David , Serrano Rebeca , Garcia-Marin Luis J. , Bragado Maria J.
Published: June 2023

Bisphenol A (BPA: 2,3-bis (4-hydroxyphenyl) propane) is an environmental chemical widely used in the manufacturing of epoxy polymers and many thermoplastic consumer products. Serious concerns about its safety led to the development of analogs, such as BPS (4-hydroxyphenyl sulfone). Very limited studies about BPS’s impact on reproduction, specifically in spermatozoa, exist in comparison with BPA. Therefore, this work aims to study the in vitro impact of BPS in pig spermatozoa in comparison with BPA, focusing on sperm motility, intracellular signaling pathways and functional sperm parameters. We have used porcine spermatozoa as an optimal and validated in vitro cell model to investigate sperm toxicity. Pig spermatozoa were exposed to 1 and 100 μM BPS or BPA for 3 and 20 h. Both bisphenol S and A (100 μM) significantly reduce pig sperm motility in a time-dependent manner, although BPS exerts a lower and slower effect than BPA. Moreover, BPS (100 μM, 20 h) causes a significant increase in the mitochondrial reactive species, whereas it does not affect sperm viability, mitochondrial membrane potential, cell reactive oxygen species, GSK3α/β phosphorylation or phosphorylation of PKA substrates. However, BPA (100 μM, 20 h) leads to a decrease in sperm viability, mitochondrial membrane potential, GSK3β phosphorylation and PKA phosphorylation, also causing an increase in cell reactive oxygen species and mitochondrial reactive species. These intracellular effects and signaling pathways inhibited might contribute to explaining the BPA-triggered reduction in pig sperm motility. However, the intracellular pathways and mechanisms triggered by BPS are different, and the BPS-caused reduction in motility can be only partially attributed to an increase in mitochondrial oxidant species.
The S100B Protein: A Multifaceted Pathogenic Factor More Than a Biomarker
Authors: Michetti Fabrizio , Clementi Maria Elisabetta , Di Liddo Rosa , Valeriani Federica , Ria Francesco , Rende Mario , Di Sante Gabriele , Romano Spica Vincenzo
Published: June 2023

S100B is a calcium-binding protein mainly concentrated in astrocytes in the nervous system. Its levels in biological fluids are recognized as a reliable biomarker of active neural distress, and more recently, mounting evidence points to S100B as a Damage-Associated Molecular Pattern molecule, which, at high concentration, triggers tissue reactions to damage. S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease. In addition, in experimental models of diseases such as Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic and vascular acute neural injury, epilepsy, and inflammatory bowel disease, alteration of S100B levels correlates with the occurrence of clinical and/or toxic parameters. In general, overexpression/administration of S100B worsens the clinical presentation, whereas deletion/inactivation of the protein contributes to the amelioration of the symptoms. Thus, the S100B protein may be proposed as a common pathogenic factor in different disorders, sharing different symptoms and etiologies but appearing to share some common pathogenic processes reasonably attributable to neuroinflammation.
Smooth Muscle-Alpha Actin R149C Pathogenic Variant Downregulates Integrin Recruitment at Cell-Matrix Adhesions and Decreases Cellular Contractility
Authors: Ojha Krishna R. , Kim Hyoseon , Padgham Samuel , Hopkins Laura , Zamen Robert J. , Chattopadhyay Abhijnan , Han Gang , Milewicz Dianna M. , Massett Michael P. , Trache Andreea
Published: June 2023

Thoracic aortic aneurysm is found in patients with ACTA2 pathogenic variants. ACTA2 missense variants are associated with impaired aortic smooth muscle cell (SMC) contraction. This study tested the hypothesis that the Acta2R149C/+ variant alters actin isoform expression and decreases integrin recruitment, thus, reducing aortic contractility. Stress relaxation measurements in thoracic aortic rings showed two functional regimes with a reduction of stress relaxation in the aorta from Acta2R149C/+ mice at low tension, but not at high tension values. Contractile responses to phenylephrine and potassium chloride were 50% lower in Acta2R149C/+ mice than in wild-type (WT) mice. Additionally, SMC were immunofluorescently labeled for specific proteins and imaged by confocal or total internal reflection fluorescence microscopy. The quantification of protein fluorescence of Acta2R149C/+ SMC showed a downregulation in smooth muscle α-actin (SMα-actin) and a compensatory upregulation of smooth muscle γ-actin (SMγ-actin) compared to WT cells. These results suggest that downregulation of SMα-actin leads to reduced SMC contractility, while upregulation of SMγ-actin may lead to increased SMC stiffness. Decreased α5β1 and α2β1 integrin recruitment at cell-matrix adhesions further reduce the ability of mutant cells to participate in cell-matrix crosstalk. Collectively, the results suggest that mutant Acta2R149C/+ aortic SMC have reduced contractility and interaction with the matrix, which are potential long-term contributing factors to thoracic aortic aneurysms.
Analytical Model for Evaluating the Reliability of Vias and Plated Through-Hole Pads on PCBs
Authors: Korobkov Maksim A. , Vasilyev Fedor V. , Khomutskaya Olga V.
Published: June 2023

