bluuebunny/crossref_metadata_2025 huggingface dataset:
"TÃO NEGRO QUE É AZUL": ANÁLISE SEMIÓTICA DE POOR MISS FINCH (1872), DE WILKIE COLLINS
Authors: Louro da Silva Yasmine Sthéfane , Barreto Costa Diana
Published: February 2025

A presente pesquisa tem como objetivo analisar a obra Poor Miss Finch (1872), de Wilkie Collins, a fim de identificar as relações étnico-raciais entre os personagens da obra, em especial da protagonista, Lucilla Finch, sendo estas positivas ou negativas, por meio do Percurso Gerativo de Sentido Semiótico de Greimas, em conformidade com Barros (2005). Na fundamentação teórica, para a contextualização do período histórico-social retratado por Collins (1872) na sua obra, nortear-se-á a pesquisa pelos estudos de Brophy (2019), Durgan (2015), Gladden (2005), Kling (1966) e Nayder (2003), para evidenciar as relações imperialistas entre Índia e Inglaterra e denunciar as práticas racistas e de intolerância religiosa, realizadas no período denominado Revolta do Índigo (1859-1862), em que soldados indianos, os chamados cipaios, eram continuamente desrespeitados e perseguidos, influenciando no inconsciente coletivo dos ingleses, que passaram a considera-los uma raça inferior. Como resultado, obteve-se que Miss Finch, mesmo cega, mantém crenças racistas sobre as chamadas pessoas escuras. Ironicamente, Lucilla se apaixona por Oscar, um pintor que se mudou para a casa ao lado a dela, que, após um assalto, desenvolve convulsões graças a um traumatismo craniano, impedindo-o de casar-se com ela. Como considerações finais, compreende-se que o fato de terminar com Oscar, o irmão gêmeo que é literalmente azul, mostra que ela superou o seu preconceito, assim como os ingleses poderiam superar as suas crenças problemáticas e racistas sobre os indianos.
A taxatividade das hipóteses legais do Agravo de Instrumento no Novo Código de Processo Civil: Uma análise das consequências de sua implementação tendo em vista os princípios do contraditório e da ampla defesa
Authors: Santos Liliane Araújo Marques dos , Nascimento Júnior Hermengardo
Published: February 2025

Discute a aplicabilidade do agravo de instrumento em consonância com o devido processo legal, levando em conta a inovadora sistemática das hipóteses taxativas elencadas no Novo Código de Processo Civil, que busca efetivar o princípio da celeridade processual. Analisa a aplicabilidade do novo diploma legal e as consequências sobre os princípios constitucionais do contraditório e ampla defesa, que viabilizam a concretização do devido processo legal. Discute sobre a taxatividade do novo agravo de instrumento e a possível chance de fragilizar a segurança jurídica. Por fim aborda o juízo de proporcionalidade entre vantagens e desvantagens da adoção de um instrumento jurídico cujas hipóteses vêm estritamente delimitadas em texto legal cabível contra decisão interlocutória
Pensão de Equidade e Pensão Reparatória: outro olhar para os denominados alimentos compensatórios e uma análise comparativa entre o Brasil e alguns sistemas jurídicos
Authors: Lira Wlademir Paes de
Published: February 2025

Analisa o conceito e a natureza jurídica do instituto denominado alimentos compensatórios, no Brasil e em outros sistemas jurídicos. Discorre sobre os conceitos, espécies e natureza de alimentos e alimentos compensatórios. Conclui que os alimentos compensatórios surgem, ora como forma de evitar significativo desequilíbrio econômico e financeiro entre as partes, após o fim da relação familiar, ora como forma de minimizar os prejuízos que um dos cônjuges sofre, enquanto o outro administra sozinho o patrimônio comum, até a efetivação da partilha.
A MONITORAÇÃO ELETRÔNICA DE PRESOS NA PROGRESSÃO PARA O REGIME SEMIABERTO NO ESTADO DE ALAGOAS
Authors: Costa Elaine Cristina Pimentel , Sampaio João Marcos Francisco
Published: February 2025

O presente trabalho buscou compreender a eficácia social do monitoramento eletrônico de apenados que cumprem pena em regime semiaberto em Alagoas. Para tanto, realizou-se estudo teórico sobre a monitoração eletrônica no País, bem como a legislação e jurisprudência pertinentes, sobretudo o RE 641.320 RS. Além disso, foram realizadas entrevistas semiestruturadas com o Juiz de Execução Penal e com apenados que aguardavam a colocação da tornozeleira e foram observadas audiências admonitórias.A pesquisa demonstrou que a vigilância eletrônica não produz os efeitos sociais oficialmente alegados, não se justificando, então, o investimento público realizadocomo substitutivo do cumprimento da pena em estabelecimento adequado ao regime semiaberto.
DROGAS E SUA REPERCUSSÃO NO MUNDO ECONÔMICO E POLÍTICO: COMO O PROBLEMA PRECISA SER PENSADO
Authors: Marques Karla Padilha Rebelo
Published: February 2025

