bluuebunny/crossref_metadata_2025 huggingface dataset:
Shock action of super-short light pulse on magnetization precession in magnetoelastic system
Authors:   Syktyvkar Forest Institute, 167982, Russia, Syktyvkar, st. Lenina, 39, Asadullin F.F. , Pleshev D.A. ,   Syktyvkar Forest Institute, 167982, Russia, Syktyvkar, st. Lenina, 39, Shavrov V.G. ,   Institute of Radio Engineering and Electronics RAS, 125009, Russia, Moscow, st. Mokhovaya, 11 b.7, Shcheglov V.I. ,   Institute of Radio Engineering and Electronics RAS, 125009, Russia, Moscow, st. Mokhovaya, 11 b.7
Published: November 2024

The task about interaction of super-short light pulse on magnetoelastic system which has precession motion of magnetization is investigated. As a main mechanism it is investigated the decreasing of magnetization with power light action on spin system. It is investigated the development of magnetization precession by the action of light pulse. It is found that during the pulse action the amplitude vibrations is decreased and its frequency is increased. It is investigated the precession development in different meanings of light power. It is established the multi-regime character of magnetization vibrations by small pulse duration which is the same order as signal excitation period. It is established three regimes: regime №1 – stabile vibrations, regime №2 – the destroy of stabilization, regime №3 – shock excitation. It is established that the main distinguishing of regime №3 from first two regimes is the sharp jump increasing of amplitude as magnetic so the elastic vibrations which take pulse as a result of pulse action. It is found that as a result of high power long duration pulse it is arising the regime of in-flatness magnetic component stabilization. It is found that the main role in formation of this regime plays the magnetoelastic interaction.
Кольцевая гниль (Clavibacter sepedonicus) картофеля — опасность для картофелеводства в РФ и других странах ЕАЭС
Authors: Ерохова Мария Дмитриевна , Кузнецова Мария Алексеевна
Published: November 2024

Кольцевая гниль (возб. Clavibacter sepedonicus) считается одним из опаснейших заболеваний картофеля во многих европейских странах из-за выбраковки семенных клубней при сертификации семенного картофеля. В ряде европейских странах вредный организм имеет статус регулируемых карантинных организмов (в ЕС входит в Перечень А2). До недавнего времени C. sepedonicus входил в Перечень регулируемых некарантинных вредных организмов РФ. Бактерия является грамположительной фитопатогенной, поражающей картофель. Основными источниками инфекции являются заражённые клубни, кроме того, фитопатоген может сохраняться долгое время в виде биопленок на поверхностях в хранилище, на оборудовании и на контейнерах для транспортировки. Его широкое распространение может снижать экспортный потенциал отечественного картофеля и делает отечественный семенной картофель менее привлекательным для экспорта, а также приводит к значительным денежным потерям при понижении в категории в рамках национальной сертификации семенного картофеля. Для борьбы с семенной бактериальной инфекцией в первую очередь рекомендуется выращивание сертифицированного семенного картофеля, в котором официально подтверждено отсутствие вредного организма. Также необходимо осуществлять мероприятия по борьбе с «волонтёрными» растениями картофеля и дезинфцировать хранилища, тару, оборудование и др.
Adjusting the Balance between Alpha and Beta Risks in NN Classifiers
Authors: Thomas Philippe , Suhner Marie-Christine , Bril El Haouzi Hind
Published: November 2024

This paper delves into classification tasks, where data is categorized into binary classes, such as fraudulent/non-fraudulent or sick/not sick as example. Employing a statistical approach, this task entails utilizing hypothesis testing. Tuning this test involves selecting an acceptable risk alpha (associated with false positives), thereby implicating a beta risk (related to false negatives). In classification challenges, the principal aim is to mitigate the misclassification rate. However, the determination of these two risks is not be discretionary but rather enforced by the learning process, particularly evident when employing neural networks. This paper seeks to propose a modification of the learning algorithm for multilayer perceptron aimed at effectively balancing these risks. This adaptation hinges on leveraging a weighted criterion to minimize errors, accounting for the signs of different error types. This methodology is assessed across two benchmarks: a simulated dataset and a genuine medical dataset.

Keywords: neural network, multilayer perceptron, learning, classification, hypothesis test
Uncertainty Analysis in Ecological Risk Assessment: Sensitivity Analysis of Different Exposure Models
Authors: Bovitz Paul
Published: November 2024

Ecological risk assessments are used for decision making regarding releasing new products to market as well as remedial action required to address contamination at legacy sites. Uncertainty analysis is considered a key part of the process (USEPA 1997) but assessments seldom address uncertainty quantitatively. Key sources of uncertainty include: Sampling and analytical variability (soil/ sediment matrix, lab error), Choice of “Indicator” Species as Target Receptors for Different Exposure Pathways, Sample size. Bioaccumulation and Food Chain Modeling involve assumptions and uncertainty including: Linear assumption of bioaccumulation and selection of bioaccumulation factors; Other model inputs such as: Home range size, Dietary percentages, Body Weights, Ingestion Rate; Literature data on effects, Use of No Observed Adverse Effects Level (NOAEL) or Lowest Observed Adverse Effects Level (LOAEL) as a decision point. Toxicity testing where employed brings its own set of assumptions and interpretation that are subject to uncertainty. These include: Use of single organism, Correlation (or lack thereof) with Contaminants of Concern, Contaminant mixtures, and Reference area selection.
Keywords: Ecotoxicology, Risk Assessment, Ecology
Rankings of Shorelines of Georgian Black Sea Sector According to the Ecological Sensitivity Index (ESI)
Authors: Gelashvili Nino , Machitadze Nino , Gvakharia Vakhtang , Maisuradze Guram , Beridze Giorgi
Published: November 2024

