bluuebunny/crossref_metadata_2025 huggingface dataset:
Intelligent and Secure Cloud–Edge Collaborative Industrial Information Encryption Strategy Based on Credibility Assessment
Authors: Tan Aiping , Dong Chenglong , Wang Yan , Wang Chang , Xia Changqing
Published: September 2024

As industries develop and informatization accelerates, enterprise collaboration is increasing. However, current architectures face malicious attacks, data tampering, privacy issues, and security and efficiency problems in information exchange and enterprise credibility. Additionally, the complexity of cyber threats requires integrating intelligent security measures to proactively defend against sophisticated attacks. To address these challenges, this paper introduces an intelligent and secure cloud–edge collaborative industrial information encryption strategy based on credibility assessment. The proposed strategy incorporates adaptive encryption specifically designed for cloud–edge and edge–edge architectures and utilizes attribute encryption to control access to user-downloaded data, ensuring secure information exchange. A mechanism for assessing enterprise credibility over a defined period helps maintain a trusted collaborative environment, crucial for identifying and mitigating risks from potentially malicious or unreliable entities. Furthermore, integrating intelligent threat detection and response systems enhances overall security by continuously monitoring and analyzing network traffic for anomalies. Experimental analysis evaluates the security of communication paths and examines how enterprise integrity influences collaboration outcomes. Simulation results show that this approach enhances enterprise integrity, reduces losses caused by harmful actors, and promotes efficient collaboration without compromising security. This intelligent and secure strategy not only safeguards sensitive data but also ensures the resilience and trustworthiness of the collaborative network.
Preservative Effect of a Gelatin-Based Film Including a Gelidium sp. Flour Extract on Refrigerated Atlantic Mackerel
Authors: López Lucía , Gómez Antonio , Trigo Marcos , Miranda José M. , Barros-Velázquez Jorge , Aubourg Santiago P.
Published: September 2024

This research evaluated the preservative properties of flour from the alga Gelidium sp., which is a waste substrate resulting from commercial phycocolloid extraction. Gelatin-based biofilms, which included two different concentrations of red alga flour, were developed and used as packaging systems during refrigerated storage (up to 9 days at 4 °C) of Atlantic mackerel (Scomber scombrus) muscle. In all batches tested, a progressive decrease in quality could be observed in the muscle of the fish as the storage time increased. Compared with the control fish, the Gelidium alga flour extract had an inhibitory effect (p < 0.05) on microbial activity (total aerobes, psychrotrophs, and proteolytic bacteria), lipid oxidation (peroxide, thiobarbituric acid, fluorescence and polyene indices), lipid hydrolysis (formation of free fatty acids) and pH increase in refrigerated mackerel muscle. In contrast, no significant effect (p > 0.05) was observed on trimethylamine formation, Enterobacteriaceae, or lipolytic bacteria counts. A preservative effect resulting from the incorporation of Gelidium alga flour into the gelatin-based biofilm was observed, indicating both quality and safety enhancement. In accordance with current global interest in the search for natural and waste sources, a novel and beneficial use of Gelidium flour for enhancing the quality of refrigerated fish has been proposed.
A Novel and Stable Benchmark for Breast Measurement
Authors: Zhao Yulin , Wu Chihua , Luh Dingbang , Feng Bingbing
Published: September 2024

Selecting an appropriate bra product has long been a challenge for adolescent girls, whose breasts are rapidly growing. This challenge arises due to the absence of a rational benchmark for breast measurement. Traditional benchmarks are based on ergonomic principles, using reference points located on the human skeleton. However, the breast lacks a bone structure for support, leading to highly variable measurement results. In this study, the jugular notch and the xiphoid process were selected as breast measurement points according to academic principles. Their accuracy, stability, and deviation were experimentally investigated through tactile assessment of adolescent girls at different stages of development. Based on the experimental results, a novel breast measurement coordinate system was established, and its accuracy was verified by conversion calculations using a geodetic coordinate system. The results indicated that the numerical calculation of the breast shape was more accurate using the newly established breast measurement coordinate system.
Dynamic Response Analysis of Asphalt Pavement under Pavement-Unevenness Excitation
Authors: Liu Heng , Liu Xiaoge , Wei Ankang , Cai Yingchun
Published: September 2024

This paper investigates and analyzes the dynamic response of asphalt pavement under pavement-unevenness excitation based on an orthogonal vector function system and efficient DVP (dual variable and position) method. Firstly, starting from the pavement unevenness of the vehicle excitation source, the pavement-unevenness excitation is established by using the filtered white-noise method, and the random load of the vehicle model is obtained by simulation. Then, based on the basic governing equation of the road-surface problem under the random load, the analytical solution of the road-surface mechanical response is obtained by using the orthogonal vector function system and DVP method. The effects of pavement-unevenness grade, vehicle speed, vehicle load, interlayer contact condition, and transverse isotropy on the mechanical response of the road surface are analyzed via the analytical results. The results show that DVP can effectively solve the dynamic response of pavements under the excitation of pavement unevenness; in addition, it can also be applied to certain situations, such as transverse isotropy of materials and interface conditions. The results show that the pavement unevenness does not affect the average stress and strain of each layer but has a significant effect on the peak value and dispersion degree. An increase in vehicle speed causes a peak in strain and a larger coefficient of variation. Poor bonding between interfaces can lead to increased stress and strain at the bottom of the surface layer.
Salix humboldtiana as an Indicator of Air Pollution by Trace Metals in the Urban Areas of the City of Loja, Southern Ecuador
Authors: Benítez Ángel , Ordóñez Diego , Calva James
Published: September 2024

