bluuebunny/crossref_metadata_2025 huggingface dataset:
Silica–Chitosan Composite Aerogels for Thermal Insulation and Adsorption
Authors: Mei Xueli , Li Shihao , Chen Yaoyao , Huang Xueli , Cao Yali , Guro Vitaliy P. , Li Yizhao
Published: May 2023

The dissipation of energy in the form of heat causes a huge energy loss across the globe. Thermal insulation materials which reduce heat loss can alleviate the energy crisis. Among many thermal insulation materials, silica aerogels (SAs) have attracted extensive attention due to their high surface area, low density and low thermal conductivity. However, the applications of SAs are restricted by their mechanical fragility. In this paper, a series of different ratios of silica–chitosan composite aerogels (SCAs) were prepared by mixing sodium silicate aqueous solution and chitosan solution followed by freeze drying. The surface morphology of SAs, CAs and SCAs was studied by scanning electron microscopy (SEM). The specific surface area, pore volume and pore size of the composite aerogels were studied by N2 adsorption–desorption isotherms. The thermal conductivities, chemical structures, thermal stabilities and hydrophobicities of SAs, CAs and SCAs were tested and analyzed. In addition, the adsorption properties of SCAs were measured using different organic solvents. The results reveal that when the proportion of sodium silicate aqueous solution and chitosan solution is 1:1, the obtained SCA−1/1 has the best performance, with a low thermal conductivity of 0.0369 W/m·K, a large specific surface area of 374.7 m2/g, and good thermal stability. In addition, the prepared SCAs also have good hydrophobicity and absorption properties, with adsorption capacities of 6.7–9.4 g/g, which show great application potential in the fields of insulation and adsorption.
Olaparib versus Placebo in Maintenance Treatment of Germline BRCA-Mutated Metastatic Pancreatic Cancer: A Cost–Utility Analysis from the Canadian Public Payer’s Perspective
Authors: Mirzayeh Fashami Fatemeh , Levine Mitchell , Xie Feng , Blackhouse Gordon , Tarride Jean-Eric
Published: May 2023

Pancreatic cancer has an annual incidence of 2/10,000 in Canada, with a one-year mortality rate greater than 80%. In the absence of a cost-effectiveness analysis in Canada, this study’s objective was to assess the cost-effectiveness of olaparib versus a placebo in adult patients with deleterious or suspected deleterious BRCA metastatic pancreatic adenocarcinoma, who did not show any progression for at least 16 weeks with first-line platinum-based chemotherapy. A partitioned survival model with a 5-year time horizon was adopted to estimate the costs and effectiveness. All of the costs were extracted from the public payer’s available resources, effectiveness data were obtained from the POLO trial, and Canadian studies were used for utility inputs. Probabilistic sensitivity analyses and scenario analyses were performed. The total costs of olaparib and the placebo over five years were CAD 179,477 and CAD 68,569, with overall quality-adjusted life-years (QALYs) of 1.70 and 1.36, respectively. The incremental cost-effectiveness ratio (ICER) of the olaparib group compared with the placebo was CAD 329,517 per QALY. With a commonly cited willingness to pay (WTP) threshold of CAD 50,000 per QALY, the drug does not achieve acceptable cost-effectiveness mainly due to the high price of the medication and insufficient impact on the overall survival of patients with metastatic pancreatic cancer.
Phylogeny of Scissicauda Species, with Eight New Species, including the First Photinini Fireflies with Biflabellate Antennae (Coleoptera: Lampyridae)
Authors: Zeballos Leandro Felipe , Roza André Silva , Campello-Gonçalves Lucas , Vaz Stephanie , Da Fonseca Cláudio Ruy Vasconcelos , Rivera Sara Cristina , da Silveira Luiz Felipe Lima
Published: May 2023

Photinini is the largest tribe of Lampyrinae fireflies, with over 30 genera and nearly 750 species, and includes taxa where adults may or may not have light organs. A focus on taxa with bioluminescent adults left the taxonomy of dark fireflies in poor condition compared to taxa with lit adults. A recent phylogenetic study based on molecular data supported the transfer of Scissicauda McDermott, 1964—traditionally placed in Amydetinae due to the flabellate antenna of its type species—to Photinini at a branch sided with Pyropyga Motschulsky, 1852 and Pyractonema Solier, 1849. Such placement had never been recovered before in morphology-based studies, and the consequences for the interpretation of character evolution in this lineage are yet to be addressed. Moreover, Scissicauda was previously thought to be endemic to the Atlantic Forest. Here, through phylogenetic analyses of 38 taxa and 108 morphological characters, we (i) expand on the concept of Scissicauda to include S. antennata sp. nov., S. asymmetrica sp. nov., S. aurata sp. nov., S. biflabellata sp. nov., S. gomesi sp. nov., S. jamari sp. nov., S. neyi sp. nov., S. truncata sp. nov., and (ii) transfer Lucidota malleri Pic, 1935 and, therefore, S. malleri comb. nov. We also recover Pyropyga + Pyractonema as sister to Scissicauda + Haplocauda, providing the first morphological evidence for their sisterhood. Noteworthy, the new species S. biflabellata sp. nov. and S. asymmetrica sp. nov. stand out as the first known Photinini species with biflabellate antennae. In addition, our study reports the first Scissicauda species in the Amazon (S. antennata sp. nov., S. aurata sp. nov., S. gomesi sp. nov., S. jamari sp. nov., and S. truncata sp. nov.) and Cerrado biome (S. neyi sp. nov.). Our study highlights the value of continued sampling and phylogenetic analyses of South American fireflies towards a revised classification and deeper understanding of this lineage.
Irruption Theory: A Novel Conceptualization of the Enactive Account of Motivated Activity
Authors: Froese Tom
Published: May 2023