Georgia is concidered as one of the best alternative transit countries connecting Asia and Europe. The transportation of oil and oil products from the Caspian and Central Asian regions to European countries is especially significant. This boosts the country’s economy, but it also increases the risk of marine environment pollution from oil hydrocarbons. In response to the risk of oil hydrocarbon pollution, it is necessary to intensify preventive monitoring efforts. This includes assessing the extent of oil hydrocarbon contamination on shores, in coastal waters, and in bottom sediments, as well as identifying and classifying areas along the coastline that are most sensitive to pollution. The division of shorelines into sensitive areas is carried out according to the ecological sensitivity index ESI, wich contains a numeric or alpha-numeric coded description of the shoreline characteristics for each shoreline segment. According to the 10 levels of sesitivity against oil pollution, the shoreline segments are classified from "low" sensitivity ESI 1 to "very high" sensitivity ESI 10, respectively 10 main classes and up to 30 sub-classes are identified. In Georgia coastal area, for the 113 km section from Ganmukhuri to Sarpi, we have identified shoreline segments with 7 main classes and 9 sub-classes of sensitivity.
Keywords: Black sea, Georgia, oil, sensitivity, rankings , pollution
Bataille, Lascaux y la degradación artística del neolítico
Authors: Bisignano Ignacio
Published: November 2024

Este escrito tiene el objetivo de otorgar claridad y contundencia a los enigmáticos dichos de Georges Bataille sobre el arte paleolítico de Lascaux que desarrolla en su libro Lascaux o el nacimiento del arte (2011). No resulta tan sencillo asimilar las apreciaciones de Bataille sobre Lascaux, ya que denomina esta creación prehistórica como un hecho “milagroso” y excepcional que habilita una “verdad” determinante sobre la condición humana. Dejando de lado la idea de que Bataille sostiene especulaciones metafísicas sin demasiado rigor epistémico y apoyando la tesis de que al leer detenidamente los dichos de este autor puede reconstruirse una idea sólida, coherente y racional sobre su pensamiento respecto al arte, mantengo la siguiente hipótesis: en Lascaux se cristaliza un vínculo íntimo e indisociable entre lo artístico y la historia, ya que lo que allí está en juego es en realidad la muestra explícita de una concepción desafiante frente a la historiografía tradicional. Este carácter rupturista del arte hace que Bataille deposite allí un tipo de conocimiento singular inaprensible desde la lógica proposicional, positiva o acumulativa que se desarrolla a partir de la revolución neolítica. Para esta tarea, tendré en cuenta las visiones sobre la historia que sostienen autores como Georges Didi-Huberman (2006), Walter Benjamin (2008) y Michel De Certeau (2007), los cuales desde su posición crítica sobre el conocimiento historiográfico contribuyen a esclarecer la enigmática posición de Bataille con respecto al tema.
Democracia, estética y libertad en la filosofía práctica de Juliane Rebentisch: tentativas desde el pensamiento de lo político
Authors: Cristobo Matías
Published: November 2024

La tradición de la Teoría Crítica ligada al Instituto de Investigación Social de Frankfurt ha sido frecuentemente periodizada teniendo en cuenta las sucesivas generaciones de pensadores que la animaron. Desde este recorte temporal, la llamada “tercera generación” de la Teoría Crítica renovó sus principales líneas de investigación incorporando a la tradición alemana de pensamiento los desarrollos del posfundacionalismo francés. En esta misma línea, una representante de la cuarta generación, Juliane Rebentisch (2024; 2013), encuentra en las teorías de Claude Lefort (1990; 1985), Jacques Rancière (2007; 2006) y Jacques Derrida (2011; 2005), nuevas formas de abordar problemas propios del idealismo alemán, tales como la apariencia estética, en su vínculo siempre conflictivo con la política democrática. Proponemos como objetivo de nuestro trabajo poner de manifiesto tanto la tesis de Rebentisch a este respecto, como las fuentes principales que nutren su propuesta en lo concerniente a una reinterpretación del fenómeno actual de la estetización de la política. Luego de este desarrollo, y tomando ahora un conjunto de elementos de la filosofía política de Miguel Abensour (2007; 1998), sugeriremos una interpretación alternativa de la democracia.
Eticidad y situacionalidad. Elementos para una crítica social
Authors: Yocca Francisco
Published: November 2024

En el presente artículo se propone, en un primer momento, llevar a cabo un recorrido reconstructivo de los sentidos y usos que elabora y aplica Hegel a su noción de ‘eticidad’ (Sittlichkeit), a través de su análisis en tres obras claves,  El sistema de la eticidad; en su Enciclopedia de las ciencia filosóficas, para finalmente abordar su tratamiento en las Líneas fundamentales de la filosofía del derecho. Esta noción clave mostrará su fertilidad en vistas al diagnóstico de época que lleva a cabo, en un intento de restituir el sentido y la integridad a la fragmentación de la sociedad de su tiempo.
Este primer paso permite, en un segundo momento, perseguir el hilo de actualización de esta idea hegeliana en la obra de Axel Honneth, en su vinculación con las ideas de la libertad y justicia. Siguiendo el modelo de una reconstrucción normativa que extrae de Hegel, se dará un paso más al proponer la formalización del concepto de eticidad para su productividad en el análisis social y debates teóricos contemporáneos.
Finalmente, el concepto formal de eticidad supone la tematización de aspectos que demandan un “enfoque situacional” como clave relevante de análisis que debe asumir una perspectiva crítica para una adecuada comprensión de los procesos sociales y políticos con determinaciones efectivas geo-histórico-políticas. La pretensión es poner en tensión el “concepto formal de eticidad” y los elementos de un “enfoque situacional” a los efectos de mostrar cómo la situación se constituye en horizonte de sentido para la asunción de un pensar crítico sobre la realidad.
Predictive Value of Thrombin Time in Early Preeclampsia
Authors: Li Yuting , Chen Yanli , Shu Hua , Zhang Xiaoyun , Li Peng , Wang Fengge , Man Dongmei
Published: November 2024