Currently, there is a need to increase the density of interconnections on printed circuit boards (PCBs). Does this mean that the only option for quality PCB manufacturing is to proportionally increase precision of equipment, or is there another way? One of the main constraints on increasing the density of PCB interconnections is posed by the transition holes. As the number of conductive layers increases, the number of vias increases and they cover a significant space on the PCB. On the other hand, reducing the size of the vias is limited by the capability of spatial alignment of the PCB stack during manufacturing. There are standards that set limits for the design of contact pads on a PCB (IPC-A-600G, IPC-6012B). However, depending on the precision of production, the contact pads may be of poor quality. This raises the issue of determining the reliability of a contact pad with defined parameters at the design stage, taking into account manufacturing capabilities. This research proposes an analytical method for evaluation of reliability of a via or plated through-hole based on calculation of its probability of production in accordance with the current standards. On the basis of the method, a model was developed both for the case of a contact pad without any conductors connected to it (nonfunctional contact pad) and for the real case with a connected conductor. The model estimates the probability of making an acceptable via for a given reliability class depending on parameters such as the conductor width (minimum permissible and usable), drilled hole diameter, and pad diameter, as well as the accuracy of the drilling operation. The analysis of the modeling results showed that for the real case, a reduction in the reliability class would insignificantly affect the probability of making an acceptable via due to the tight limitation on the connection place of the conductor and the contact pad. In conclusion, we propose an algorithm for determining the optimal parameters of teardrops to minimize the negative impact of the conductor on the reliability of the vias.
Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion
Authors: Kirsten Nora , Ohmes Julia , Mikkelsen Maria Dalgaard , Nguyen Thuan Thi , Blümel Martina , Wang Fanlu , Tasdemir Deniz , Seekamp Andreas , Meyer Anne S. , Fuchs Sabine
Published: June 2023

The endothelial cell lining creates an interface between circulating blood and adjoining tissue and forms one of the most critical barriers and targets for therapeutical intervention. Recent studies suggest that fucoidans, sulfated and fucose-rich polysaccharides from brown seaweed, show multiple promising biological effects, including anti-inflammatory properties. However, their biological activity is determined by chemical characteristics such as molecular weight, sulfation degree, and molecular structure, which vary depending on the source, species, and harvesting and isolation method. In this study, we investigated the impact of high molecular weight (HMW) fucoidan extract on endothelial cell activation and interaction with primary monocytes (MNCs) in lipopolysaccharide (LPS)-induced inflammation. Gentle enzyme-assisted extraction combined with fractionation by ion exchange chromatography resulted in well-defined and pure fucoidan fractions. FE_F3, with a molecular weight ranging from 110 to 800 kDa and a sulfate content of 39%, was chosen for further investigation of its anti-inflammatory potential. We observed that along with higher purity of fucoidan fractions, the inflammatory response in endothelial mono- and co-cultures with MNCs was reduced in a dose-dependent manner when testing two different concentrations. This was demonstrated by a decrease in IL-6 and ICAM-1 on gene and protein levels and a reduced gene expression of TLR-4, GSK3β and NF-kB. Expression of selectins and, consequently, the adhesion of monocytes to the endothelial monolayer was reduced after fucoidan treatment. These data indicate that the anti-inflammatory effect of fucoidans increases with their purity and suggest that fucoidans might be useful in limiting the inflammatory response of endothelial cells in cases of LPS-induced bacterial infection.
Anatomical Variants of Internal Carotid Artery—Results from a Retrospective Study
Authors: Cobzeanu Bogdan Mihail , Baldea Vasilica , Costan Victor Vlad , Cobzeanu Mihail Dan , Palade Octavian Dragos , Gheorghe Liliana , Radulescu Luminita , Severin Florentina , Lupascu Ursulescu Corina , Bandol Geanina , Martu Cristian , Rosu Andrei Mihail , Cobzeanu Maria Luiza
Published: June 2023