Cognitive science is lacking conceptual tools to describe how an agent’s motivations, as such, can play a role in the generation of its behavior. The enactive approach has made progress by developing a relaxed naturalism, and by placing normativity at the core of life and mind; all cognitive activity is a kind of motivated activity. It has rejected representational architectures, especially their reification of the role of normativity into localized “value” functions, in favor of accounts that appeal to system-level properties of the organism. However, these accounts push the problem of reification to a higher level of description, given that the efficacy of agent-level normativity is completely identified with the efficacy of non-normative system-level activity, while assuming operational equivalency. To allow normativity to have its own efficacy, a new kind of nonreductive theory is proposed: irruption theory. The concept of irruption is introduced to indirectly operationalize an agent’s motivated involvement in its activity, specifically in terms of a corresponding underdetermination of its states by their material basis. This implies that irruptions are associated with increased unpredictability of (neuro)physiological activity, and they should, hence, be quantifiable in terms of information-theoretic entropy. Accordingly, evidence that action, cognition, and consciousness are linked to higher levels of neural entropy can be interpreted as indicating higher levels of motivated agential involvement. Counterintuitively, irruptions do not stand in contrast to adaptive behavior. Rather, as indicated by artificial life models of complex adaptive systems, bursts of arbitrary changes in neural activity can facilitate the self-organization of adaptivity. Irruption theory therefore, makes it intelligible how an agent’s motivations, as such, can make effective differences to their behavior, without requiring the agent to be able to directly control their body’s neurophysiological processes.
Conjugate Radiation and Convection Heat Transfer Analysis in Solar Cooker Cavity Using a Computational Approach
Authors: Sarangi Abhisek , Sarangi Asish , Sahoo Sudhansu Sekhar , Mallik Ramesh Kumar , Awad Mohamed M.
Published: May 2023

The heat loss caused by radiation and persistently laminar natural convection in a solar cooker cavity that has a rectangular cavity or a trapezoidal cavity are computationally explored in this paper. The hot bottom and the adiabatic side wall are both taken into account. Two possibilities are considered for the top wall: first, a cold wall, and, second, losses from wind-induced convection and radiation. The parameters of heat loss in various depth cavities have been investigated along with a variety of external heat transfer coefficient values above the glass surface were simulated. The emissivity of the bottom surface, the absolute temperature ratio, on heat loss from the considered geometries, are also calculated. Analysis of the cavity’s flow pattern and isotherms at different depths has been conducted, and it is discovered that the total rate of heat transfer from the top wall increases as the bottom wall’s emissivity, the absolute temperature ratio, the Rayleigh number, and the external Nusselt number all increase. While radiation heat transfer increases monotonically, convective heat transfer rates shift slightly as these values rise at different emissivities of the bottom, and the opposite occurs when Ra increases at the same emissivity. Furthermore, it has been discovered that as the aspect ratio of the cavity increases, the overall Nusselt number decreases. A trapezoidal cavity has a faster rate of heat transfer than a rectangular cavity for the same parameters. Generic empirical correlations were developed for the total average Nusselt number concerning all influencing parameters.
Carnot Battery Based on Brayton Supercritical CO2 Thermal Machines Using Concentrated Solar Thermal Energy as a Low-Temperature Source
Authors: Linares José Ignacio , Martín-Colino Arturo , Arenas Eva , Montes María José , Cantizano Alexis , Pérez-Domínguez José Rubén
Published: May 2023

Carnot batteries store surplus power as heat. They consist of a heat pump, which upgrades a low-temperature thermal energy storage, a high-temperature storage system for the upgraded thermal energy, and a heat engine that converts the stored high-temperature thermal energy into power. A Carnot battery is proposed based on supercritical CO2 Brayton thermodynamic cycles. The low-temperature storage is a two-tank molten salt system at 380 °C/290 °C fed by a field of parabolic trough collectors. The high-temperature storage consists of another two-tank molten salt system at 589 °C/405 °C. Printed circuit heat exchangers would be required to withstand the high pressure of the cycles, but shell and tube heat exchangers are proposed instead to avoid clogging issues with molten salts. The conventional allocation of high-temperature molten salt heat exchangers is then modified. Using solar energy to enhance the low-temperature thermal source allowed a round-trip efficiency of 1.15 (COP of 2.46 and heat engine efficiency of 46.5%), thus increasing the stored power. The basic configuration has a levelised cost of storage of USD 376/MWh while replacing the shell and tube heat exchangers with hybrid printed circuit heat exchangers is expected to lower the cost to USD 188/MWh.
Assessing and Mapping Forest Functions through a GIS-Based, Multi-Criteria Approach as a Participative Planning Tool: An Application Analysis
Authors: Cammerino Anna Rita Bernadette , Ingaramo Michela , Piacquadio Lorenzo , Monteleone Massimo
Published: May 2023