São analisados os aspectos econômico, político e social da droga, com foco na realidade brasileira e em suas peculiaridades geográficas e institucionais. Buscam-se identificar as relações existentes entre a droga, a corrupção e a violência, muito mais robustas em países com baixos índices de desenvolvimento e com precário atendimento às necessidades básicas da população. Este estudo, através de revisão bibliográfica especializada, conclui pela necessidade de reengenharia da política anti-drogas, buscando-se fugir de uma abordagem eminentemente repressiva e punitivista em direção a intervenções que apontem para alternativas mais racionalmente eficazes no enfrentamento da nefasta influência exercida pelo mundo das drogas, em todas as esferas de poder.
A TEORIA DO FATO JURÍDICO, O NEGÓCIO JURÍDICO PROCESSUAL E O PROCESSO DO TRABALHO
Authors: Aguiar Nathália de Araújo Oliveira de Oliveira , Souza Cecília Monte Xavier de
Published: February 2025

As normas jurídicas trazem em seu conteúdo a descrição de suportes fácticos que, ao ocorrem no mundo dos fatos, sofrem a incidência das normas, tornando-se fatos jurídicos. Temos que os fatos jurídicos lato sensu lícitos se dividem em fato jurídico em sentido estrito, ato-fato jurídico e ato jurídico, subdividindo-se este último ainda em ato jurídico em sentido estrito e negócio jurídico. Provocado pela inovação trazida no art. 190 do CPC/2015, este estudo busca analisar o negócio jurídico processual à luz da Teoria do Fato Jurídico, verificando a possibilidade ou não de sua aplicação ao processo do trabalho.
Critical evaluation of quality by design software
Authors: Daram Sushma Reddy  , Vadla Pranay Kumar  , Thalaari Shyam  , Vadagam Chandana  , Trunugu Sai Priya  , Vankunavath Sandeep
Published: February 2025

Quality by design (QbD) represents the modern approach to ensuring pharmaceutical quality. This concept has significantly influenced the progress of pharmaceutical sciences, having been established and applied globally in accordance with the International Conference on Harmonization (ICH) Guidelines. The proposed ICH guidelines—Q8 for pharmaceutical development, Q9 for quality risk management, and Q10 for pharmaceutical quality systems—provide a foundation for integrating quality into products.

In the QbD framework, it is crucial to define the desired product performance profile, known as the Target Product Profile (TPP), and the Target Product Quality Profile (TPQP), as well as to identify Critical Quality Attributes (CQA). Based on this, we can design both the product formulation and the process to meet these attributes. This leads to recognizing the impact of raw material Critical Material Attributes (CMA) and Critical Process Parameters (CPP) on the CQAs, and identifying sources of variability
Determining the role of Gynaecologists in peri-operative oral functional management (POFM) of Pre-eclampsia: A cross-sectional survey
Authors: Bindu S Patil  , Vaishnavi Chincholi  , Laxmi Machetty  , Girija R Giri  , Jyothilaxmi Patil
Published: February 2025

Background and objectives: Pre-eclampsia affects 5–15% of pregnancies in India, significantly contributing to maternal morbidity and mortality. Research by Swetha Tanneeru et al. identified periodontal microbial components in subgingival plaque and placental tissue, linking periodontitis as a key risk factor for pre-eclampsia. Managing patients with Peri-operative Oral Functional Management (POFM) reduces microbial loads, emphasizing oral health's role in mitigating pre-eclampsia risks. Identifying periodontal disease and considering POFM reduces microbial load. With this hypothesis we aimed to assess knowledge of periodontal disease as a risk factor among gynaecologists in pre-eclampsia.

Methods: A Google-based questionnaire survey was distributed to gynaecologists in Kalaburagi, targeting professionals irrespective of experience or institution type. The 17-question survey assessed knowledge of periodontal disease's role in pre-eclampsia, attitudes toward periodontal care and willingness to collaborate with dental specialists.

Results: SPSS analysis revealed 45% of gynaecologists were aware of pre-eclampsia prevalence, with 52.1% recognizing its association with periodontal infections. However, only 35.6% were informed about POFM's role. Encouragingly, 98.6% supported interdisciplinary collaboration with periodontists.

Conclusion: The study highlights gaps in knowledge and practices regarding periodontal care in pre-eclampsia management. Periodontal health is vital in preventing complications like preterm low birth weight and developmental deformities. Gynaecologists acknowledged the importance of integrating periodontal care and supported its prioritization through referrals to periodontists. The findings underscore the need for multicentric studies and educational initiatives to promote POFM and interdisciplinary approaches, potentially reducing maternal morbidity and mortality associated with pre-eclampsia.
Phytochemical and anti-bacterial screening of two traditional rice varieties, Chitti Muthyalu and Khetri Maharaj
Authors: Madhavi Latha Maragani  , Narendra Kelam  , Zeenath Khan  , Sneha Latha Gujjarlapudi  , Mallikarjuna Kokkanti
Published: February 2025

Rice is a staple crop for most of the world's population, with a rich history dating back to ancient times. In India, traditional rice varieties like Chitti Muthyalu and Khetri Maharaj are renowned for their distinct aroma and medicinal properties. However, their detailed potential for phytochemical and antimicrobial activities remains largely unexplored. This study investigated the methanolic seed extracts from two rice varieties for qualitative phytochemical composition and antibacterial properties. The preliminary phytochemical assessment revealed the presence of various bioactive compounds, including amino acids, alkaloids, proteins, carbohydrates, flavonoids, cardiac glycosides, saponins, tannins, and terpenoids. Antibacterial screening showed that both rice varieties exhibited significant activity against Bacillus subtilis, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa. These findings suggest that both rice varieties are rich in phytochemicals with potential antibacterial properties.
Estimation of effective thermal conductivity for porous material
Authors: Rajlaxmi Chaudhary’s  , SD. Patle
Published: February 2025