Background: Preeclampsia is a pregnancy-specific disease, which is easy to cause adverse outcomes in mother and child. Effective prediction of preeclampsia have important clinic al significance. This retrospective study aimed to investigate the utility of thrombin time during the first trimester as a predictive marker for preeclampsia. Methods: We meticulously examined the clinical characteristics of a cohort comprising 222 pregnant individuals with mild preeclampsia, 315 with severe preeclampsia, and 396 healthy pregnant women. Subsequently, we conducted both univariate and multiple regression analyses to discern variations in quantitative variables across these groups and to ascertain any discernible associations between thrombin time and the incidence of preeclampsia. Furthermore, we assessed the predictive performance of thrombin time by utilizing the receiver-operating characteristic (ROC) area under the curve (AUC). Results: Thrombin time exhibited a statistically significant prolongation in the preeclampsia cohort compared to the healthy pregnancy cohort (p < 0.05). This significance was maintained after adjusting for maternal age and gestation at testing in the logistic regression model. The AUC for thrombin time was found to be 0.953, with a commendable specificity of 97.28% and sensitivity of 92.48% in predicting preeclampsia. Conclusions: Our findings provide compelling evidence of a noteworthy association between prolonged thrombin time in the first trimester and an elevated risk of preeclampsia. The robust positive correlation underscores the potential of prolonged thrombin time as a predictive marker for the development of preeclampsia. Nevertheless, it is crucial to emphasize that further experimental studies are imperative to elucidate the underlying pathogenesis of thrombin time in the progression of preeclampsia.
Evaluation of Visceral Adipokines: Omentin, Vaspin, and Visfatin in Patients with Gestational Diabetes Mellitus
Authors: Yilmaz Mehmet , Aksin Serif , Bozbay Nizamettin , Balsak Deniz , Aboalhasan Yasmin , Kurnuç Fatma Zehra , Seyhan Leyla , Batmaz Ibrahim
Published: November 2024

Background: Gestational diabetes mellitus (GDM) is a common metabolic disorder characterized by glucose intolerance that develops during pregnancy. The underlying pathophysiological mechanisms of GDM involve complex interactions between genetic, environmental, and hormonal factors, including adipokines secreted by visceral adipose tissue. Omentin, vaspin, and visfatin are adipokines believed to influence insulin sensitivity and inflammation, though their precise relationship with GDM remains unclear. This study aimed to examine the association between these adipokines and GDM. Methods: This single-center, prospective controlled cohort study included 87 pregnant patients diagnosed with GDM via an oral glucose tolerance test (OGTT) between the 24th and 28th weeks of gestation, along with 87 control subjects without GDM. Serum levels of omentin, vaspin, and visfatin were measured using enzyme-linked immunosorbent assay (ELISA), and their association with GDM was analyzed. Results: Our results demonstrated that omentin levels were significantly higher in the GDM group compared to the control group (p = 0.012), while no significant differences were observed in vaspin and visfatin levels (p > 0.05). An omentin cut-off value of 29.0 ng/mL predicted GDM with 59.1% sensitivity and 59.1% specificity, suggesting its potential as a biomarker for GDM. Conclusions: This study underscores the unique role of omentin in GDM, in contrast to the non-significant changes observed in vaspin and visfatin levels. The elevated omentin levels in GDM patients suggest its potential as a biomarker for diagnosing and managing GDM. Further research is needed to elucidate the mechanisms through which omentin contributes to the pathophysiology of GDM. Clinical Trial Registration: NCT05463237, https://clinicaltrials.gov/study/NCT05463237.
The Role of Hyperemesis Gravidarum in the First-Trimester as a Predictor of Intrahepatic Cholestasis of Pregnancy
Authors: Küçükyurt Ayça Kubat , Kolcu Selma Atiye
Published: November 2024