A relatively new planning tool in Italy is the Local Forest Plan, which stands at a broader level in the land planning scale compared to the Forest Management Plan but at a finer scale considering a Regional or even National Forest Plan. This intermediate scale was considered the most appropriate for working out a planning process based on a multi-criteria assessment of forest functions. The proper functioning of forest ecosystems can provide services conceived as benefits people can obtain through ecological processes that sustain and satisfy essential needs of human life. Four particular forest functions providing services were identified: protective, productive, naturalistic and touristic, respectively. A set of functional criteria, as well as attributes within criteria, were recognized to perform an “Analytic Hierarchy Process” (AHP). A specific application of this methodological approach was selected as a case study. This multi-criteria decision-making process involved the participation of five selected experts in a preliminary phase, followed by the participation of thirty representative stakeholders who contributed to the forest planning process and the subsequent selection of actions to be taken. Data related to forest types and management, physical and morphological features of the forested terrain and infrastructure such as forest roads, touristic trails and hiking pathways, together with natural protected areas or wildlife preservation areas, were explicitly located in space by using a “geographical information service” (GIS) software. The combined application of AHP and GIS can be considered as a significant methodological innovation presented in the case study, together with the implementation of a participative process aimed at the management of forest resources and the creation of possible new professional and entrepreneurial forest activities for the benefit of the entire residential community.
Variation in Leaf Functional and Plant Defense Traits of Introduced Eucalyptus Species across Environmental Gradients in Their New Range in Southern China
Authors: Liu Hui , Rutherford Susan , Wan Justin Siu Hung , Liu Jinhui , Zhang Jin , Afzal Muhammad Rahil , Du Daolin , Rossetto Maurizio
Published: May 2023

Due to the rapid development of China’s economy, the demand for wood is steadily increasing. Eucalyptus species have been introduced in large quantities because of their fast growth, strong adaptability, and wide utility. To understand the phenological changes in introduced Eucalyptus in its new range, we carried out a field investigation to examine leaf functional and chemical defense traits of three introduced species (E. saligna, E. grandis and E. robusta) over latitudinal and altitudinal gradients in southern China. We sampled multiple stands of each species, and measured the leaf physical characteristics (e.g., leaf width, leaf thickness, and specific leaf area [SLA]), leaf nitrogen (N) and phosphorus (P) content, and phenolic compounds. We found that many functional traits (e.g., leaf size and thickness) decreased at lower latitudes, especially in E. grandis, possibly to reduce heat and water loss under higher temperatures. In E. grandis, we found that leaf P was lower at higher latitudes and altitude, and phenolics increased with elevation, while in E. robusta, both leaf N and P decreased with altitude. These findings suggested that both species were more conservative in resource allocation, with E. grandis possessing enhanced chemical defenses in response to the conditions experienced at higher elevations. In addition, we found the tree populations at the northern range limit of E. robusta had lower SLA, suggesting a more conservative growth strategy, In contrast, small populations in the northern part of the ranges of E. grandis had higher SLA, indicating range expansion at the edge of the species’ geographic distribution. Overall, it is particularly important to consider intraspecific trait differences across wide geographic areas when studying the spread of invasive species in the new range.
Microbiological and Technological Insights on Anaerobic Digestion of Animal Manure: A Review
Authors: Song Yapeng , Qiao Wei , Westerholm Maria , Huang Guangqun , Taherzadeh Mohammad J. , Dong Renjie
Published: May 2023

Anaerobic digestion of animal manure results in the production of renewable energy (biogas) and nutrient-rich biofertilizer. A further benefit of the technology is decreased greenhouse gas emissions that otherwise occur during manure storage. Since animal manure makes anaerobic digestion cost-efficient and further advance the technology for higher methane yields, it is of utmost importance to find strategies to improve bottlenecks such as the degradation of lignocellulose, e.g., in cattle manure, or to circumvent microbial inhibition by ammonia caused by the degradation of nitrogen compounds in, e.g., chicken, duck, or swine manure. This review summarizes the characteristics of different animal manures and provides insight into the underlying microbial mechanisms causing challenging problems with the anaerobic digestion process. A particular focus is put upon the retention time and organic loading rate in high-ammonia processes, which should be designed and optimized to support the microorganisms that tolerate high ammonia conditions, such as the syntrophic acetate oxidizing bacteria and the hydrogenotrophic methanogens. Furthermore, operating managements used to stabilize and increase the methane yield of animal manure, including supporting materials, the addition of trace elements, or the incorporation of ammonia removal technologies, are summarized. The review is finalized with a discussion of the research needed to outline conceivable operational methods for the anaerobic digestion process of animal manure to circumvent process instability and improve the process performance.
An Implicit Numerical Method for the Riemann–Liouville Distributed-Order Space Fractional Diffusion Equation
Authors: Zhang Mengchen , Shen Ming , Chen Hui
Published: May 2023

This paper investigates a two-dimensional Riemann–Liouville distributed-order space fractional diffusion equation (RLDO-SFDE). However, many challenges exist in deriving analytical solutions for fractional dynamic systems. Efficient and reliable methods need to be explored for solving the RLDO-SFDE numerically. We develop an alternating direction implicit scheme and prove that the numerical method is unconditionally stable and convergent with an accuracy of O(σ2+ρ2+τ+hx+hy). After employing an extrapolated technique, the convergence order is improved to second order in time and space. Furthermore, a fast algorithm is constructed to reduce computational costs. Two numerical examples are presented to verify the effectiveness of the numerical methods. This study may provide more possibilities for simulating diffusion complexities by fractional calculus.
Freezing Does Not Alter Sperm Telomere Length despite Increasing DNA Oxidation and Fragmentation
Authors: Gouhier Charlène , Pons-Rejraji Hanae , Dollet Sandra , Chaput Laure , Bourgne Céline , Berger Marc , Pereira Bruno , Tchirkov Andrei , Brugnon Florence
Published: May 2023