Air pollution is the most important environmental problem in urban areas related to vehicular traffic and industrial activities. The widespread presence of common urban trees, such as Salix humboldtiana, and their ability to tolerate diverse environmental conditions make this species an especially promising candidate for assessing environmental metal contamination. Therefore, biomonitoring with vascular plants has been widely used to assess air pollution, especially the accumulation of trace metal concentrations. Therefore, for the first time, we analyzed the concentration of trace metals using Salix humboldtiana in twelve areas with different levels of pollution in a city in Southern Ecuador. For this purpose, samples were taken from each site to assess the accumulation of trace metals such as Zn, Mn, Fe, Cd, Cr, Pb, Cu, Al, and Ni. The results obtained showed significant differences in the concentrations of Zn, Mn, Fe, and Cd between the urban areas and the control area, indicating that the central areas were the most polluted by vehicular traffic. However, these findings suggest that Salix humboldtiana may not be a particularly effective tool for quantifying levels of environmental metal contamination such as Cu and Ni, at least in urban areas in the city of Loja. This study has demonstrated that Salix humboldtiana leaves can effectively monitor trace metals associated with road traffic emissions in areas with varying levels of vehicular activity, indicating that vascular plants can be utilized for this purpose in tropical cities.
Concurrent Particulate Matter and Heat Exposure in Working and Non-Working Women in Rural Guatemala
Authors: Butler-Dawson Jaime , Erlandson Grant , Jaramillo Diana , Calvimontes Laura , Pilloni Daniel , Seidel James , Castro Colton , Villarreal Hernandez Karely , Krisher Lyndsay , Brindley Stephen , Dally Miranda , Cruz Alex , James Katherine A. , Newman Lee S. , Schaeffer Joshua W. , Adgate John L.
Published: September 2024

High temperatures and air pollution exposure are individually known risks to human health, with amplifying adverse health effects during periods of co-exposure. This study compared co-occurring individual-level exposures to particulate matter (PM5, aerodynamic diameter of ≤5 μm) and heat among women in residential and agricultural settings in Guatemala. We measured personal and ambient exposure to PM5, temperature, and humidity among 21 female sugarcane workers in the fields and on their off days. We measured similar exposures among a group of 30 community members not involved in sugarcane work. We collected 171 personal PM5 measurements across 18 sampling days. The median workday personal PM5 concentration was 271 µg/m3, which was 3.6-fold higher than ambient area levels in the fields. The median personal PM5 concentration was 95.8 µg/m3 for off-work days and 83.5 µg/m3 for community days. The average workday individual-level temperature and humidity were 39.4 °C and 82.4%, respectively, with significantly lower temperatures on off-work and community days. The women workers and community members were exposed to high levels of PM5 and heat in both occupational and residential settings. Research needs to consider individual-level exposures at both work and home to help tailor more effective comprehensive prevention efforts to reduce risks.
Nonlinear Calibration and Temperature Sensitivity of Makrofol Solid-State Nuclear Track Detectors for Radon Measurement
Authors: Turtiainen Tuukka , Laine Jussi-Pekka , Rantanen Salla , Oinas Tiina
Published: September 2024

A key characteristic of a solid-state nuclear track detector (SSNTD) is that as more alpha tracks accumulate on the detector, the likelihood of track overlap will increase, making it difficult to distinguish individual events. This article presents the calibration of an in-house SSNTD using a Makrofol polycarbonate detector and electrochemical etching. The calibration employs a nonlinear log-logistic quantile function, which is nearly linear at low exposures but accounts for the reduced efficiency at high exposures due to overlapping alpha tracks. The function can be fitted to calibration measurements very accurately, eliminating systematic errors previously associated with the method at certain radon exposures. This article explores the uncertainties and detection limits associated with the calibration and outlines methods for their evaluation. Additionally, it includes a preliminary discussion on the method’s sensitivity to temperature.
An RBF Method for Time Fractional Jump-Diffusion Option Pricing Model under Temporal Graded Meshes
Authors: Gong Wenxiu , Xu Zuoliang , Sun Yesen
Published: September 2024

This paper explores a numerical method for European and American option pricing under time fractional jump-diffusion model in Caputo scene. The pricing problem for European options is formulated using a time fractional partial integro-differential equation, whereas the pricing of American options is described by a linear complementarity problem. For European option, we present nonuniform discretization along time and the radial basis function (RBF) method for spatial discretization. The stability and convergence analysis of the discrete scheme are carried out in the case of European options. For American option, the operator splitting method is adopted which split linear complementary problem into two simple equations. The numerical results confirm the accuracy of the proposed method.
New Properties and Matrix Representations on Higher-Order Generalized Fibonacci Quaternions with q-Integer Components
Authors: Kızılateş Can , Du Wei-Shih , Terzioğlu Nazlıhan , Chen Ren-Chuen
Published: September 2024