In this study, an algebraic expression for the effective thermal conductivity (ETC) of two-phase porous materials is derived using a two-layer model, which is analogous to the electrical resistance in an electrical circuit. This analytical approach enables the evaluation of the ETC through the proposed algebraic expression for two-dimensional porous media. The geometries under consideration include arrays of non-touching in-line and staggered square and circular cylinders, as well as touching hexagonal arrangements, rectangular grilles, criss-cross grilles, hexagons, and touching square cylinders. Comparison of the results obtained from the proposed algebraic expression with existing numerical solutions demonstrates excellent agreement.
Comparative study of dynamic behaviour of PMSM drive using linear quadratic regulator (LQR) based state feedback control (SFC) with different integral control actions
Authors: Das Pranjal , Hazra Soujanya , Thapa Akshat , Sadhukhan Archak , Sarkar Prem Kumar , Gayen Pritam Kumar
Published: February 2025

The goal of this work is to compare the dynamic performances of a permanent magnet synchronous motor (PMSM) drive under various operating conditions by using different integral control actions with linear quadratic regulator (LQR) based state feedback control (SFC) technique. At first, the LQR-based conventional SFC method is used for the optimal speed control of the electric drive. Here, the transient performance of speed variations is satisfactory, but the steady state error is noticed. Therefore, a proportional-integral (PI) controller is used along with the LQR-SFC process for controlling the q-axis current of the motor. This reduces the steady state error at the expense of increased speed overshoot and settling time. Then, the LQR-SFC technique with integration of speed error (ISE)is used for controlling the speed of the motor. Here, superior transient as well as steady speed response is achieved. Next, the dynamic performances of PMSM are tested and compared between the two integral actions based LQR-SFC controllers (LQR-SFC-PI and LQR-SFC-ISE) under low- and high-speed references in MATLAB-SIMULINK software platform. The various results indicate their relative dynamic performances under the test conditions.
Pharmacokinetics of Oral and Subcutaneous Carprofen in Common Marmosets (Callithrix jacchus)
Authors: Perminov Ekaterina , Adamson Trinka W , Lee Kuo Fen
Published: February 2025

The common marmoset (Callithrix jacchus) is an increasingly popular animal model, and while carprofen is a frequently used NSAID in this species, there are no published studies evaluating dosage needs to achieve appropriate analgesia. The aim of this study was to determine the pharmacokinetics of low-dose (2 mg/kg) and high-dose (4 mg/kg) carprofen following oral and subcutaneous routes of administration in marmosets. Three (2 females, 1 male) adult (3.1 ± 1.6 y old [mean ± SD]) common marmosets were used for this study. Blood was collected at 0, 1, 2, 4, 6, 12, and 24 h after administration. The plasma concentrations of carprofen were determined using HPLC and pharmacokinetic parameters. The 4 mg/kg carprofen yielded a significantly higher plasma concentration than did 2 mg/kg carprofen. However, our data show that neither administration route, nor dose, result in plasma concentrations at or above the desired therapeutic threshold. The poor pharmacokinetic properties suggest that these doses of carprofen are not adequate and that either higher doses should be considered or carprofen should not be used as the NSAID of choice in the common marmoset.
The use of microstrip and fractal antennas based on metamaterials in digital communication systems to increase their energy efficiency
Authors:   Far Eastern Federal University, 690922, Primorsky Krai, Vladivostok, Russkiy Island, Ayaks settlement, 10, Sever D.S. , Dronin Ya.S. ,   Far Eastern Federal University, 690922, Primorsky Krai, Vladivostok, Russkiy Island, Ayaks settlement, 10, Statsenko L.G. ,   Far Eastern Federal University, 690922, Primorsky Krai, Vladivostok, Russkiy Island, Ayaks settlement, 10, Rodionov A.Yu. ,   Far Eastern Federal University, 690922, Primorsky Krai, Vladivostok, Russkiy Island, Ayaks settlement, 10
Published: February 2025

The possibility of using metamaterials in the construction of microstrip and fractal antennas is investigated. The variations of the introduction of metamaterials considered in the work make it possible to achieve increased energy efficiency of digital communication systems, which makes it possible to create devices with improved characteristics and expanded functionality. Various variants of microstrip and fractal antenna devices were modeled using CST Studio software, which meet modern requirements for optimizing the size and improving radiation parameters. The paper considers two structures: a torn ring resonator (SRR) and a complementary resonator with detachable rings (CSRR). The possibility of using the studied antennas in 5G, Wi-Fi standards (2.4 GHz, 5 GHz, 6E standard) is considered, the advantages of using both metamaterials and fractal geometries to increase energy efficiency and noise immunity of digital communication systems are shown.
Comparison of Double Balloon Catheter and Dinoprostone Vaginal Insert in Induced Labor: A Meta-Analysis of 2267 Patients
Authors: Zhou Xiaomeng , Wang Yun
Published: February 2025