Correlations were reported between sperm telomere length (STL) and male fertility, sperm DNA fragmentation, and oxidation. Sperm freezing is widely used for assisted reproductive techniques, fertility preservation, and sperm donation. However, its impact on STL remains unknown. For this study, semen surplus from patients who underwent routine semen analysis were used. The impact of slow freezing on STL was analyzed by performing qPCR before and after freezing. Sperm populations with different STL were evaluated using Q-FISH. The relationship between sperm DNA oxidation, DNA fragmentation, and STL was assessed in fresh and frozen sperm samples. No significant impact of slow freezing on STL was observed, neither measured by qPCR nor Q-FISH. However, Q-FISH allowed for the distinguishing of sperm populations with different STLs within individual sperm samples. Slow freezing induced different STL distributions for some of the analyzed sperm samples, but no correlation was found between STL and sperm DNA fragmentation or oxidation. Slow freezing does not alter STL despite increasing sperm DNA oxidation and fragmentation. As STL alterations could be transmitted to offspring, the lack of impact of the slow freezing method on STL ensures the safety of this procedure.
Impact of COVID-19 on Adherence to Treatment in Patients with HIV
Authors: Carbonero-Lechuga Pablo , Castrodeza-Sanz Javier , Sanz-Muñoz Iván , Marqués-Sánchez Pilar , Eiros Jose M. , Dueñas-Gutiérrez Carlos , Prada-García Camino
Published: May 2023

In patients with human immunodeficiency virus (HIV), adherence to treatment is affected by the adverse effects of treatment, the presence of additional comorbidities, the complexity of dosage, and family and community support. However, one recent circumstance that was likely to have influenced therapeutic adherence was the COVID-19 pandemic and the applied containment measures. An observational retrospective study of a sample of patients with HIV was conducted to establish the relationship between sociodemographic, clinical, and pharmacological variables and therapeutic adherence before and after the pandemic. Adherence was measured using the validated simplified medication adherence questionnaire (SMAQ) and medication possession rate. A statistical analysis was performed to determine the mean, standard deviation, and median of the quantitative variables and the frequencies of the qualitative variables, and the relationship between the dependent and independent variables was analysed using the chi-squared test and Student’s t-test. No statistically significant differences were found between treatment adherence measured before and 22 months after the start of the pandemic. Sex, occupation, treatment regimen, viral load levels, and COVID-19 disease status did not influence adherence during either period. However, the age of patients with HIV had an impact on adherence during both periods (p = 0.008 and p = 0.002, respectively), with the age group under 45 years being less adherent. In addition, experiencing adverse drug reactions (ADRs) was shown to have an impact on adherence before the pandemic (p = 0.006) but not afterwards. The COVID-19 pandemic was not shown to have an impact on the degree of adherence to antiretroviral treatment in patients with HIV. Instead, adherence was influenced by patient age and ADR occurrence; therefore, measures must be taken in this regard. The SMAQ demonstrated sensitivity in assessing adherence.
Diverse Virulence Attributes of Pantoea alfalfae sp. nov. CQ10 Responsible for Bacterial Leaf Blight in Alfalfa Revealed by Genomic Analysis
Authors: Yao Bo , Huang Rong , Zhang Zhenfen , Shi Shangli
Published: May 2023

Alfalfa is widely grown worldwide for its excellent nutritional value. Pantoea species living in alfalfa seeds can easily spread over great distances with frequent trade. However, the pathogenic properties of this dangerous hitchhiker on alfalfa have not been evaluated. Here, we identified the taxonomic status of Pantoea strain CQ10 isolated from the interior of alfalfa seeds based on the whole genome sequence. The diverse virulence attributes of strain CQ10 during host infection were characterized through pathogenicity assays and functional and genomic analyses. We report that strain CQ10 belongs to a novel species in the genus Pantoea, which was phylogenetically close to Pantoea vagans and Pantoea agglomerans. Strain CQ10 caused bacterial leaf blight of alfalfa after inoculation from the roots. We found that strain CQ10 possesses a large number of pathogenic genes involved in shaping the virulence properties during bacteria–host interactions, including motility, biofilm, type VI secretion system, and nutrient acquisition. Compared with P. vagans and P. agglomerans, the unique virulence factors of strain CQ10 were mainly involved in motility and biofilm, which were confirmed by in vitro experiments. Taken together, our results suggest that strain CQ10 is the first Pantoea species to infect alfalfa, and it possesses diverse virulence attributes among which motility and biofilm may be the best weapons.
A New Unified Theory of Trigger Point Formation: Failure of Pre- and Post-Synaptic Feedback Control Mechanisms
Authors: Gerwin Robert D.
Published: May 2023