Background and Objectives: The internal carotid artery (ICA) is a vascular structure that can be easily injured during sinus endoscopic procedures, and surgeons should be familiar with its anatomic variants. The aim of this study was to describe the anatomical variations in the internal carotid artery in relationship to sphenoidal sinuses, using computed tomography (CT). Materials and Methods: In this retrospective study, we evaluated the variations of the ICA in relationship to sphenoidal sinuses in a cohort of 600 patients who were assessed between January 2020 and December 2022 in ‘Saint Spiridon’ Emergency Hospital, Iasi, Romania. Descriptive statistics were used to characterize our data. Results: The most prevalent anatomical variant was represented by intrasinusal septa with posterior insertion on the ICA (58.6%), followed by procident ICA (58%) and dehiscent ICA (52%). We could not find any statistical significance regarding demographic characteristics among groups. Conclusions: A thorough CT examination should be performed before functional endoscopic sinus surgery, with the identification of anatomical variants of the ICA, in order to prevent its injury with potentially fatal consequences.
Comparative Study of Long-Term Outcomes of Laparoscopic Liver Resection versus Radiofrequency Ablation for Single Small Hepatocellular Carcinoma Located in Left Lateral Segments of the Liver
Authors: Kang MeeYoung , Cho Jai Young , Han Ho-Seong , Yoon Yoo-Seok , Lee Hae Won , Lee Boram , Park Yeshong , Kim Jinju , Yoon Chang Jin
Published: June 2023

Background and Objectives: Laparoscopic liver resection (LLR) is now widely recognized as the primary surgical option for hepatocellular carcinomas (HCC) smaller than 3 cm located in the left lateral segment of the liver. Nevertheless, there is a scarcity of studies comparing laparoscopic liver resection with radiofrequency ablation (RFA) in these cases. Materials and Methods: We retrospectively compared the short- and long-term outcomes of Child–Pugh class A patients who underwent LLR (n = 36) or RFA (n = 40) for a newly diagnosed single small (≤3 cm) HCC located in the left lateral segment of the liver. Results: Overall survival (OS) was not significantly different between the LLR and RFA groups (94.4% vs. 80.0%, p = 0.075). However, disease-free survival (DFS) was better in the LLR group than in the RFA group (p < 0.001), with 1-, 3-, and 5-year DFS rates of 100%, 84.5%, and 74.4%, respectively, in the LLR group vs. 86.9%, 40.2%, and 33.4%, respectively, in the RFA group. The hospital stay was significantly shorter in the RFA group than in the LLR (2.4 vs. 4.9 days, p < 0.001). The overall complication rate was higher in the RFA group than in the LLR group (15% vs. 5.6%). In patients with an α-fetoprotein level of ≥20 ng/mL, the 5-year OS (93.8% vs. 50.0%, p = 0.031) and DFS (68.8% vs. 20.0%, p = 0.002) rates were greater in the LLR group. Conclusions: LLR showed superior OS and DFS compared to RFA in patients with a single small HCC situated in the left lateral segment of the liver. LLR can be considered for patients with an α-fetoprotein level of ≥20 ng/mL.
Engaging “Care” Behaviors in Support of Employee and Organizational Wellbeing through Complexity Leadership Theory
Authors: Kolga Merike
Published: June 2023

During the COVID-19 pandemic, the attributes of nurturing, empathy, and relating rather than directing moved into the spotlight as important skills for leadership. These skills are representative of the concept of “care” that is often associated with women’s or feminine leadership. The importance of care as a component of leadership had not received significant attention in the leadership literature until the pandemic brought the need for care onto center stage. This article argues that care will continue to be an important attribute of leadership and an essential attribute of an androgynous leadership style—that includes behaviors typically classified as male and those behaviors typically classed as female—that is needed to navigate the increasing complexity of the world most effectively. The article further argues that complexity leadership theory provides the most appropriate leadership approach through which complex adaptive organizations can initiate and foster the development of “care” behaviors as part of an androgynous approach to leadership which produces system-wide benefits in complex systems more capable of addressing the global challenges of the climate crisis and increased environmental disasters, future pandemics, local wars, terrorist attacks, and other phenomena.
Efficient pH-Responsive Nano-Drug Delivery System Based on Dynamic Boronic Acid/Ester Transformation
Authors: Chen Weijun , Xie Wanxuan , Zhao Guangkuo , Shuai Qi
Published: June 2023