Background: Labor induction is a common procedure in obstetrics, with various methods employed to facilitate the process. This study aimed to compare the effects of labor induction using the double-balloon catheter (DBC) and dinoprostone (D), two widely used methods in clinical practice. Methods: Randomized controlled trials (RCTs) were identified from the Cochrane Library, SinoMed, PUBMED, and Embase up to March 2024. Two researchers independently screened and extracted the literature according to the inclusion and exclusion criteria. After evaluating the literature, Revman 5.4 software was used to analyze the data. The time to the onset of active labor and the rate of cesarean deliveries were the key outcomes. The secondary outcomes included assisted vaginal delivery, failure to progress rate, failed induction rate, incidence of nonreassuring fetal heart rate, neonatal asphyxia incidence, neonatal intensive care unit (NICU) admission rate, improvement in time to onset of active labor, time to vaginal delivery, Bishop score, need for oxytocin administration, presence of postpartum hemorrhage, vaginal delivery within 24 hours, and uterine hyperstimulation rate. Results: The total of 7 RCTs involving 2267 patients were included, with 1127 treated with DBC, and 1140 treated with D. Our meta-analysis showed no significant difference between the two groups in terms of cesarean delivery [odds ratio (OR) = 1.10, 95% confidence interval (95% CI): 0.91, 1.32, p = 0.34], time to onset of active labor [mean difference (MD) = 0.66, 95% CI: –4.72, 6.03, p = 0.81], presence of nonreasuring fetal heart, success rate of induction, improvement in Bishop score, rate of progress in labor, vaginal delivery rate within 24 hours, time to vaginal delivery, postpartum hemorrhage, and assisted vaginal delivery. Although the oxytocin administration rate (OR = 3.96, 95% CI: 3.18, 4.93, p < 0.00001) was lower, D was more likely to cause uterine hyperstimulation, leading to a higher rate of neonatal asphyxia (OR = 0.39, 95% CI: 0.18, 0.85, p = 0.02). Conclusions: Compared to DBC, D was more likely to cause uterine hyperstimulation, leading to a higher rate of neonatal asphyxia.
Oxidative Stress in Pediatric Asthma: Sources, Mechanisms, and Therapeutic Potential of Antioxidants
Authors: Han Yanhua , Zhang Mingyao , Yu Shishu , Jia Lulu
Published: February 2025

Pediatric asthma is a common respiratory condition in children, characterized by a complex interplay of environmental and genetic factors. Evidence shows that the airways of stimulated asthmatic patients have increased oxidative stress, but the exact mechanisms through which this stress contributes to asthma progression are not fully understood. Oxidative stress originates from inflammatory cells in the airways, producing significant amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS). External factors such as cigarette smoke, particulate matter, and atmospheric pollutants also contribute to ROS and RNS levels. The accumulation of these reactive species disrupts the cellular redox balance, leading to heightened oxidative stress, which activates cellular signaling pathways and modulates the release of inflammatory factors, worsening asthma inflammation. Therefore, understanding the sources and impacts of oxidative stress in pediatric asthma is crucial to developing antioxidant-based treatments. This review examines the sources of oxidative stress in children with asthma, the role of oxidative stress in asthma development, and the potential of antioxidants as a therapeutic strategy for pediatric asthma.
Bacteria- and Phage-Derived Proteins in Phage Infection
Authors: Guliy Olga I. , Evstigneeva Stella S.
Published: February 2025

Phages have exerted severe evolutionary pressure on prokaryotes over billions of years, resulting in major rearrangements. Without every enzyme involved in the phage–bacterium interaction being examined; bacteriophages cannot be used in practical applications. Numerous studies conducted in the past few years have uncovered a huge variety of bacterial antiphage defense systems; nevertheless, the mechanisms of most of these systems are not fully understood. Understanding the interactions between bacteriophage and bacterial proteins is important for efficient host cell infection. Phage proteins involved in these bacteriophage–host interactions often arise immediately after infection. Here, we review the main groups of phage enzymes involved in the first stage of viral infection and responsible for the degradation of the bacterial membrane. These include polysaccharide depolymerases (endosialidases, endorhamnosidases, alginate lyases, and hyaluronate lyases), and peptidoglycan hydrolases (ectolysins and endolysins). Host target proteins are inhibited, activated, or functionally redirected by the phage protein. These interactions determine the phage infection of bacteria. Proteins of interest are holins, endolysins, and spanins, which are responsible for the release of progeny during the phage lytic cycle. This review describes the main bacterial and phage enzymes involved in phage infection and analyzes the therapeutic potential of bacteriophage-derived proteins.
Current Topics in Dental Follicle Cell Research
Authors: Morsczeck Christian
Published: February 2025

Dental follicle cells (DFCs) are dental stem cells that can only be obtained from tooth germs or after extraction of unerupted wisdom teeth. For many years, DFCs have been studied in basic research and preclinical studies in regenerative dentistry, as they are involved in both the development of the periodontium and tooth eruption. Since the first isolation, the number of studies with DFCs has increased. This article summarizes the most important articles of the last five years to provide an overview of current research topics. The focus was on basic research and preclinical research. Basic research includes articles on tooth development and tooth eruption, as well as research into molecular mechanisms during osteogenic differentiation. In addition, articles on preclinical research with DFCs focused on regenerative therapies and immunotherapies are also discussed. These new studies show that DFCs have improved our understanding of periodontal development and regeneration. DFC research is important for the regenerative dentistry of the future; however, preclinical studies indicate that significant progress is still needed before DFCs can be integrated into routine clinical practice.
The Role of HMGB1 in Infection-Related Cognitive Deficits
Authors: Irzan Fathima Ijaza , Retinasamy Thaarvena , Wen Wong Ruo , Sheng Edward Ting Ming , Shaikh Mohd. Farooq , Arulsamy Alina
Published: February 2025