In this paper, by using q-integers and higher-order generalized Fibonacci numbers, we define the higher-order generalized Fibonacci quaternions with q-integer components. We give some special cases of these newly established quaternions. This article examines q-calculus and quaternions together. We obtain a Binet-like formula, some new identities, a generating function, a recurrence relation, an exponential generating function, and sum properties of quaternions with quantum integer coefficients. In addition, we obtain some new identities for these types of quaternions by using three new special matrices.
Quercus glauca Acorn Seed Coat Extract Promotes Wound Re-Epithelialization by Facilitating Fibroblast Migration and Inhibiting Dermal Inflammation
Authors: Kim Shin-Hye , Shin Hye-Lim , Son Tae Hyun , Lim So-An , Kim Dongsoo , Yoon Jun-Hyuck , Choi Hyunmo , Kim Hwan-Gyu , Choi Sik-Won
Published: September 2024

The skin, recognized as the largest organ in the human body, serves a vital function in safeguarding against external threats. Severe damage to the skin can pose significant risks to human health. There is an urgent requirement for safe and effective therapies for wound healing. While phytotherapy has been widely utilized for various health conditions, the potential of Quercus glauca in promoting wound healing has not been thoroughly explored. Q. glauca is a cultivated crop known for its abundance of bioactive compounds. This study examined the wound-healing properties of Quercus glauca acorn seed coat water extract (QGASE). The findings from the study suggest that QGASE promotes wound closure in HF cells by upregulating essential markers related to the wound-healing process. Additionally, QGASE demonstrates antioxidant effects, mitigating oxidative stress and aiding in recovery from injuries induced by H2O2. In vivo experiments provide additional substantiation supporting the efficacy of QGASE in enhancing wound healing. The collective results indicate that QGASE may be a promising candidate for the development of innovative therapeutic strategies aimed at enhancing skin wound repair.
Comprehensive Review and Assessment of Computational Methods for Prediction of N6-Methyladenosine Sites
Authors: Luo Zhengtao , Yu Liyi , Xu Zhaochun , Liu Kening , Gu Lichuan
Published: September 2024

N6-methyladenosine (m6A) plays a crucial regulatory role in the control of cellular functions and gene expression. Recent advances in sequencing techniques for transcriptome-wide m6A mapping have accelerated the accumulation of m6A site information at a single-nucleotide level, providing more high-confidence training data to develop computational approaches for m6A site prediction. However, it is still a major challenge to precisely predict m6A sites using in silico approaches. To advance the computational support for m6A site identification, here, we curated 13 up-to-date benchmark datasets from nine different species (i.e., H. sapiens, M. musculus, Rat, S. cerevisiae, Zebrafish, A. thaliana, Pig, Rhesus, and Chimpanzee). This will assist the research community in conducting an unbiased evaluation of alternative approaches and support future research on m6A modification. We revisited 52 computational approaches published since 2015 for m6A site identification, including 30 traditional machine learning-based, 14 deep learning-based, and 8 ensemble learning-based methods. We comprehensively reviewed these computational approaches in terms of their training datasets, calculated features, computational methodologies, performance evaluation strategy, and webserver/software usability. Using these benchmark datasets, we benchmarked nine predictors with available online websites or stand-alone software and assessed their prediction performance. We found that deep learning and traditional machine learning approaches generally outperformed scoring function-based approaches. In summary, the curated benchmark dataset repository and the systematic assessment in this study serve to inform the design and implementation of state-of-the-art computational approaches for m6A identification and facilitate more rigorous comparisons of new methods in the future.
Translating Lupus: Comparative Transcriptional Profiles of Preclinical Lupus Models and Their Relevance to Human Disease
Authors: Parker James T. , Chang Ching-Yun , Kersjes Kara , Higgins Ixavier A. , Vendel Andrew C. , Chang William Y.
Published: September 2024

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease which can present with mixed organ involvement. Kidney involvement in lupus nephritis (LN) is a severe complication and major cause of mortality in SLE patients, second only to cardiovascular disease. While mouse models have helped uncover some molecular pathways involved in SLE/LN, we need a better understanding of the connection of these pathways and the immune cells involved in disease pathogenesis to develop new and effective therapies. Furthermore, models used for studying SLE/LN in mice have a heterogeneous immune response and may not always represent disease manifestations observed in patients. Identifying models that have shared pathways with human disease would allow for better translation for developing effective SLE/LN therapies. The molecular pathways of five different SLE/LN models (MRL/lpr, poly (I:C)-induced, interferon-α-induced, bm12 GvHD, and spontaneous NZB/W F1) were compared to characterize the immune response in mouse kidneys. These models demonstrated varied magnitudes in immune responses and proportions of innate vs. adaptive cell involvement. These findings were compared to human molecular pathways and cell types from public databases, including the Accelerating Medicine Partnership–Systemic Lupus Erythematosus Program (AMP-SLE), to help corelate mechanisms involved in mouse models to human disease.
Harnessing the Power of Fermented Tea to Improve Gut Microbiota and Combat Obesity Epidemic
Authors: Zhang Ruyi , Li Qiling , Gu Yuxuan , Liao Wenli
Published: September 2024