Chemotherapy is currently one of the most widely used treatments for cancer. However, traditional chemotherapy drugs normally have poor tumor selectivity, leading to insufficient accumulation at the tumor site and high systemic cytotoxicity. To address this issue, we designed and prepared a boronic acid/ester-based pH-responsive nano-drug delivery system that targets the acidic microenvironment of tumors. We synthesized hydrophobic polyesters with multiple pendent phenylboronic acid groups (PBA-PAL) and hydrophilic PEGs terminated with dopamine (mPEG-DA). These two types of polymers formed amphiphilic structures through phenylboronic ester linkages, which self-assembled to form stable PTX-loaded nanoparticles (PTX/PBA NPs) using the nanoprecipitation method. The resulting PTX/PBA NPs demonstrated excellent drug encapsulation efficiency and pH-triggered drug-release capacity. In vitro and in vivo evaluations of the anticancer activity of PTX/PBA NPs showed that they improved the pharmacokinetics of drugs and exhibited high anticancer activity while with low systemic toxicity. This novel phenylboronic acid/ester-based pH-responsive nano-drug delivery system can enhance the therapeutic effect of anticancer drugs and may have high potential for clinical transformations.
Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products
Authors: Kravljanac Pavle , Anderson Edward A.
Published: June 2023

Triterpenoid natural products from the Schisandraceae family have long presented a significant synthetic challenge. Lancifodilactone I, a member of the family not previously synthesized, was identified as a key natural product target, from which many other members could be synthesized. We envisaged that the core ring system of lancifodilactone I could be accessed by a strategy involving palladium-catalysed cascade cyclisation of a bromoenynamide, via carbopalladation, Suzuki coupling and 8π-electrocyclisation, to synthesize the core 7,8-fused ring system. Exploration of this strategy on model systems resulted in efficient syntheses of 5,6- and 5,8-fused systems in high yields, which represent the first such cyclisation where the ynamide nitrogen atom is ‘external’ to the forming ring system. The enamide functionality resident in the cascade cyclisation product was found to be less nucleophilic than the accompanying tri-/tetrasubstituted alkene(s), enabling regioselective oxidations. Application of this strategy to 7,6-, and 7,8-fused systems, and ultimately the ‘real’ substrate, was ultimately thwarted by the difficulty of 7-membered ring closure, leading to side product formation. Nevertheless, a tandem bromoenynamide carbopalladation, Suzuki coupling and 6/8π-electrocyclisation was shown to be a highly efficient tactic for the formation of bicyclic enamides, which may find applications in other synthetic contexts.
Benzoylaconitine Alleviates Progression of Psoriasis via Suppressing STAT3 Phosphorylation in Keratinocytes
Authors: Li Yuanbo , Guo Dandan , Wang Qianqian , Li Aifang , Yin Sugai , Li Shuxuan , Li Yalan , Wang Baiyan , Guo Tao , Feng Shuying
Published: June 2023

Psoriasis is a chronic and multifactorial skin disease which is caused by inflammatory infiltrates, keratinocyte hyperproliferation, and accumulation of immune cells. As part of the Aconitum species, Benzoylaconitine (BAC) shows potential antiviral, anti-tumor, and anti-inflammatory effects. In this study, we investigated the effects and mechanisms of BAC on tumor necrosis factor-alpha (TNF-α)/LPS-induced HaCaT keratinocytes in a imiquimod(IMQ)-induced mice model. The results showed that BAC could relieve the symptoms of psoriasis by inhibiting cell proliferation, the release of inflammatory factors, and the accumulation of Th17 cells, while no obvious effect on cell viability and safety was observed both in vitro and in vivo. Additionally, BAC can markedly inhibit the protein and mRNA levels of inflammatory cytokines in TNF-α/LPS-induced HaCaT keratinocytes by inhibiting the phosphorylation of STAT3. In brief, our data indicated that BAC could alleviate the progression of psoriasis and may be a potential therapeutic agent for treating psoriasis in clinical practice.