Infectious diseases caused by fungi, viruses, or bacteria can have a profound impact on human cognition. This can be due to either direct spread to the central nervous system (CNS) or indirect neuroinflammation. Ultimately causing neuronal damage and even neurodegeneration. Deteriorations in cognition, such as poor encoding and attention deficits, have been reported secondary to infectious diseases. Preclinical studies have identified the underlying mechanisms of these infection-related cognitive effects, such as through blood-brain barrier (BBB) disruption and M1 microglial polarization. These mechanisms are spearheaded by inflammatory markers that are released/initiated by the pathogens over the course of the infection. Among them, the high mobility group box 1 (HMGB1) protein is a common biomarker implicated across several infection-related cognitive deficits. Understanding these effects and mechanisms is crucial for the development of strategies to prevent and treat infection-related cognitive impairment. This review will thus consolidate and elucidate the current knowledge on the potential role of HMGB1 as a therapeutic target for infection-related cognitive impairments. This review will not only advance scientific understanding but also have significant clinical and public health implications, especially considering recent global health challenges. Based on the selected articles, extracellular HMGB1, as opposed to intracellular HMGB1, acts as damage-associated molecular patterns (DAMPs) or alarmins when released in the peripheries secondary to inflammasome activation. Due to their low molecular weight, they then enter the CNS through routes such as retrograde transport along the afferent nerves, or simple diffusion across the impaired BBB. This results in further disruption of the brain microenvironment due to the dysregulation of other regulatory pathways. The outcome is structural neuronal changes and cognitive impairment. Given its key role in neuroinflammation, HMGB1 holds promise as both a biomarker for diagnostic detection and a potential therapeutic target candidate for preventing infection-related cognitive impairment.
From Pathophysiology to Treatment: The Role of Ferroptosis in PCOS
Authors: An Jie , Zhou Qin , Guo Xiaojing , Xu Congya , Jia XiaoFang , Cao Zhenzhen , Lu Qibin
Published: February 2025

Polycystic ovary syndrome (PCOS) is a prevalent gynecological endocrine and metabolic disorder in women, with an incidence rate of 10–13%. The etiology of PCOS is multifaceted, involving genetic predisposition, environmental influences, lifestyle factors, and endocrine metabolic dysregulation. Iron, a critical mineral, not only plays a role in regulating female physiological functions and the progression of PCOS but also requires careful management to avoid deficiency. However, excess iron can trigger ferroptosis, a form of nonapoptotic cell death characterized by the accumulation of lipid peroxides. While numerous studies have explored ferroptosis in patients with PCOS and animal models, the precise mechanisms and therapeutic implications remain inadequately understood. This review seeks to elucidate the pathophysiology of PCOS and the contributory factors of ferroptosis. Additionally, we examine the diverse manifestations of ferroptosis in PCOS and evaluate its role. Furthermore, we introduce ferroptosis-related traditional Chinese medicines that may enhance the understanding of PCOS pathogenesis and aid in the development of targeted therapies for ferroptosis in PCOS.
Copy Number Variations of Human Ribosomal Genes in Health and Disease: Role and Causes
Authors: Veiko Natalia N. , Ershova Elizaveta S. , Kondratyeva Elena I. , Porokhovnik Lev N. , Zinchenko Rena A. , Melyanovskaya Yuliya L. , Krasovskiy Stanislav A. , Vasilyeva Tatiana P. , Kostyuk George P. , Zakharova Natalia V. , Kostyuk Svetlana V.
Published: February 2025

Background: A number of association studies have linked ribosomal DNA gene copy number (rDNA CN) to aging and pathology. Data from these studies are contradictory and depend on the quantitative method. Methods: The hybridization technique was used for rDNA quantification in human cells. We determined the rDNA CN from healthy controls (HCs) and patients with schizophrenia (SZ) or cystic fibrosis (CF) (total number of subjects N = 1124). For the first time, rDNA CN was quantified in 105 long livers (90–101 years old). In addition, we conducted a joint analysis of the data obtained in this work and previously published by our group (total, N = 3264). Results: We found increased rDNA CN in the SZ group (534 ± 108, N = 1489) and CF group (567 ± 100, N = 322) and reduced rDNA CN in patients with mild cognitive impairment (330 ± 60, N = 93) compared with the HC group (422 ± 104, N = 1360). For the SZ, CF, and HC groups, there was a decreased range of rDNA CN variation in older age subgroups compared to child subgroups. For 311 patients with SZ or CF, rDNA CN was determined two or three times, with an interval of months to several years. Only 1.2% of patients demonstrated a decrease in rDNA CN over time. We did not find significant rDNA CN variation in eight different organs of the same patient or in cells of the same fibroblast population. Conclusions: The results suggest that rDNA CN is a relatively stable quantitative genetic trait statistically associated with some diseases, which however, can change in rare cases under conditions of chronic oxidative stress. We believe that age- and disease-related differences between the groups in mean rDNA CN and its variance are caused by the biased elimination of carriers of marginal (predominantly low) rDNA CN values.
Role of Neuropeptide B/W Signaling in Modulating Intracellular Calcium in Human Skin Fibroblasts
Authors: Pandey Shashank , Peroni Elisa , Jarkovska Dagmar , Chottova Dvorakova Magdalena , Monasson Olivier , Jirasko Michal , Chmelir Tomas , Kučera Radek
Published: February 2025