The origin of the myofascial trigger point (TrP), an anomalous locus in muscle, has never been well-described. A new trigger point hypothesis (the new hypothesis) presented here addresses this lack. The new hypothesis is based on the concept that existing myoprotective feedback mechanisms that respond to muscle overactivity, low levels of adenosine triphosphate, (ATP) or a low pH, fail to protect muscle in certain circumstances, such as intense muscle activity, resulting in an abnormal accumulation of intracellular Ca2+, persistent actin-myosin cross bridging, and then activation of the nociceptive system, resulting in the formation of a trigger point. The relevant protective feedback mechanisms include pre- and postsynaptic sympathetic nervous system modulation, modulators of acetylcholine release at the neuromuscular junction, and mutations/variants or post-translational functional alterations in either of two ion channelopathies, the ryanodine receptor and the potassium-ATP ion channel, both of which exist in multiple mutation states that up- or downregulate ion channel function. The concepts that are central to the origin of at least some TrPs are the failure of protective feedback mechanisms and/or of certain ion channelopathies that are new concepts in relation to myofascial trigger points.
Silencing of the Laccase (lacc2) Gene from Pleurotus ostreatus Causes Important Effects on the Formation of Toxocyst-like Structures and Fruiting Body
Authors: Armas-Tizapantzi Anahí , Martínez y Pérez José Luis , Fernández Francisco José , Mata Gerardo , Hernández-Cuevas Laura V. , Ortiz Ortiz Elvia , García Nieto Edelmira , Tomasini Araceli , Sierra-Palacios Edgar , Marcial-Quino Jaime , Montiel-González Alba Mónica
Published: May 2023

A wide variety of biological functions, including those involved in the morphogenesis process of basidiomycete fungi, have been attributed to laccase enzymes. In this work, RNA interference (RNAi) was used to evaluate the role of the laccase (lacc2) gene of Pleurotus ostreatus PoB. Previously, transformant strains of P. ostreatus were obtained and according to their level of silencing they were classified as light (T7), medium (T21) or severe (T26 and T27). The attenuation of the lacc2 gene in these transformants was determined by RT-PCR. Silencing of lacc2 resulted in a decrease in laccase activity between 30 and 55%, which depended on the level of laccase expression achieved. The silenced strains (T21, T26, and T27) displayed a delay in the development of mycelium on potato dextrose agar (PDA) medium, whereas in the cultures grown on wheat straw, we found that these strains were incapable of producing aerial mycelium, primordia, and fruiting bodies. Scanning electron microscopy (SEM) showed the presence of toxocyst-like structures. The highest abundance of these structures was observed in the wild-type (PoB) and T7 strains. However, the abundance of toxocysts decreased in the T21 and T26 strains, and in T27 they were not detected. These results suggest that the presence and abundance of toxocyst-like structures are directly related to the development of fruiting bodies. Furthermore, our data confirm that lacc2 is involved in the morphogenesis process of P. ostreatus.
Thermal Disorder in Finite-Length Carbon Nanowire
Authors: Wong C. H. , Buntov E. A. , Yip W. S. , To S. , Guseva M. B. , Zatsepin A. F.
Published: May 2023

Enhancement in chemisorption is one of the active research areas in carbon materials. To remedy the thermally degraded chemisorption occurring at high temperatures, we report a comprehensive study of kink structures in free-standing monoatomic carbon nanowires upon heating. Our Monte Carlo simulation considers multi-monoatomic carbon chains laterally interacting by van der Waals forces. Our study reveals that carbon nanowires maintain their linearity regardless of chain length at low temperatures, but this is not the case at high temperatures. Disordered kink structure is observed in short carbon chains, especially above the Peierls transition temperature. A severe kink structure may increase the possibility of attaching negatively charged atoms, thereby contributing to the development of next-generation materials for chemisorption at high temperatures. We have also provided an important indication that any physical property of the finite-length carbon chain predicted by ab initio calculation should reconsider the atomic rearrangement due to thermal instability at high temperatures.
Absolute Stereochemistry and Cytotoxic Effects of Vismione E from Marine Sponge-Derived Fungus Aspergillus sp. 1901NT-1.2.2
Authors: Girich Elena V. , Trinh Phan Thi Hoai , Nesterenko Liliana E. , Popov Roman S. , Kim Natalya Yu. , Rasin Anton B. , Menchinskaya Ekaterina S. , Kuzmich Aleksandra S. , Chingizova Ekaterina A. , Minin Artem S. , Ngoc Ngo Thi Duy , Van Tran Thi Thanh , Yurchenko Ekaterina A. , Yurchenko Anton N. , Berdyshev Dmitry V.
Published: May 2023

The metabolic profile of the Aspergillus sp. 1901NT-1.2.2 sponge-associated fungal strain was investigated using the HPLC MS technique, and more than 23 peaks in the HPLC MS chromatogram were detected. Only two minor peaks were identified as endocrocin and terpene derivative MS data from the GNPS database. The main compound was isolated and identified as known anthraquinone derivative vismione E. The absolute stereochemistry of vismione E was established for the first time using ECD and quantum chemical methods. Vismione E showed high cytotoxic activity against human breast cancer MCF-7 cells, with an IC50 of 9.0 µM, in comparison with low toxicity for normal human breast MCF-10A cells, with an IC50 of 65.3 µM. It was found that vismione E inhibits MCF-7 cell proliferation and arrests the cell cycle in the G1 phase. Moreover, the negative influence of vismione E on MCF-7 cell migration was detected. Molecular docking of vismione E suggested the IMPDH2 enzyme as one of the molecular targets for this anthraquinone derivative.
Role of cGAS–Sting Signaling in Alzheimer’s Disease
Authors: Govindarajulu Manoj , Ramesh Sindhu , Beasley McNeil , Lynn Graham , Wallace Caleigh , Labeau Sammie , Pathak Suhrud , Nadar Rishi , Moore Timothy , Dhanasekaran Muralikrishnan
Published: May 2023