Background: Intrahepatic cholestasis of pregnancy (ICP) and hyperemesis gravidarum (HEG) are pregnancy-specific liver diseases associated with significant fetal and maternal complications. Typically, HEG is diagnosed in the first trimester of pregnancy, and ICP in the third trimester of pregnancy. The aim of this study is to investigate whether primigravid women diagnosed with ICP between the 26th and 37th weeks of pregnancy were also diagnosed with HEG during the first trimester, and to evaluate whether the diagnosis of ICP can be predicted in pregnant women with a prior diagnosis of HEG. Methods: Our study is a retrospective analysis. A total of 4000 pregnant women, aged 18 to 45 years and between 26th and 37th weeks of gestation, who presented to the Gynecology and Obstetrics Clinic of the Health Sciences University, Istanbul Training and Research Hospital with complaints of pruritus between 01/07/2018 and 01/07/2023, were screened. 227 patients were diagnosed with ICP. Complete medical records and blood test results were available for 141 patients. 39 patients with a history of previous pregnancies and/or comorbidities, as well as 30 patients without available serum total bile acids (TBA) results, were excluded from the study. Of these, 72 pregnant women who met the inclusion criteria were enrolled in the study and grouped into primigravid women with and without a history of HEG in the first-trimester. Demographic characteristics, gestational age, detailed medical history, ultrasound findings, and biochemical parameters—including alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, bilirubin, and fasting bile acid (FBA) levels were statistically compared. Results: In our study, comparisons revealed no significant differences in AST, ALT, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and direct bilirubin levels (p > 0.05) between the groups with and without a history of HEG diagnosed with cholestasis. In pregnant women diagnosed with cholestasis, the total bilirubin and indirect bilirubin levels were significantly lower (p < 0.05) in the group with a history of HEG compared to the group without a history of HEG. In contrast, TBA levels were significantly higher (p < 0.05) in the group with a history of HEG compared to the group without a history of HEG. Conclusions: This study found that primigravid women with ICP and a history of HEG had elevated TBA levels, while total and indirect bilirubin levels were reduced. This suggests that patients with a history of HEG should be closely monitored in later stages of pregnancy for the development of ICP and potential liver damage. However, larger and more comprehensive studies are needed to confirm these findings.
Joint Analysis of CCAAT/Enhancer-Binding Protein Beta and Interleukin 1 Beta in the Treatment and Prognosis of Diffuse Large B-Cell Lymphoma
Authors: Wang Hongmin , Zhang Shuo , Wang Mengmeng , Wang Chaozhong , Xu Jihong , Jiang Ming , Han Xue , Yang Xiaotong , Zhang Liping , Chen Baotong , Liu Aichun
Published: November 2024

Objective: The purpose of this study is to investigate the correlation between elevated levels of CCAAT/enhancer-binding protein beta (CEBPB) gene expression and unfavorable outcomes in diffuse large B-cell lymphoma (DLBCL). The goal is to elucidate potential therapeutic targets associated with this relationship. Methods: Differential expression and survival analyses were conducted using data from the Gene Expression Omnibus (GEO) database. The functions of CEBPB in DLBCL cells were investigated through cell culture, RNA extraction, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. In addition, a weighted gene co-expression network analysis (WGCNA) was performed to pinpoint gene modules associated with CEBPB. Furthermore, experimental validation was carried out to explore the interaction between CEBPB and interleukin 1 beta (IL1B). Results: High levels of CEBPB expression are prominently observed in DLBCL, with its overabundance significantly linked to the diagnosis of DLBCL. Survival analysis reveals that patients exhibiting elevated CEBPB expression tend to experience a poorer prognosis. Further validation confirmed CEBPB's role in promoting DLBCL cell proliferation and cell cycle progression. WGCNA identified CEBPB-related gene modules, with IL1B identified as a potential regulatory gene of CEBPB. The presence of high levels of IL1B has been correlated with an unfavorable prognosis in individuals diagnosed with DLBCL. Experiments demonstrate that IL1B promotes DLBCL cell proliferation through CEBPB. Conclusions: This study reveals the significant roles of CEBPB and IL1B in DLBCL, providing new theoretical foundations and potential molecular targets for the treatment and prognosis of DLBCL.
Oncolytic Vesicular Stomatitis Virus: Optimisation Strategies for Anti-Cancer Therapies
Authors: Zinovieva Margarita , Ryapolova Anastasia , Karabelsky Alexander , Minskaia Ekaterina
Published: November 2024

Oncolytic viruses (OVs) represent a targeted anti-cancer therapy approach due to their ability not only to selectively infect and destroy malignant cells but also to induce an immune response. Vesicular stomatitis virus (VSV) offers a promising platform due to its low prevalence and pathogenicity in humans, lack of pre-existing immunity, easily manipulated genome, rapid growth to high titers in a broad range of cell lines, and inability to integrate into the host genome. However, despite its many advantages, many unresolved problems remain: problematic production based on the reverse genetics system, oncological selectivity, and the overall effectiveness of VSV monotherapy. This review will discuss various attempts at viral genome modifications aimed at improving the oncolytic properties of VSV. These strategies include inhibition of viral genes, modification of genes responsible for targeting cancer cells over healthy ones, insertion of foreign genes for boosting immune response, and changing the order of viral and inserted foreign genes. In addition, possible ways to improve VSV-based anti-tumor therapy and achieve higher efficiency will be considered by evaluating the effectiveness of various delivery methods as well as discussing treatment options by combining VSV with other groups of anticancer drugs.
Circulating Extracellular Vesicles: An Effective Biomarker for Cancer Progression
Authors: Chatterjee Madhura , Gupta Saurabh , Nag Sayoni , Rehman Ishita , Parashar Deepak , Maitra Arindam , Das Kaushik
Published: November 2024