The global rise in obesity rates has prompted a thorough evaluation of dietary strategies that may alleviate this metabolic issue. Fermented tea, a beverage rich in polyphenols and catechins, has emerged as a viable therapeutic option for obesity management. This review discusses the role of fermented tea in modulating the gut microbiome, a critical factor in energy regulation and obesity. We explore how the bioactive components in fermented tea influence gut health and their implications for metabolic health. Fermented tea may inhibit weight gain and fat accumulation in obese animal models, likely by promoting beneficial bacteria and suppressing harmful species. Changes in the production of short-chain fatty acids and improvements in gut barrier integrity are linked to enhanced insulin sensitivity and reduced inflammatory markers, essential for effective obesity management. However, barriers remain in applying these findings in clinical settings, such as the need for standardized fermentation techniques and accurate dosage assessments. This review underscores the therapeutic potential of fermented tea in obesity treatment and advocates for further research to enhance its integration with public health initiatives.
Changes in the Diet of an Invasive Predatory Crab, Chionoecetes opilio, in the Degrading Benthic Community of an Arctic Fjord
Authors: Kiselev Alexander D. , Zalota Anna K.
Published: September 2024

The introduction of a new species can lead to substantial changes in a new ecosystem. Local and introduced species’ survival depends on their ability to adapt to the new environment. Studying such adaptations is often hindered by multiple factors affecting the ecosystem. The introduction of a large predatory snow crab, Chionoecetes opilio, into the Kara Sea, is a unique invasive species affecting an otherwise undisturbed ecosystem. The crab has caused drastic changes in the macro- and megabenthic taxonomic structure, abundance, and biomass of the most common species in an Arctic fjord, Blagopoluchiya Bay. Stomach content and stable isotope analysis were applied to study crabs’ feeding habits. As the abundance of the most common prey items diminished, the crabs switched to other less accessible food. Prior to substantial changes in benthic communities, the diet of the snow crabs was similar to that of other invaded and native areas, where animal food predominates. However, with the degradation of the ecosystem, detritus contribution has substantially increased. The changes in prey items did not change the crab’s trophic status, and they continued to feed within the same trophic niche. In the depleted benthic communities of Blagopoluchiya Bay, the snow crab is forced to use all available food sources.
Effect of Pressure Loading on Heel Skin Temperature and Moisture in Healthy Volunteers: Preliminary Results
Authors: Carvalho Érica de , Marostica Leticia Costa , Trento Gabriela Fagundes , Marcolina Julia Scalco , Teló Fernanda Ceolin , Soares Rhea Silvia de Avila , Silveira Lidiana Batista Teixeira Dutra , Lima Suzinara Beatriz Soares de , Alves Paulo Jorge Pereira , Eberhardt Thaís Dresch
Published: September 2024

Recent studies emphasize the significance of skin microclimate in the prevention of pressure injuries (PI). The objective was to evaluate the effect of pressure loading on skin temperature and moisture in the heels of healthy adults. This is a before-and-after study performed at Brazil, in October 2022. Skin temperature (°C) was measured by an infrared digital thermometer, and skin moisture (%) using electrical bioimpedance. Ten individuals/twenty heels were evaluated. The average temperature of the right and left heel was the same at baseline (27.2 °C). It was recognized that after 30 min of pressure loading on the heels, there was a decrease in temperature, and after 15 min of pressure offloading, the temperature decreased again. It was found that at t0, the moisture of the right heel (12.6%) was lower than the left heel (15.6%). The median moisture in the right heel increased from t0 to t1 and decreased in t2, while in the left heel, there was a small variation of the median from t0 to t1, as well as to t2. The pressure loading leads to a decrease in temperature and changes the skin moisture of the heels of healthy individuals.
Single-Cell RNA Sequencing and Combinatorial Approaches for Understanding Heart Biology and Disease
Authors: Wang Le , Jin Bo
Published: September 2024

By directly measuring multiple molecular features in hundreds to millions of single cells, single-cell techniques allow for comprehensive characterization of the diversity of cells in the heart. These single-cell transcriptome and multi-omic studies are transforming our understanding of heart development and disease. Compared with single-dimensional inspections, the combination of transcriptomes with spatial dimensions and other omics can provide a comprehensive understanding of single-cell functions, microenvironment, dynamic processes, and their interrelationships. In this review, we will introduce the latest advances in cardiac health and disease at single-cell resolution; single-cell detection methods that can be used for transcriptome, genome, epigenome, and proteome analysis; single-cell multi-omics; as well as their future application prospects.
Identification of Candidate Genes for Cold Tolerance at Seedling Stage by GWAS in Rice (Oryza sativa L.)
Authors: Shi Huimin , Zhang Wenyu , Cao Huimin , Zhai Laiyuan , Song Qingxin , Xu Jianlong
Published: September 2024