There is mounting evidence that the development of Alzheimer’s disease (AD) interacts extensively with immunological processes in the brain and extends beyond the neuronal compartment. Accumulation of misfolded proteins can activate an innate immune response that releases inflammatory mediators and increases the severity and course of the disease. It is widely known that type-I interferon-driven neuroinflammation in the central nervous system (CNS) accelerates the development of numerous acute and chronic CNS diseases. It is becoming better understood how the cyclic GMP–AMP synthase (cGAS) and its adaptor protein Stimulator of Interferon Genes (STING) triggers type-I IFN-mediated neuroinflammation. We discuss the principal elements of the cGAS–STING signaling pathway and the mechanisms underlying the association between cGAS–STING activity and various AD pathologies. The current understanding of beneficial and harmful cGAS–STING activity in AD and the current treatment pathways being explored will be discussed in this review. The cGAS–STING regulation offers a novel therapeutic opportunity to modulate inflammation in the CNS because it is an upstream regulator of type-I IFNs
A Scoping Review Investigating the “Gene-Dosage Theory” of Mitochondrial DNA in the Healthy Skeletal Muscle
Authors: Pedersen Zandra Overgaard , Pedersen Britt Staevnsbo , Larsen Steen , Dysgaard Tina
Published: May 2023

This review provides an overview of the evidence regarding mtDNA and valid biomarkers for assessing mitochondrial adaptions. Mitochondria are small organelles that exist in almost all cells throughout the human body. As the only organelle, mitochondria contain their own DNA, mitochondrial DNA (mtDNA). mtDNA-encoded polypeptides are subunits of the enzyme complexes in the electron transport chain (ETC) that are responsible for production of ATP to the cells. mtDNA is frequently used as a biomarker for mitochondrial content, since changes in mitochondrial volume are thought to induce similar changes in mtDNA. However, some exercise studies have challenged this “gene-dosage theory”, and have indicated that changes in mitochondrial content can adapt without changes in mtDNA. Thus, the aim of this scoping review was to summarize the studies that used mtDNA as a biomarker for mitochondrial adaptions and address the question as to whether changes in mitochondrial content, induce changes in mtDNA in response to aerobic exercise in the healthy skeletal muscle. The literature was searched in PubMed and Embase. Eligibility criteria included: interventional study design, aerobic exercise, mtDNA measurements reported pre- and postintervention for the healthy skeletal muscle and English language. Overall, 1585 studies were identified. Nine studies were included for analysis. Eight out of the nine studies showed proof of increased oxidative capacity, six found improvements in mitochondrial volume, content and/or improved mitochondrial enzyme activity and seven studies did not find evidence of change in mtDNA copy number. In conclusion, the findings imply that mitochondrial adaptions, as a response to aerobic exercise, can occur without a change in mtDNA copy number.
Analysis of SARS-CoV-2 Spike Protein Variants with Recombinant Reporter Viruses Created from a Bacmid System
Authors: Cordsmeier Arne , Jungnickl Doris , Herrmann Alexandra , Korn Klaus , Ensser Armin
Published: May 2023

SARS-CoV-2, the causative agent of COVID-19, has spread around the world with more than 700 million cases and 6.8 million deaths. Various variants of concern (VoC) have emerged due to mutations and recombination and concurrent selection for increased viral fitness and immune evasion. The viral protein that primarily determines the pathogenicity, infectivity, and transmissibility is the Spike protein. To analyze the specific impact of variant Spike proteins on infection dynamics, we constructed SARS-CoV-2 with a uniform B.1 backbone but with alternative Spike proteins. In addition, ORF6 was replaced by EYFP as a biological safety measure, and for use of this well-established reporter. We show that namely the delta variant Spike proteins cause a distinct phenotype from the wild type (B.1, D614G) and other variants of concern. Furthermore, we demonstrate that the omicron BA.1 Spike results in lower viral loads and a less efficient spread in vitro. Finally, we utilized viruses with the two different reporters EYFP and mCherry to establish a competitive growth assay, demonstrating that most but not all Spike variant viruses were able to outcompete wild type SARS-CoV-2 B.1.
Dengue Virus Capsid Protein Facilitates Genome Compaction and Packaging
Authors: Boon Priscilla L. S. , Martins Ana S. , Lim Xin Ni , Enguita Francisco J. , Santos Nuno C. , Bond Peter J. , Wan Yue , Martins Ivo C. , Huber Roland G.
Published: May 2023

Dengue virus (DENV) is a single-stranded (+)-sense RNA virus that infects humans and mosquitoes, posing a significant health risk in tropical and subtropical regions. Mature virions are composed of an icosahedral shell of envelope (E) and membrane (M) proteins circumscribing a lipid bilayer, which in turn contains a complex of the approximately 11 kb genomic RNA with capsid (C) proteins. Whereas the structure of the envelope is clearly defined, the structure of the packaged genome in complex with C proteins remains elusive. Here, we investigated the interactions of C proteins with viral RNA, in solution and inside mature virions, via footprinting and cross-linking experiments. We demonstrated that C protein interaction with DENV genomes saturates at an RNA:C protein ratio below 1:250. Moreover, we also showed that the length of the RNA genome interaction sites varies, in a multimodal distribution, consistent with the C protein binding to each RNA site mostly in singlets or pairs (and, in some instances, higher numbers). We showed that interaction sites are preferentially sites with low base pairing, as previously measured by 2′-acetylation analyzed by primer extension (SHAPE) reactivity indicating structuredness. We found a clear association pattern emerged: RNA-C protein binding sites are strongly associated with long-range RNA–RNA interaction sites, particularly inside virions. This, in turn, explains the need for C protein in viral genome packaging: the protein has a chief role in coordinating these key interactions, promoting proper packaging of viral RNA. Such sites are, thus, highly consequential for viral assembly, and, as such, may be targeted in future drug development strategies against these and related viruses.
Phototoxic or Photoprotective?—Advances and Limitations of Titanium (IV) Oxide in Dermal Formulations—A Review
Authors: Gackowski Michał , Osmałek Tomasz , Froelich Anna , Otto Filip , Schneider Raphaël , Lulek Janina
Published: May 2023