Extracellular vesicles (EVs), the ubiquitous part of human biology, represent a small heterogenous, membrane-enclosed body that contains a diverse payload including genetic materials in the form of DNA, RNAs, small non-coding RNAs, etc. mostly mirroring their source of origin. Since, a vast majority of research has been conducted on how nucleic acids, proteins, lipids, and metabolites, associated with EVs can be effectively utilized to identify disease progression and therapeutic responses in cancer patients, EVs are increasingly being touted as valuable and reliable identifiers of cancer biomarkers in liquid biopsies. However, the lack of comprehensive clinical validation and effective standardization protocols severely limits its applications beyond the laboratories. The present review focuses on understanding the role of circulating EVs in different cancers and how they could potentially be treated as cancer biomarkers, typically due to the presence of bioactive molecules such as small non-coding RNAs, RNAs, DNA, proteins, etc., and their utilization for fine-tuning therapies. Here, we provide a brief general biology of EVs including their classification and subsequently discuss the source of circulatory EVs, the role of their associated payload as biomarkers, and how different cancers affect the level of circulatory EVs population.
LncRNA-TUG1: Implications in the Myocardial and Endothelial Cell Oxidative Stress Injury Caused by Hemorrhagic Shock and Fluid Resuscitation
Authors: Li Wei , Chen Huaiyu , Zhu Xueli , Lin Mingrui
Published: November 2024

Background: LncRNA taurine-upregulated gene 1 (TUG1) can regulate vascular endothelial cell injury, a critical mechanism in treating hemorrhagic shock and fluid resuscitation (HS/R). Therefore, this study explored the influence of TUG1 in HS/R. Methods: An in vivo rat model of ischemia-reperfusion (I/R) injury post-HS/R and an in vitro model of oxidative stress injury in rat cardiomyocyte cell line (H9C2) were constructed. In vivo, we silenced TUG1 and quantified its expression along with inflammatory factors through quantitative reverse transcription polymerase chain reaction (qRT-PCR), mean arterial pressure (MAP) detection and blood gas analysis. Myocardial functional impairment was assessed via Triphenyl-2H-Tetrazolium Chloride (TTC), Hematoxylin and eosin, and Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) stainings. Oxidative stress level in rat serum was measured. In vitro, we examined the changes of cell viability, apoptosis, oxidative stress levels, inflammatory factor secretion and nuclear factor-κB (NF-κB)/p65 expression by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, Enzyme-linked immunosorbent assay (ELISA) and Western blot. Results: TUG1 level was elevated in rats of I/R model caused by HS/R. TUG1 silencing ameliorated the decline in MAP, acid-base imbalance and myocardial tissue damage, and suppressed oxidative stress and inflammatory factor levels in model rat. TUG1 silencing enhanced viability, impeded apoptosis, and reduced oxidative stress, inflammatory factor contents and NF-κB/p65 expression in H2O2 treated H9C2 cells. Conclusion: TUG1 participates in regulating oxidative stress damage and inflammation induced by HS/R.
Formation of the Native Topology of a Protein is due to the “Conserved but Non-Functional” Residues: A Case of Apomyoglobin Folding
Authors: Bychkova Valentina E. , Dolgikh Dmitry A. , Balobanov Vitalii A. , Finkelstein Alexei V.
Published: November 2024

This paper is dedicated to the memory of Oleg B. Ptitsyn (1929-1999) and presents an answer to his question: “What is the role of conserved non-functional residues in protein folding?”. This answer follows from the experimental works of three labs. The role of non-functional but conserved residues of apomyoglobin (apoMb) in the formation of the native protein fold in the molten globule state has been experimentally revealed. This research proves that the non-functional but conserved residues of apoMb are necessary for the formation and maintenance of the correct topological arrangement of the main elements in the apoMb secondary structure already in the early folding intermediate.
The Effects of Dexamethasone on Human Lens Epithelial Cells and the Analysis of Related Pathways with Transcriptome Sequencing
Authors: Shu Xinjie , Gao Jiamin , Xu Han , Li Qiyou , Gong Yu , Li Jiawen
Published: November 2024

Background: The goal of this study was to investigate the effects of dexamethasone on human lens epithelial cells (HLECs) and the potential mechanisms. Methods: HLECs (HLE-B3) were cultured in vitro to assess the effects of dexamethasone on cell size at different concentrations. Immunofluorescence staining was used to detect specific protein expression in HLE-B3 cells. The cell size was observed using phase-contrast microscopy, and the length and area were quantitatively measured with ImageJ software for statistical analysis. Flow cytometry was used to verify these outcomes. The means of three groups were statistically analyzed using one-way analysis of variance, whereas the means of two groups were statistically analyzed with the parametric Student’s t-test. Additionally, high-throughput transcriptome sequencing was performed to compare messenger RNA (mRNA) expression levels between different concentrations of dexamethasone treatment groups and the control group, to identify potential signaling pathways. Subsequently, we performed quantitative Polymerase Chain Reaction (qPCR), immunofluorescence staining, and molecular docking experiments on the key differentially expressed genes. Results: Dexamethasone affected the size of HLE-B3 cells. Both 0.25 and 0.5 μmol/L dexamethasone increased cell length and area, exhibiting no significant difference between the two treatment groups. Flow cytometry showed that dexamethasone increased cell size and granularity, with 0.25 μmol/L dexamethasone leading to larger cell areas and higher intracellular granularity. High-throughput transcriptome sequencing revealed significant upregulation of lysophosphatidic acid receptor 1 (LPAR1) and the pathways related to the glucocorticoid (GC) receptor. Conclusions: Certain concentrations of dexamethasone impact the morphology and biological functions of HLECs. As a subtype of G protein-coupled receptors, LPAR1 on the cell membrane may interact with dexamethasone, affecting cell size and inhibiting autophagy via the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. These discoveries offer crucial biological insights into how dexamethasone influences the morphology and function of HLECs and the pathogenesis of GC-induced cataracts, offering potential molecular targets for future therapeutic strategies.
Signal Transduction Mechanisms of Focal Adhesions: Src and FAK-Mediated Cell Response
Authors: Katoh Kazuo
Published: November 2024