Due to global climate change, cold temperatures have significantly impacted rice production, resulting in reduced yield and quality. In this study, we investigated two traits related to the cold tolerance (CT) of 1992 diverse rice accessions at the seedling stage. Geng accessions exhibited higher levels of CT compared to xian accessions, with the GJ-tmp subgroup displaying the strongest CT. However, extreme CT accessions were also identified within the xian subspecies. Through GWAS analysis based on the survival rate (SR) and leaf score of cold tolerance (SCT), a total of 29 QTLs associated with CT at the seedling stage were identified, among which four QTLs (qSR3.1a, qSR4.1a, qSR11.1x, and qSR12.1a) were found to be important. Furthermore, five candidate genes (LOC_Os03g44760, LOC_Os04g06900, LOC_Os04g07260, LOC_Os11g40610, and LOC_Os12g10710) along with their favorable haplotypes were identified through gene function annotation and haplotype analysis. Pyramiding multiple favorable haplotypes resulted in a significant improvement in CT performance. Subsequently, three selected accessions (CX534, B236, and IRIS_313-8565), carrying different superior alleles for CT, were selected and recommended for molecular breeding for CT using marker-assisted selection (MAS). The findings from this study provide valuable resources for enhancing rice’s ability for CT while laying a foundation for the future cloning of novel genes involved in conferring CT.
Dipsacoside B Attenuates Atherosclerosis by Promoting Autophagy to Inhibit Macrophage Lipid Accumulation
Authors: Quan Wenjuan , Sun Taoli , Hu Bo , Luo Quanye , Zhong Yancheng , Chen Wen , Tuo Qinhui
Published: September 2024

Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation and foam cell formation in the arterial wall. Promoting macrophage autophagy has emerged as a promising therapeutic strategy against atherosclerosis. Dipsacoside B (DB) is an oleanane-type pentacyclic triterpenoid saponin extracted from Lonicerae flos with potential anti-atherosclerotic properties. In this study, we investigated the effects of DB on atherosclerosis progression in ApoE−/− mice fed a high-fat diet and explored the underlying mechanisms in oxidized low-density lipoprotein (ox-LDL)-induced foam cells. DB treatment significantly reduced atherosclerotic lesion size, improved plaque stability, and regulated lipid metabolism without impairing liver and kidney function in ApoE−/− mice. In vitro studies revealed that DB dose-dependently inhibited ox-LDL internalization and intracellular lipid accumulation in RAW264.7 macrophages. Mechanistically, DB induced autophagy, as evidenced by increased autophagosome formation and upregulated expression of autophagy markers LC3-II and p62 both in vivo and in vitro. Inhibition of autophagy by chloroquine abolished the antiatherosclerotic and pro-autophagic effects of DB. Furthermore, DB treatment increased LC3-II and p62 mRNA levels, suggesting transcriptional regulation of autophagy. Collectively, our findings demonstrate that DB exerts anti-atherosclerotic effects by inhibiting foam cell formation via autophagy induction, providing new insights into the pharmacological actions of DB and its potential as a therapeutic agent against atherosclerosis.
Boosting Serotonin Synthesis Is Not Sufficient to Improve Motor Coordination of Mecp2 Heterozygous Mouse Model of Rett Syndrome
Authors: Villani Claudia , Sacchetti Giuseppina , Invernizzi Roberto W.
Published: September 2024

Motor deficit is a core symptom of Rett syndrome, a rare neurological disease caused in most cases by mutations of the methyl-CpG-binding protein2 (MECP2) gene. Serotonin reuptake inhibitors improve motor coordination in Mecp2 heterozygous (Het) mice and serotonin depletion prevented this effect. Here, we assess alterations in indole levels in various brain regions and whether boosting brain serotonin synthesis with the serotonin precursors tryptophan, 5-hydroxytryptophan and α-lactalbumin rescued motor coordination deficit of Mecp2 Het mice. Motor coordination was assessed in the accelerated rotarod during and after systemic administration of serotonin precursors for 2–3 weeks. Since no data are available, the effect of α-lactalbumin on tryptophan, serotonin and 5-hydroxyindoleacetic acid levels was evaluated in various brain regions in order to identify the dose of ALAC to evaluate on motor coordination. As compared to WT, Mecp2 Het mice show reduced levels of serotonin in the whole brain, hippocampus, brainstem and cerebral cortex, but not the striatum. Reduced levels of 5-hydroxyindoleacetic acid were observed in the hippocampus and brainstem. Doses of serotonin precursors increasing brain tryptophan and/or serotonin production and metabolism had no effect on motor coordination. The results indicate that boosting serotonin synthesis is not sufficient to improve motor coordination of Mecp2 Het mice.
Human Coronavirus 229E Uses Clathrin-Mediated Endocytosis as a Route of Entry in Huh-7 Cells
Authors: Andreu Sabina , Ripa Inés , López-Guerrero José Antonio , Bello-Morales Raquel
Published: September 2024