Background: The neuropeptide B/W signalling system (NPB/W) has been identified in multiple body regions and is integral to several physiological processes, including the regulation of food intake and energy homeostasis. Recently, it has also been detected in human skin; however, its specific functions in this context remain to be thoroughly investigated. This study aims to identify the expression of neuropeptides B/W receptor 1 (NPBWR1) and neuropeptides B/W receptor 2 (NPBWR2) in human dermal fibroblasts of mesenchymal origin using genomic and proteomic techniques. We will also investigate the role of these receptors in cell proliferation and calcium signalling. Methods: The mRNAs for NPBWR1 and NPBWR2 were detected using quantitative PCR (qPCR) analysis and further validated by western blot and immunofluorescence analyses. Additionally, we synthesised ligands for these receptors, specifically hNPB (25–53) and hNPW (33–62), to investigate their effects on cell proliferation and intracellular calcium levels in human fibroblasts. Results: Our results demonstrated that hNPW (33–62) has anti-proliferative effect on human dermal fibroblasts and concentration of 0.1-μmol/L can significantly decrease intracellular calcium levels (p < 0.05). Conclusion: This finding suggests a potential role for the NPB/W signalling system in pathologies associated with impaired calcium handling, such as fibrosis. Furthermore, we observed that the proliferation of human fibroblasts was not affected by hNPB (25–53). Our findings could lead to the development of new therapeutic strategies for various skin conditions and improved wound healing.
Uncovering Sex-Related Differences in Skin Macrophage Polarization During Wound Healing in Diabetic Mice
Authors: Huang Coco X. , Siwan Elisha , Baker Callum J. , Wei Zhuoran , Shinko Diana , McGuire Helen M. , Twigg Stephen M. , Min Danqing
Published: February 2025

Background: Chronic wounds, such as diabetes-related foot ulcers, arise from delayed wound healing and create significant health and economic burdens. Macrophages regulate healing by shifting between pro- and anti-inflammatory phenotypes, known as macrophage polarization. Sex and diabetes can impair wound healing, but their influence on macrophage phenotype in skin tissue during wound healing remains unclear, which was investigated in this study using a novel two-sex diabetic mouse model. Methods: Diabetes was induced in male and female C57BL/6J mice using low-dose streptozotocin injections and high-fat diet feeding, with chow-fed mice as controls. After 18 weeks, each mouse received four circular full-thickness dorsal skin wounds. The macrophage phenotypes in wounded skin tissues at Day 0 and Day 10 post-wounding were analyzed using mass cytometry with manual gating and automated computational clustering. Results: Male diabetic mice exhibited more severe hyperglycemia and insulin resistance compared to females. Although diabetic mice did not display delayed wound healing, male mice had a greater proportion of total macrophages than females, especially a higher proportion of pro-inflammatory matrix metalloproteinase-9 (MMP-9)+ macrophages and a lower proportion of anti-inflammatory adiponectin receptor 1 (AdipoR1)+ macrophages in male diabetic mice compared to females, indicating an imbalanced polarization towards a pro-inflammatory phenotype that could result in poorer wound healing. Interestingly, computational clustering identified a new pro-inflammatory, pro-healing phenotype (Ly6C+AdipoR1+CD163–CD206–) more abundant in females than males, suggesting this phenotype may play a role in the transition from the inflammatory to the proliferative stage of wound healing. Conclusions: This study demonstrated a significant sex-based difference in macrophage populations, with male diabetic mice showing a pro-inflammatory bias that may impair wound healing, while a unique pro-inflammatory, pro-healing macrophage population more abundant in females could facilitate recovery. Further research is needed to investigate the role of these newly identified phenotypes in regulating impaired wound healing.
Polarized Tissue-Derived Macrophages Display Enhanced M2d Phenotype after Prolonged Stimulation with Adenosine A2A Receptor Agonist in the Presence of LPS
Authors: Barilo Julia , Ratsimor Mariane , Chan Agnes , Hembruff Hannah , Basta Sam
Published: February 2025

Background: Macrophages (Mφ) are innate immune cells known for their different activation phenotypes, classically described as falling within two broad categories, M1 and M2. The latter were originally described as alternatively activated M2 cells to differentiate them from classically activated M1 cells. M2 cells were later classified into M2a (interleukin (IL)-4), M2b (immune complex), M2c (IL-10) and M2d (5-(N-ethylcarboxamido) adenosine (NECA) + lipopolysaccharide (LPS)) based on their inducing stimuli. Considering the established role of M2d/tumour-associated macrophage (TAM) cells within cancer initiation and proliferation, expanding on the knowledge of M2d characteristics can provide fundamental information for Mφ targeted immunotherapy. The precise characterization of M2d cells derived from tissues has not been described in detail. Methods: Our study focused on spleen-derived macrophages (SpM), which were also compared to bone marrow-derived macrophages (BMDMs). Results: By investigating different conditions for M2d-specific stimulation and employing various assays including functional tests, we show how Mφ M2d (NECA + LPS) polarization can be affected by prolonged culture conditions to induce a phenotype that was clearly different from M2a cells. Conclusion: This work offers new insights into the properties of primary M2d Mφ following extended stimulation with LPS and NECA.
Immune Imbalance in Primary Membranous Nephropathy at Single-cell Resolution
Authors: Tie Xuan , Chen Zhiang , Yao Shulei , Wu Binxin , Yan Bingjuan , Zhai Huifang , Qiao Xi , Su Xiaole , Wang Lihua
Published: February 2025