Cell-to-substrate adhesion sites, also known as focal adhesion sites (FAs), are complexes of different proteins on the cell surface. FAs play important roles in communication between cells and the extracellular matrix (ECM), leading to signal transduction involving different proteins that ultimately produce the cell response. This cell response involves cell adhesion, migration, motility, cell survival, and cell proliferation. The most important component of FAs are integrins. Integrins are transmembrane proteins that receive signals from the ECM and communicate them to the cytoplasm, thus activating several downstream proteins in a signaling cascade. Cellular Proto-oncogene tyrosine-protein kinase Src (c-Src) and focal adhesion kinase (FAK) are non-receptor tyrosine kinases that functionally interact to promote crucial roles in FAs. c-Src is a tyrosine kinase, activated by autophosphorylation and, in turn, activates another important protein, FAK. Activated FAK directly interacts with the cytoplasmic domain of integrin and activates other FA proteins by attaching to them. These proteins activated by FAK then activate other downstream pathways such as mitogen-activated protein kinase (MAPK) and Akt pathways involved in cell proliferation, migration, and cell survival. Src can induce detachment of FAK from the integrin to increase the focal adhesion turnover. As a result, the Src-FAK complex in FAs is critical for cell adhesion and survival mechanisms. Overexpression of FA proteins has been linked to a variety of pathological disorders, including cancers, growth retardation, and bone deformities. FAK and Src are overexpressed in various cancers. This review, which focuses on the roles of two important signaling proteins, c-Src and FAK, attempts to provide a thorough and up-to-date examination of the signal transduction mechanisms mediated by focal adhesions. The author also described that FAK and Src may serve as potential targets for future therapies against diseases associated with their overexpression, such as certain types of cancer.
Molecular Insights into Tau Pathology and its Therapeutic Strategies in Alzheimer's Disease
Authors: Zhou Futao , Zhao Yushi , Sun Yangyan , Chen Wanjiao
Published: November 2024

Alzheimer’s disease (AD) is the most common cause of dementia. The two major hallmarks of this disease are extracellular amyloid plaques and intracellular neurofibrillary tangles in the brain, accompanied by loss of neurons and synapses. The plaques and tangles mainly consist of amyloid-β (Aβ) and tau protein, respectively. Most of the therapeutic strategies for AD to date have focused on Aβ. However, there is still no effective therapy available. In recent years, the clinical therapeutic failure of targeting Aβ pathology has resulted in increased interest towards tau-based therapeutics. In the current review, we focus on the research progress regarding the pathological mechanisms of tau protein in this disease and discuss tau-targeting therapeutic strategies.
A Mendelian Randomization Study about Causal Associations between Tofu Consumption and Stroke as well as Related Subtypes
Authors: Wang Yan , Liu Yunlong , Xia Mingwu , Cao Shugang
Published: November 2024

Objective: Consuming soy in the diet is beneficial for health, and tofu possess the richest source of dietary soy. However, the specific association with stroke and related subtypes remains controversial. In this study, the genetic causal relationship among tofu and stroke as well as the subtypes was investigated by utilizing the data in a number of genome-wide association study (GWAS) based on population. Methods: The tofu intake GWAS analysis is derived from the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol (MRC-IEU) Consortium. The two-sample Mendelian randomization (MR) study was carried out, utilizing multiple analysis methods to analyze the associations with stroke and related subtypes. The sensitivity, heterogeneity, and potential pleiotropy could be investigated by multiple analysis method. Results: We found that tofu intake had no causal relationship with stroke. However, in stroke subtype, there is a causal relationship among tofu intake with the risk of intracerebral hemorrhage (ICH) (odds ratio, OR = 1.24 × 10-5, 95% CI: 1.54 × 10-8–9.95 × 10-3, p = 9.300 × 10-4), while tofu intake does not affect the risk of ischemic stroke (OR = 1.07 × 10-1, 95% CI: 3.84 × 10-4–2.97 × 101, p = 4.362 × 10-1) and subarachnoid hemorrhage (SAH) (OR = 3.33 × 10-3, 95% CI: 1.79 × 10-6–6.18, p = 1.373 × 10-1). Both the Mendelian randomization PRESSO (MR-PRESSO) global test and Cochran's Q test did not detect any sensitivity and heterogeneity. Conclusions: While tofu consumption is associated with a higher risk of ICH, it does not show a significant relationship with ischemic stroke or SAH. The varying effects of tofu on different stroke subtypes underscore the need for considering potential confounding dietary and lifestyle factors in future studies.
The Role of Microglia and Astrocytes in the Pathomechanism of Neuroinflammation in Parkinson’s Disease—Focus on Alpha-Synuclein
Authors: Harackiewicz Oliwia , Grembecka Beata
Published: November 2024

Glial cells, including astrocytes and microglia, are pivotal in maintaining central nervous system (CNS) homeostasis and responding to pathological insults. This review elucidates the complex immunomodulatory functions of glial cells, with a particular focus on their involvement in inflammation cascades initiated by the accumulation of alpha-synuclein (α-syn), a hallmark of Parkinson’s disease (PD). Deriving insights from studies on both sporadic and familial forms of PD, as well as animal models of PD, we explore how glial cells contribute to the progression of inflammation triggered by α-syn aggregation. Additionally, we analyze the interplay between glial cells and the blood-brain barrier (BBB), highlighting the role of these cells in maintaining BBB integrity and permeability in the context of PD pathology. Furthermore, we delve into the potential activation of repair and neuroprotective mechanisms mediated by glial cells amidst α-syn-induced neuroinflammation. By integrating information on sporadic and familial PD, as well as BBB dynamics, this review aims to deepen our understanding of the multifaceted interactions between glial cells, α-syn pathology, and CNS inflammation, thereby offering valuable insights into therapeutic strategies for PD and related neurodegenerative disorders.
Precise 3D Localization of Intracerebral Implants Using a Simple Brain Clearing Method
Authors: Catanese Julien , Murakami Tatsuya C. , Catto Adam , Kenny Paul J. , Ibañez-Tallon Ines
Published: November 2024