Human coronavirus 229E (HCoV-229E) is an endemic coronavirus responsible for approximately one-third of “common cold” cases. To infect target cells, HCoV-229E first binds to its receptor on the cell surface and then can follow different pathways, entering by direct fusion or by taking advantage of host cell mechanisms such as endocytosis. Based on the role of clathrin, the process can be classified into clathrin-dependent or -independent endocytosis. This study characterizes the role of clathrin-mediated endocytosis (CME) in HCoV-229E infection of the human hepatoma cell line Huh-7. Using specific CME inhibitory drugs, we demonstrated that blocking CME significantly reduces HCoV-229E infection. Additionally, CRISPR/Cas9-mediated knockout of the µ subunit of adaptor protein complex 2 (AP-2) further corroborated the role of CME, as KOs showed over a 50% reduction in viral infection. AP-2 plays an important role in clathrin recruitment and the maturation of clathrin-coated vesicles. Our study also confirmed that in Huh-7 cells, HCoV-229E requires endosomal acidification for successful entry, as viral entry decreased when treated with lysomotropic agents. Furthermore, the colocalization of HCoV-229E with early endosome antigen 1 (EEA-1), only present in early endosomes, suggested that the virus uses an endosomal route for entry. These findings highlight, for the first time, the role of CME in HCoV-229E infection and confirm previous data of the use of the endosomal route at a low pH in the experimental cell model Huh-7. Our results provide new insights into the mechanisms of entry of HCoV-229E and provide a new basis for the development of targeted antiviral therapies.
Repurposing Nitazoxanide for Potential Treatment of Rare Disease Lymphangioleiomyomatosis
Authors: Bähr Stella , Rue Ryan W. , Smith Carly J. , Evans Jillian F. , Köster Hubert , Krymskaya Vera P. , Pleimes Dirk
Published: September 2024

Lymphangioleiomyomatosis (LAM) is a rare genetic lung disease. Unfortunately, treatment with the mTORC1 inhibitor Rapamycin only slows disease progression, and incomplete responses are common. Thus, there remains an urgent need to identify new targets for the development of curative LAM treatments. Nitazoxanide (NTZ) is an orally bioavailable antiprotozoal small molecule drug approved for the treatment of diarrhea caused by Giardia lamblia or Cryptosporidium parvum in children and adults, with a demonstrated mTORC1 inhibitory effect in several human cell lines. NTZ’s excellent safety profile characterized by its more than 20 years of clinical use makes it a promising candidate for repurposing. Our rationale for this study was to further investigate NTZ’s effect using in vitro and in vivo LAM models and to elucidate the underlying molecular mechanism beyond mTORC1 inhibition. For this purpose, we investigated cell proliferation, cell viability, and changes in protein phosphorylation and expression in primary human cell cultures derived from LAM lung samples before translating our results into a syngeneic mouse model utilizing Tsc2-null cells. NTZ reduced cell growth for all tested cell lines at a dose of about 30 µM. Lower doses than that had no effect on cell viability, but doses above 45 µM lowered the viability by about 10 to 15% compared to control. Interestingly, our western blot revealed no inhibition of mTORC1 and only a mild effect on active ß-Catenin. Instead, NTZ had a pronounced effect on reducing pAkt. In the mouse model, prophylactic NTZ treatment via the intraperitoneal and oral routes had some effects on reducing lung lesions and improving body weight retention, but the results remain inconclusive.
Placental Tissue Calcification and Its Molecular Pathways in Female Patients with Late-Onset Preeclampsia
Authors: Ortega Miguel A. , Pekarek Tatiana , De Leon-Oliva Diego , Boaru Diego Liviu , Fraile-Martinez Oscar , García-Montero Cielo , Bujan Julia , Pekarek Leonel , Barrena-Blázquez Silvestra , Gragera Raquel , Rodríguez-Benitez Patrocinio , Hernández-Fernández Mauricio , López-González Laura , Díaz-Pedrero Raul , Asúnsolo Ángel , Álvarez-Mon Melchor , García-Honduvilla Natalio , Saez Miguel A. , De León-Luis Juan A. , Bravo Coral
Published: September 2024

Preeclampsia (PE) is a complex multisystem disease characterized by hypertension of sudden onset (>20 weeks’ gestation) coupled with the presence of at least one additional complication, such as proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. Hypertensive states during pregnancy carry life-threatening risks for both mother and baby. The pathogenesis of PE develops due to a dysfunctional placenta with aberrant architecture that releases factors contributing to endothelial dysfunction, an antiangiogenic state, increased oxidative stress, and maternal inflammatory responses. Previous studies have shown a correlation between grade 3 placental calcifications and an elevated risk of developing PE at term. However, little is known about the molecular pathways leading to placental calcification. In this work, we studied the gene and protein expression of c-Jun N-terminal kinase (JNK), Runt-related transcription factor 2 (RUNX2), osteocalcin (OSC), osteopontin (OSP), pigment epithelium-derived factor (PEDF), MSX-2/HOX8, SOX-9, WNT-1, and β-catenin in placental tissue from women with late-onset PE (LO-PE). In addition, we employed von Kossa staining to detect mineral deposits in placental tissues. Our results show a significant increase of all these components in placentas from women with LO-PE. Therefore, our study suggests that LO-PE may be associated with the activation of molecular pathways of placental calcification. These results could be the starting point for future research to describe the molecular mechanisms that promote placental calcification in PE and the development of therapeutic strategies directed against it.
Microscale Flow Control and Droplet Generation Using Arduino-Based Pneumatically-Controlled Microfluidic Device
Authors: Park Woohyun , Choe Se-woon , Kim Minseok
Published: September 2024