The widespread role of titanium (IV) oxide (TiO2) in many industries makes this substance of broad scientific interest. TiO2 can act as both a photoprotector and photocatalyst, and the potential for its role in both applications increases when present in nanometer-sized crystals. Its sunlight-scattering properties are used extensively in sunscreens. Furthermore, attempts have been made to incorporate TiO2 into dermal formulations of photolabile drugs. However, the propensity to generate reactive oxygen species (ROS) rendering this material potentially cytotoxic limits its role. Therefore, modifications of TiO2 nanoparticles (e.g., its polymorphic form, size, shape, and surface modifications) are used in an effort to reduce its photocatalytic effects. This review provides an overview of the potential risks arising from and opportunities presented by the use of TiO2 in skin care formulations.
Involvement of Degenerating 21.5 kDa Isoform of Myelin Basic Protein in the Pathogenesis of the Relapse in Murine Relapsing–Remitting Experimental Autoimmune Encephalomyelitis and MS Autopsied Brain
Authors: Takano Chie , Takano Takuma , Masumura Makoto , Nakamura Ryuichi , Koda Shuichi , Bochimoto Hiroki , Yoshida Shigetaka , Bando Yoshio
Published: May 2023

Multiple sclerosis (MS) is the chronic inflammatory demyelinating disease of the CNS. Relapsing–remitting MS (RRMS) is the most common type of MS. However, the mechanisms of relapse and remission in MS have not been fully understood. While SJL mice immunized with proteolipid protein (PLP) develop relapsing–remitting experimental autoimmune encephalomyelitis (RR-EAE), we have recently observed that some of these mice were resistant to the active induction of relapsing EAE after initial clinical and histological symptoms of EAE with a severity similar to the relapsing EAE mice. To clarify the mechanism of relapsing, we examined myelin morphology during PLP139–151-induced RR-EAE in the SJL mice. While RR-EAE mice showed an increased EAE severity (relapse) with CNS inflammation, demyelination with abnormal myelin morphology in the spinal cord, the resistant mice exhibited a milder EAE phenotype with diminished relapse. Compared with the RR-EAE mice, the resistant mice showed less CNS inflammation, demyelination, and abnormalities of the myelin structure. In addition, scanning electron microscopic (SEM) analysis with the osmium-maceration method displayed ultrastructural abnormalities of the myelin structure in the white matter of the RR-EAE spinal cord, but not in that of the resistant mice. While the intensity of myelin staining was reduced in the relapsing EAE spinal cord, immunohistochemistry and immunoblot analysis revealed that the 21.5 kDa isoform of degenerating myelin basic protein (MBP) was specifically induced in the relapsing EAE spinal cord. Taken together, the neuroinflammation-induced degenerating 21 kDa isoform of MBP sheds light on the development of abnormal myelin on the relapse of MS pathogenesis.
Identification of Catechins’ Binding Sites in Monomeric Aβ42 through Ensemble Docking and MD Simulations
Authors: Firouzi Rohoullah , Sowlati-Hashjin Shahin , Chávez-García Cecilia , Ashouri Mitra , Karimi-Jafari Mohammad Hossein , Karttunen Mikko
Published: May 2023

The assembly of the amyloid-β peptide (Aβ) into toxic oligomers and fibrils is associated with Alzheimer’s disease and dementia. Therefore, disrupting amyloid assembly by direct targeting of the Aβ monomeric form with small molecules or antibodies is a promising therapeutic strategy. However, given the dynamic nature of Aβ, standard computational tools cannot be easily applied for high-throughput structure-based virtual screening in drug discovery projects. In the current study, we propose a computational pipeline—in the framework of the ensemble docking strategy—to identify catechins’ binding sites in monomeric Aβ42. It is shown that both hydrophobic aromatic interactions and hydrogen bonding are crucial for the binding of catechins to Aβ42. Additionally, it has been found that all the studied ligands, especially EGCG, can act as potent inhibitors against amyloid aggregation by blocking the central hydrophobic region of Aβ. Our findings are evaluated and confirmed with multi-microsecond MD simulations. Finally, it is suggested that our proposed pipeline, with low computational cost in comparison with MD simulations, is a suitable approach for the virtual screening of ligand libraries against Aβ.
Enhancing Traceability Link Recovery with Fine-Grained Query Expansion Analysis
Authors: Peng Tao , She Kun , Shen Yimin , Xu Xiangliang , Yu Yue
Published: May 2023