Background: Primary membranous nephropathy (pMN) often progresses to end-stage renal disease (ESRD) in the absence of immunosuppressive therapy. The immunological mechanisms driving pMN progression remain insufficiently understood. Methods: We developed a single-cell transcriptomic profile of peripheral blood mononuclear cells (PBMCs) from 11 newly-diagnosed pMN patients and 5 healthy donors. Through correlation analysis, we identified potential biomarkers for disease stratification and poor prognosis. Results: Expression levels of several proinflammatory factors were significantly increased in patients compared to healthy donors, such as interleukins (IL1B, IL8, and IL15) and interferon G (IFNG). Multiple pattern recognition receptors involved in proinflammatory signaling were also upregulated in patients, including NOD-like receptors (NLRs) (NLRP1, NLRP3, and NLRC5), RNA helicases (DDX58, IFIH1, DHX9, and DHX36), cGAS (cyclic GMP-AMP synthase) and IFI16 (interferon gamma inducible protein 16). Additionally, human leukocyte antigen molecules HLA-DQA1 and HLA-DRB1 enriched in memory B cells were upregulated in patients. More importantly, we found that the genes for antiviral defense response were significantly elevated in high-risk patients relative to the low-risk group. More than twenty genes were negatively correlated with estimated glomerular filtration rate (eGFR), such as BST2 (bone marrow stromal cell antigen 2) and SLC35F1 (solute carrier family 35 member F1). Their predicted values were confirmed in a larger population with nephrotic syndrome or other chronic kidney diseases from a public database. Furthermore, we developed a series of scoring systems for distinguishing high-risk patients from low- and moderate-risk individuals. Conclusions: Our study provides insight into the immunological mechanism of pMN and identifies numerous biomarkers and signaling pathways as potential therapeutic targets for managing the progression of high-risk pMN.
The Role of Microglia in Perioperative Pain and Pain Treatment: Recent Advances in Research
Authors: Shi Shengnan , Gong Xingrui
Published: February 2025

Microglia play a crucial role in monitoring the microenvironment of the central nervous system. Over the past decade, the role of microglia in the field of pain has gradually been unraveled. Microglia activation not only releases proinflammatory factors that enhance nociceptive signaling, but also participates in the resolving of pain. Opioids induce microglia activation, which enhances phagocytic activity and release of neurotoxic substances. Conversely, microglia activation reduces opioid efficacy and results in opioid tolerance. The application of microglia research to clinical pain management and drug development is a promising but challenging area. Microglia-targeted therapies may provide new avenues for pain management.
Research Progress in the Pathogenesis of Cognitive Dysfunction in White Matter Hyperintensities: A Narrative Review
Authors: Song Ni-Na , Yu Jing-Yuan , Wang Chao , Wu Xue-Qi , Ma Guo-Zhao , Yuan Xiao-Ying , Wang Xu-Gang
Published: February 2025

Cerebral small vessel disease is a common disease endangering human health due to its insidious and repeated onset and progressive aggravation. White matter hyperintensities (WMHs) are one of the classic imaging markers of cerebral small vessel disease. The term ‘WMHs’ was first proposed by Hachinski in 1987. The WMHs in our study mainly refer to cerebral white matter damage caused by various vascular factors, known as vascularized white matter hyperintensity. WMHs are significantly correlated with stroke, cognitive dysfunction, emotional disturbance, and gait abnormality, and have drawn widespread attention. This article reviews the research progress on the pathogenesis of cognitive dysfunction associated with WMHs and provides a theoretical reference for understanding the pathogenesis of WMHs and the early assessment of associated cognitive dysfunction.
Prolonged Chronic Cerebral Hypoperfusion Does not Exacerbate Tau Pathology in a Tauopathy Mouse Model
Authors: Lee Na Kyung , Na Duk L. , Kim Hee Jin , Jang Hyemin , Sa Jason K. , Ko Bae Sung , Chang Jong Wook
Published: February 2025

Background: Several preclinical studies have reported elevated levels of tau following the induction of chronic cerebral hypoperfusion (CCH) in Alzheimer’s disease mouse models. The objective of this study was to first induce CCH in a mouse model of tauopathy over an extended period of up to 6 months and to subsequently investigate the effects of CCH on tau accumulation and alterations in the transcriptome. Methods: Three-month-old P301S tauopathy mice were randomly allocated to either a Sham or CCH group. The common carotid arteries (CCAs) of the CCH group were bilaterally implanted using 0.75-mm inner diameter ameroid constrictors. Prior to surgery, Doppler ultrasound imaging was acquired, with follow-up imaging at 1, 3, and 6 months postoperatively. Brain tissue samples were obtained, and hemispheres were dissected and divided for separate analysis. Result: No significant differences in phosphorylated and total tau protein levels were found in either Sham or CCH left cortical hemispheres or hippocampal lysates. Immunohistochemical staining of phosphorylated tau in the right hemisphere revealed similar findings. Compared with the Sham group, transcriptomic deconvolution revealed a significant reduction of memory B cells in the CCH group (p = 0.029). Conclusion: To clarify the effects of chronic hypoperfusion on tau pathology, more than one surgical method of hypoperfusion should be used in future studies.
Resting-State Brain Network Characteristics Related to Mild Cognitive Impairment: A Preliminary fNIRS Proof-of-Concept Study
Authors: Yang Guohui , Fan Chenyu , Li Haozheng , Tong Yu , Lin Shuang , Feng Yashuo , Liu Fengzhi , Bao Chunrong , Xie Hongyu , Wu Yi
Published: February 2025