Microfluidics are crucial for managing small-volume analytical solutions for various applications, such as disease diagnostics, drug efficacy testing, chemical analysis, and water quality monitoring. The precise control of flow control devices can generate diverse flow patterns using pneumatic control with solenoid valves and a microcontroller. This system enables the active modulation of the pneumatic pressure through Arduino programming of the solenoid valves connected to the pressure source. Additionally, the incorporation of solenoid valve sets allows for multichannel control, enabling simultaneous creation and manipulation of various microflows at a low cost. The proposed microfluidic flow controller facilitates accurate flow regulation, especially through periodic flow modulation beneficial for droplet generation and continuous production of microdroplets of different sizes. Overall, we expect the proposed microfluidic flow controller to drive innovative advancements in technology and medicine owing to its engineering precision and versatility.
Aptamer-Mediated Electrochemical Detection of SARS-CoV-2 Nucleocapsid Protein in Saliva
Authors: Siu Ryan H. P. , Jesky Robert G. , Fan Yu-Jing , Au-Yeung Cyrus C. H. , Kinghorn Andrew B. , Chan Kwok-Hung , Hung Ivan Fan-Ngai , Tanner Julian A.
Published: September 2024

Gold standard detection of SARS-CoV-2 by reverse transcription quantitative PCR (RT-qPCR) can achieve ultrasensitive viral detection down to a few RNA copies per sample. Yet, the lengthy detection and labor-intensive protocol limit its effectiveness in community screening. In view of this, a structural switching electrochemical aptamer-based biosensor (E-AB) targeting the SARS-CoV-2 nucleocapsid (N) protein was developed. Four N protein-targeting aptamers were characterized on an electrochemical cell configuration using square wave voltammetry (SWV). The sensor was investigated in an artificial saliva matrix optimizing the aptamer anchoring orientation, SWV interrogation frequency, and target incubation time. Rapid detection of the N protein was achieved within 5 min at a low nanomolar limit of detection (LOD) with high specificity. Specific N protein detection was also achieved in simulated positive saliva samples, demonstrating its feasibility for saliva-based rapid diagnosis. Further research will incorporate novel signal amplification strategies to improve sensitivity for early diagnosis.
Role of the Dorsal Raphe Nucleus in Pain Processing
Authors: Zhang Huijie , Li Lei , Zhang Xujie , Ru Guanqi , Zang Weidong
Published: September 2024

The dorsal raphe nucleus (DRN) has gained attention owing to its involvement in various physiological functions, such as sleep–awake, feeding, and emotion, with its analgesic role being particularly significant. It is described as the “pain inhibitory nucleus” in the brain. The DRN has diverse projections from hypothalamus, midbrain, and pons. In turn, the DRN is a major source of projections to diverse cortex, limbic forebrain thalamus, and the midbrain and contains highly heterogeneous neuronal subtypes. The activation of DRN neurons in mice prevents the establishment of neuropathic, chronic pain symptoms. Chemogenetic or optogenetic inhibition neurons in the DRN are sufficient to establish pain phenotypes, including long-lasting tactile allodynia, that scale with the extent of stimulation, thereby promoting nociplastic pain. Recent progress has been made in identifying the neural circuits and cellular mechanisms in the DRN that are responsible for sensory modulation. However, there is still a lack of comprehensive review addressing the specific neuron types in the DRN involved in pain modulation. This review summarizes the function of specific cell types within DRN in the pain regulation, and aims to improve understanding of the mechanisms underlying pain regulation in the DRN, ultimately offering insights for further exploration.
Intravenous Thrombolysis with Urokinase for Acute Ischemic Stroke
Authors: Qiao Yue , Wang Jing , Nguyen Thanh , Liu Lan , Ji Xunming , Zhao Wenbo
Published: September 2024

Background: Intravenous thrombolysis is one of the most effective therapies for the treatment of acute ischemic stroke (AIS), with urokinase offering a cost-effective alternative to newer agents like alteplase and tenecteplase, especially in resource-limited settings. Methods: This review provides a comprehensive overview of the application of intravenous thrombolysis with urokinase for AIS in the clinical practice of stroke management, including the efficacy, safety, and cost-effectiveness of urokinase compared to other thrombolytic agents. Results: Urokinase, a first-generation thrombolytic drug, is a non-specific plasminogen activator that offers a cost-effective alternative. It has been used in clinical practice for over two decades to improve neurological outcomes in patients with AIS if administered within 6 h of ictus. Numerous studies have indicated that urokinase remains a viable option for patients who cannot access alteplase or tenecteplase because of economic constraints, time window limitations, availability, or other reasons. Conclusions: In low- and middle-income countries, urokinase is a cost-effective alternative thrombolytic drug. High-level evidence-based medical research is therefore urgently needed to confirm that urokinase is not inferior to new-generation thrombolytic drugs, and to assess whether it may even be superior in some patient populations.
Acute Levodopa Challenge in Atypical Parkinsonism: Comprehensive Analysis of Individual Motor Responses
Authors: Ye Lan , Sani Sam Sadeghi , Veith Sanches Linda , Krey Lea Farina Magdalena , Wegner Florian , Höllerhage Matthias , Schrader Christoph , Höglinger Günter , Klietz Martin
Published: September 2024