Background: Precise localization of intracerebral implants in rodent brains is required for physiological and behavioral studies, particularly if targeting deep brain nuclei. Traditional histological methods, based on manual estimation through sectioning can introduce errors and complicate data interpretation. Methods: Here, we introduce an alternative method based on recent advances in tissue-clearing techniques and light-sheet fluorescence microscopy. This method uses a simplified recipe of the Clear, Unobstructed Brain/Body Imaging Cocktails and Computational Analysis (CUBIC) method, which is a rapid clearing procedure using an aqueous-based solution compatible with fluorescence and fluorescence markers. We demonstrate the utility of this approach in anesthetized transgenic mice expressing channelrhodopsin-2 (ChR2) and enhanced yellow fluorescent fusion (EYFP) protein under the choline acetyltransferase (ChAT) promoter/enhancer regions (ChAT-ChR2-EYFP mice) with implanted linear silicon optrode probes into the midbrain interpeduncular nucleus (IPN). Results: By applying the red fluorescent DiD' dye (DiIC18(5) solid (1,1′-Dioctadecyl-3,3,3′,3′-Tetramethylindodicarbocyanine, 4-Chlorobenzenesulfonate Salt) to the electrode surface, we precisely visualize the electrode localization in the IPN of ChAT-ChR2-EYFP mice. Three-dimensional brain videos from different orientations highlight the potential of this method. Optogenetic responses recorded from electrodes placed in the IPN validate these findings. Conclusions: This method allows for precise localization of brain implantation sites in transgenic mice expressing cell-specific fluorescence markers. It enables virtual brain slicing in any orientation, making it a useful tool for functional studies in mice.
Comparison of Sutureless Aortic Valve Replacement and Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-Analysis of Propensity Score Matching
Authors: Liu Shidong , Chen Hao , Zhou Wenjun , Zhao Pengying , Qi Liang , Zhang Yalan , Song Bing , Yu Cuntao
Published: November 2024

Background: To evaluate the clinical outcomes of sutureless aortic valve replacement (SUAVR) and transcatheter aortic valve implantation (TAVI). Methods: We systematically searched the electronic database and the Clinical Trials Registry up to 31 February 2023. Random effects model risk ratio (RR) and mean differences (MD) with corresponding 95% confidence intervals (CIs) were pooled for the clinical outcomes. Results: The included 16 studies using propensity-matched analysis consisted of 6516 patients, including 3258 patients in the SUAVR group and 3258 patients in the TAVI group. The SUAVR group had lower mortality than the TAVI group at 1-year [RR = 0.53, 95% CI (0.32, 0.87), I2 = 49%, p = 0.01], 2-year [RR = 0.56, 95% CI (0.37, 0.82), I2 = 51%, p = 0.03] and 5-year [RR = 0.56, 95% CI (0.46, 0.70), I2 = 0%, p < 0.01]. The SUAVR group had a significantly lower rate of new permanent pacemaker implantation (PPI) [RR = 0.74, 95% CI (0.55, 0.99), I2 = 48%, p = 0.04], moderate-to-severe paravalvular leak (PVL) [RR = 0.18, 95% CI (0.11, 0.30), I2 = 0%, p < 0.01], more-than-mild residual aortic regurgitation (AR) [RR = 0.27, 95% CI (0.14, 0.54), I2 = 0%, p < 0.01]. In addition, the SUAVR group had a higher rate of new-onset atrial fibrillation (AF) [RR = 3.66, 95% CI (1.95, 6.89), I2 = 84%, p < 0.01], major or life-threatening bleeding event [RR = 3.63, 95% CI (1.81, 7.28), I2 = 83%, p < 0.01], and higher postoperative mean aortic gradient [MD = 1.91, 95% CI (0.73, 3.10), I2 = 91%, p < 0.01] than the TAVI group. Conclusions: The early and mid-term clinical outcomes of SUAVR were superior compared to TAVI. Further studies should be conducted to highlight the specific subgroups of patients. that will benefit from each technique. INPLASY Registration Number: INPLASY 2022110058 (https://inplasy.com/inplasy-2022-11-0058/).
The Role of Exercise in Regulating the Generation of Extracellular Vesicles in Cardiovascular Diseases
Authors: Shen Peng , Qiu Yue , Sun Yan-Yan , Jiang Yue-Ying , Guan Xiu-Mei , Cheng Min , Wang Yan-Xia
Published: November 2024

Extracellular vesicles (EVs) are nanoscale vesicles released by cells, which play an important role in intercellular communication by transporting proteins, lipids, nucleic acids, and other molecules. Different intensities of exercise can induce the release of EVs from cells and tissues, such as endothelial cells, skeletal muscle and adipose tissue, hepatocytes, immune cells, and neuronal cells. Exercise-induced EVs exert cardiovascular protective effects such as anti-inflammatory and anti-oxidative by altering their contents. This paper reviews the cell and tissue sources of EVs induced by exercise of different intensities, the regulatory effects of different exercise intensities on EVs, and their mechanisms of action in cardiovascular diseases. The aim is to provide new insights for the treatment of cardiovascular diseases and offer scientific evidence for the construction of engineered EVs mimicking the effects of exercise.
Gut Commensal Bacteroides thetaiotaomicron Promote Atherothrombosis via Regulating L-Tryptophan Metabolism
Authors: Liu Honghong , Feng Siqin , Tang Muyun , Tian Ran , Zhang Shuyang
Published: November 2024