Requirement traceability links are an essential part of requirement management software and are a basic prerequisite for software artifact changes. The manual establishment of requirement traceability links is time-consuming. When faced with large projects, requirement managers spend a lot of time in establishing relationships from numerous requirements and codes. However, existing techniques for automatic requirement traceability link recovery are limited by the semantic disparity between natural language and programming language, resulting in many methods being less accurate. In this paper, we propose a fine-grained requirement-code traceability link recovery approach based on query expansion, which analyzes the semantic similarity between requirements and codes from a fine-grained perspective, and uses a query expansion technique to establish valid links that deviate from the query, so as to further improve the accuracy of traceability link recovery. Experiments showed that the approach proposed in this paper outperforms state-of-the-art unsupervised traceability link recovery methods, not only specifying the obvious advantages of fine-grained structure analysis for word embedding-based traceability link recovery, but also improving the accuracy of establishing requirement traceability links. The experimental results demonstrate the superiority of our approach.
Cardiovascular Mortality in 10 Cohorts of Middle-Aged Men Followed-Up 60 Years until Extinction: The Seven Countries Study
Authors: Menotti Alessandro , Puddu Paolo Emilio , Kafatos Anthony G. , Tolonen Hanna , Adachi Hisashi , Jacobs David R.
Published: May 2023

Objectives. To investigate mortalities from three major groups of cardiovascular diseases (CVDs) in a pooled cohort and followed up until extinction. Materials and Methods. Ten cohorts of men (N = 9063) initially aged 40–59, in six countries, were examined and followed-up for 60 years. The major CVD groups were coronary heart disease (CHD), cerebrovascular diseases (STROKE) and other heart diseases of uncertain etiology (HDUE). Results. Death rates from CHD were higher in countries with high serum cholesterol levels (USA, Finland and The Netherlands) and lower in countries with low cholesterol levels (Italy, Greece and Japan), but the opposite was observed for STROKE and HDUE, which became the most common CVD mortalities in all countries during the last 20 years of follow-up. Systolic blood pressure and smoking habits were, at an individual level, the common risk factors for the three groups of CVD conditions, while serum cholesterol level was the most common risk factor only for CHD. Overall, death rates for the pooled CVDs were 18% higher in North American and Northern European countries, while CHD rates were 57% higher in the same countries. Conclusions. Differences in lifelong CVD mortalities across different countries were smaller than expected due to the different rates of the three groups of CVD, and the indirect determinant of this seemed to be baseline serum cholesterol levels.
The Influence of Polishing and Artificial Aging on BioMed Amber® Resin’s Mechanical Properties
Authors: Paradowska-Stolarz Anna , Mikulewicz Marcin , Wieckiewicz Mieszko , Wezgowiec Joanna
Published: May 2023

Currently, 3D print is becoming more common in all branches of medicine, including dentistry. Some novel resins, such as BioMed Amber (Formlabs), are used and incorporated to more advanced techniques. The aims of the study were to check whether or not polishing and/or artificial aging influences the properties of the 3D-printed resin. A total of 240 specimens of BioMed Resin were printed. Two shapes (rectangular and dumbbell) were prepared. Of each shape, 120 specimens were divided into four groups each (with no influence, after polishing only, after artificial aging only, and after both polishing and artificial aging). Artificial aging took place in water at the temperature of 37 °C for 90 days. For testing, the universal testing machine (Z10-X700, AML Instruments, Lincoln, UK) was used. The axial compression was performed with the speed of 1mm/min. The tensile modulus was measured with the constant speed of 5 mm/min. The highest resistance to compression and tensile test were observed in the specimens that were neither polished nor aged (0.88 ± 0.03 and 2.88 ± 0.26, respectively). The lowest resistance to compression was observed in the specimens that were not polished, but aged (0.70 ± 0.02). The lowest results of the tensile test were observed when specimens were both polished and aged (2.05 ± 0.28). Both polishing and artificial aging weakened the mechanical properties of the BioMed Amber resin. The compressive modulus changed much with or without polishing. The tensile modulus differed in specimens that were either polished or aged. The application of both did not change the properties when compared to the polished or aged probes only.
Surfacing Positioning Point Prediction of Underwater Glider with a New Combination Model
Authors: Zhang Runfeng , Niu Wendong , Wan Xu , Wu Yining , Xue Dongyang , Yang Shaoqiong
Published: May 2023

Combination prediction models have gained great development in the area of information science, and are widely applied in engineering fields. The underwater glider (UG) is a new type of unmanned vehicle used in ocean observation for the advantages of long endurance, low noise, etc. However, due to its lower speed relative to the ocean current, the surfacing positioning point (SPP) of an UG often drifts greatly away from the preset waypoint. Therefore, this paper proposes a new combination model for predicting the SPP at different time scales. First, the kinematic model and working flow of the Petrel-L glider is analyzed. Then, this paper introduces the principles of a newly proposed combination model which integrates single prediction models with optimal weight. Afterwards, to make an accurate prediction, ocean current data are interpolated and averaged according to the diving depth of UGs as an external influencing factor. Meanwhile, with sea trial data collected in the northern South China Sea by Petrel-L, which had a total range of 4230.5 km, SPPs are predicted using single prediction models at different time scales, and the combination weights are derived with a novel simulated annealing optimized Frank–Wolfe method. Finally, the evaluated results demonstrate that the MAE and MSE are 966 m and 969 m, which proves that the single models achieved good performance under specified situations, and the combination model performed better at full scale because it integrates the advantages of the single models. Furthermore, the predicted SPPs will be helpful in the dead reckoning of the UG, and the proposed new combination method could extend into other fields for prediction.