The acute levodopa challenge is widely used to distinguish Parkinson’s disease (PD) from atypical parkinsonian syndromes (APSs) such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). In APSs, very few patients present a clinically relevant response to levodopa. The aim of this study was to determine whether patients with atypical parkinsonism benefit from levodopa in any aspect of their multiple motor deficits despite the generally poor response. This retrospective study analyzed individual motor responses to the acute levodopa challenge using the MDS-UPDRS III in 47 PSP, 26 MSA, and 71 PD patients at Hannover Medical School. Despite the generally poor levodopa response in both PSP and MSA patients, bradykinesia and rigidity were the symptoms most notably affected by levodopa in PSP patients, while MSA patients experienced significant improvements in bradykinesia and action tremor. These findings underscore the variability in levodopa response among PSP and MSA patients and highlight the need for personalized treatment approaches in atypical parkinsonism.
Estimated Disease Progression Trajectory of White Matter Disruption in Unilateral Temporal Lobe Epilepsy: A Data-Driven Machine Learning Approach
Authors: Sone Daichi , Sato Noriko , Shigemoto Yoko , Beheshti Iman , Kimura Yukio , Matsuda Hiroshi
Published: September 2024

Background/Objectives: Although the involvement of progressive brain alterations in epilepsy was recently suggested, individual patients’ trajectories of white matter (WM) disruption are not known. Methods: We investigated the disease progression patterns of WM damage and its associations with clinical metrics. We examined the cross-sectional diffusion tensor imaging (DTI) data of 155 patients with unilateral temporal lobe epilepsy (TLE) and 270 age/gender-matched healthy controls, and we then calculated the average fractional anisotropy (FA) values within 20 WM tracts of the whole brain. We used the Subtype and Stage Inference (SuStaIn) program to detect the progression trajectory of FA changes and investigated its association with clinical parameters including onset age, disease duration, drug-responsiveness, and the number of anti-seizure medications (ASMs). Results: The SuStaIn algorithm identified a single subtype model in which the initial damage occurs in the ipsilateral uncinate fasciculus (UF), followed by damage in the forceps, superior longitudinal fasciculus (SLF), and anterior thalamic radiation (ATR). This pattern was replicated when analyzing TLE with hippocampal sclerosis (n = 50) and TLE with no lesions (n = 105) separately. Further-progressed stages were associated with longer disease duration (p < 0.001) and a greater number of ASMs (p = 0.001). Conclusions: the disease progression model based on WM tracts may be useful as a novel individual-level biomarker.
Contrast Sensitivity Is Impaired in Suspected Primary Open-Angle Glaucoma Patients
Authors: Tripolone María Constanza , Issolio Luis Alberto , Perez Daniel Osvaldo , Barrionuevo Pablo Alejandro
Published: September 2024

Purpose: To assess spatial contrast sensitivity (CS) in suspected primary open-angle glaucoma (POAG) patients. Methods: CS was measured using sinusoidal gratings of 4 cycles/degree. First, foveal and peripheral CS were assessed in 34 suspected POAG patients and compared with 71 and 28 age-matched healthy individuals for foveal and peripheral conditions, respectively. Second, foveal CS was assessed in 34 early POAG patients age-matched with suspected POAG patients. Analyses were performed considering two age ranges: Under and Over 50 y.o. Correlations were evaluated between CS and clinical parameters. Diagnostic accuracy was also analyzed. Results: Peripheral CS was lower in older suspected POAG patients (23.4 ± 16.1) than the control group (39.1 ± 28.2) (p = 0.040). Foveal CS was reduced in suspected POAG participants (Under 50: 146.8 ± 63.3; p = 0.004. Over 50: 110.5 ± 65.0; p = 0.044) and in early POAG patients (Under 50: 141.2 ± 72.6; p = 0.002. Over 50: 80.2 ± 54.5 p < 0.001), both compared to the control group (Under 50: 213.5 ± 66.2. Over 50: 138.6 ± 71.7). CS was lower in early POAG than in POAG suspected in older patients (p = 0.042). Foveal CS was correlated with age (Early: p = 0.001. Suspect: p = 0.002) and with the cup–disc ratio only in early POAG patients (p < 0.001). Foveal CS had fair (AUC = 0.74) diagnostic accuracy for early POAG patients. Conclusions: CS in suspected POAG patients is lower than in healthy individuals. Our findings evidence the spatial vision loss before the onset of POAG.
Tentative Causes of Brain and Neuropsychological Alterations in Women Victims of Intimate Partner Violence
Authors: Daugherty Julia C. , García-Navas-Menchero Maripaz , Fernández-Fillol Carmen , Hidalgo-Ruzzante Natalia , Pérez-García Miguel
Published: September 2024

Victims of Intimate Partner Violence Against Women (IPVAW) experience neuropsychological and cerebral changes, which have been linked to several tentative causal mechanisms, including elevated cortisol levels, psychopathological disorders, traumatic brain injury (TBI), hypoxic/ischemic brain damage, and medical conditions related to IPVAW. While these mechanisms and their effects on brain function and neuropsychological health are well-documented in other clinical populations, they manifest with unique characteristics in women affected by IPVAW. Specifically, IPVAW is chronic and repeated in nature, and mechanisms are often cumulative and may interact with other comorbid conditions. Thus, in light of existing literature on neuropsychological alterations in other populations, and recognizing the distinct features in women who experience IPVAW, we propose a new theoretical model—the Neuro-IPVAW model. This framework aims to explain the complex interplay between these mechanisms and their impact on cognitive and brain health in IPVAW victims. We anticipate that this theoretical model will be valuable for enhancing our understanding of neuropsychological and brain changes related to intimate partner violence, identifying research gaps in these mechanisms, and guiding future research directions in this area.