Background: Coronary thrombosis events continue to be the leading cause of morbidity and mortality worldwide. Recently, emerging evidence has highlighted the role of gut microbiota in cardiovascular disease, but few studies have systematically investigated the gut microbiota variation associated with atherothrombosis. Methods: We conducted multi-omics analysis (metagenomics sequencing and serum metabolomics) on 146 subjects from Peking Union Medical College Hospital-Coronary Artery Disease (PUMCH-CAD) cohort. We analyzed the key strains and metabolic pathways related to coronary artery disease (CAD) development, explored the bacterial functional pathway which contributes to atherothrombosis at strain level in depth. Single strain colonization procedures on germ free mice demonstrated the promotion of platelet activation and thrombotic phenotypes of the disordered gut microbiota. Results: Gut microbiome and serum metabolome shifts were apparent in cases of CAD progression, Bacteroides spp. disturbed the development of CAD by participating in lipopolysaccharide (LPS), menaquinone and methanogenesis pathways. Particularly, coronary thrombosis is characterized by increased circulatory levels of L-tryptophan, which correlate with Bacteroides thetaiotaomicron that has enriched biosynthetic potential. In germ free mice we demonstrate that Bacteroides thetaiotaomicron colonization could induce thrombosis, aggravate platelet hyperreactivity and augment fecal levels of L-tryptophan. Conclusions: The disordered gut microbiota of CAD contributed to the occurrence and development of atherothrombosis. The key members of the bacterial and metabolic features may become biomarkers for predicting the cardiovascular thrombosis event. Targeting the microbial pathway may have the potential to reduce the incidence of cardiovascular disorders. Clinical Trial Registration: ChiCTR2000033897, https://www.chictr.org.cn/showproj.html?proj=55023.
Prognostic Value of Left Ventricular Myocardial Strain Parameters Derived from Cardiac Magnetic Resonance Feature Tracking Technique in Light-Chain Cardiac Amyloidosis Patients: A Pilot Study
Authors: Nai Rile , Liu Jia , Zhao Kai , Ma Shuai , Ma Wei , He Jiangkai , Xu Shasha , Lian Jianxiu , Li Wei , Qiu Jianxing
Published: November 2024

Background: Previous research on the prognostic implications of left ventricular myocardial strain using cardiac magnetic resonance feature tracking (CMR-FT) in light-chain cardiac amyloidosis (AL-CA) has shown promising potential. This study aimed to evaluate the prognostic significance of global and segmental left ventricular myocardial strain in AL-CA patients, specifically analyzing the American Heart Association's 16 segments. Methods: A total of 75 consecutive patients (50 men, mean age: 55.6 ± 10.0 years) who underwent CMR examination with histologically confirmed systemic AL-CA were retrospectively enrolled between January 2014 and November 2022. Both global and segmental myocardial strain and the American Heart Association’s 16 segments were quantified using CMR-FT on the steady-state free precession (SSFP) cine sequence. A comparative analysis was conducted between survivors and non-survivors based on the defined endpoint. Student t-test or Mann–Whitney U, receiver operating characteristic curve, Kaplan–Meier event-free survival curve, and Cox proportional hazards regression were used. Significance was set at p < 0.05. Results: Following a median follow-up of 34 months, 16 out of 75 patients experienced mortality events. B-type natriuretic peptides (BNP) (p < 0.001), global radial strain (RSglobal) (p = 0.033), and RS in the basal inferior segment (RSbas-inferior) (p = 0.025) remained significant as independent predictors of all-cause mortality. The cut-off values were identified as 24.97% for RSglobal, and 20.97% for RSbas-inferior. Kaplan–Meier survival curves revealed significantly reduced event-free survival for individuals in the lower cut-off groups for RSglobal and RSbas-inferior (p = 0.013, p < 0.001, respectively). Conclusions: Radial strain for the global and the basal inferior segment may prove valuable for risk stratification in patients with AL-CA.
Clinical Decision Making and Technical Approaches in Implantable Cardioverter-Defibrillator Procedures: A Step by Step Critical Appraisal of Literature
Authors: Roseboom Eva , Smit Marcelle D. , Groenveld Hessel F. , Rienstra Michiel , Maass Alexander H.
Published: November 2024

The selection of an appropriate implantable cardioverter-defibrillator (ICD) type and implantation strategy involves a myriad of considerations. While transvenous ICDs are standard, the rise of non-transvenous options like subcutaneous ICDs and extravascular ICDs is notable for their lower complication rates. Historical preferences for dual chamber ICDs have shifted to single-chamber ICDs. Single-coil ICDs are preferred for easier extraction, and the use of the DF-4 connector is generally recommended. Cephalic cutdown is the preferred venous access technique, while axillary vein puncture is a viable alternative. The right ventricular apex remains the preferred lead position until further evidence on conduction system pacing emerges. Left-sided, subcutaneous ICD implantation is considered reliable, contingent on specific cases. A meticulous perioperative plan, including antibiotic prophylaxis and an antithrombotic regimen, is crucial for successful implantation.