Background: This study investigates the reliability of functional near-infrared spectroscopy (fNIRS) in detecting resting-state brain network characteristics in patients with mild cognitive impairment (MCI), focusing on static resting-state functional connectivity (sRSFC) and dynamic resting-state functional connectivity (dRSFC) patterns in MCI patients and healthy controls (HCs) without cognitive impairment. Methods: A total of 89 MCI patients and 83 HCs were characterized using neuropsychological scales. Subject sRSFC strength and dRSFC variability coefficients were evaluated via fNIRS. The study evaluated the feasibility of using fNIRS to measure these connectivity metrics and compared resting-state brain network characteristics between the two groups. Correlations with Montreal Cognitive Assessment (MoCA) scores were also explored. Results: sRSFC strength in homologous brain networks was significantly lower than in heterologous networks (p < 0.05). A significant negative correlation was also observed between sRSFC strength and dRSFC variability at both the group and individual levels (p < 0.001). While sRSFC strength did not differentiate between MCI patients and HCs, the dRSFC variability between the dorsal attention network (DAN) and default mode network (DMN), and between the ventral attention network (VAN) and visual network (VIS), emerged as sensitive biomarkers after false discovery rate correction (p < 0.05). No significant correlation was found between MoCA scores and connectivity measures. Conclusions: fNIRS can be used to study resting-state brain networks, with dRSFC variability being more sensitive than sRSFC strength for discriminating between MCI patients and HCs. The DAN-DMN and VAN-VIS regions were found to be particularly useful for the identification of dRSFC differences between the two groups. Clinical Trial Registration: ChiCTR2200057281, registered on 6 March, 2022; https://www.chictr.org.cn/showproj.html?proj=133808.
Prognostic Significance of Homocysteine Levels in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Propensity Score Matching and Weighting Analysis
Authors: Xiong Qianfeng , Chen Shaoyong , Luo Junke , Xiong Pengfeng , Nie Zhenyun , Huang Lei , Wang Yao , Lei Zhen , Zhang Lihui , Wang Jing
Published: February 2025

Background: Elevated homocysteine (Hcy) levels have been linked to poorer outcomes in acute coronary syndrome. This study aimed to assess the predictive value of elevated Hcy levels for major adverse cardiac events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: This retrospective cohort study included 183 STEMI patients who underwent primary PCI at a tertiary university hospital in southern China from January 2020 to December 2021. Laboratory values, including Hcy levels, were obtained within 24 hours of admission. Patients were categorized into elevated and normal Hcy groups using a threshold of 12 μmol/L. The study outcome was the occurrence of 6-point MACE, defined as cardiac death, nonfatal myocardial infarction, stroke, ischemia-driven revascularization (PCI or coronary artery bypass grafting), heart failure and all-cause death. Survival analyses were conducted using Kaplan-Meier and Cox proportional hazard methods. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) approaches were employed to minimize bias. Results: The mean age of the patients was 64.8 years, with 76.0% being male. After adjusting with PSM or IPTW, covariate imbalances between the two groups were corrected. Over a median follow-up period of 25.8 months, 55 MACE events occurred, resulting in an event rate of 30.1%. Patients with elevated Hcy levels had a higher incidence of MACE in both unadjusted (hazard ratio [HR] = 2.778; 95% confidence interval [CI]: 1.591–4.850; p < 0.001) and adjusted analyses (PSM: HR = 2.995; 95% CI: 1.397–6.423, p = 0.005; IPTW: HR = 3.2; 95% CI: 1.631–6.280, p < 0.001). Multivariate Cox regression further confirmed that elevated Hcy levels were associated with a worse prognosis across the entire cohort (HR = 1.062, 95% CI: 1.029–1.097, p < 0.001), PSM cohort (HR = 1.089, 95% CI: 1.036–1.145, p < 0.001), and IPTW cohort (HR = 1.052, 95% CI: 1.020–1.086, p = 0.001). Conclusions: Elevated plasma levels of Hcy (≥12 μmol/L) are associated with worse outcomes in STEMI patients undergoing primary PCI, highlighting the potential role of Hcy as a prognostic marker in this population.
Early Predictive Value of Infectious Markers for Ventilator-associated Pneumonia after Stanford Type A Aortic Dissection Surgery
Authors: Deng Huibiao , Wu Xiaohong , Peng Bo
Published: February 2025

Background: This study investigates the early predictive value of infectious markers for ventilator-associated pneumonia (VAP) after Stanford type A aortic dissection surgery. Methods: A retrospective review of the medical records of all patients with Stanford type A aortic dissection admitted to Shanghai General Hospital from July 2020 to July 2023 who received mechanical ventilation after surgery was performed. Patients were divided into infection and non-infection groups according to the presence of VAP. The clinical data of the two groups were compared. The early predictive values of procalcitonin (PCT), C-reactive protein (CRP), the neutrophil/lymphocyte ratio (NLR) and sputum smears for VAP were evaluated by receiver operating characteristic (ROC) curve analysis. Results: A total of 139 patients with Stanford type A aortic dissection were included in this study. There were 35 cases of VAP infection, and the VAP incidence rate was 25.18%. The CRP, PCT, and NLR levels in the infection group were more significant than those in the non-infection group (p < 0.05). The percentage of positive sputum smears was 80.00% in the infected group and 77.88% in the non-infected group. The ROC curve analysis revealed that the areas under the curve (AUCs) of PCT, the NLR, CRP and sputum smear were 0.835, 0.763, 0.820 and 0.745, respectively, and the AUC for the combined diagnosis was 0.923. The pathogenic bacteria associated with VAP, after Stanford type A aortic dissection, was mainly gram-negative bacteria. Conclusions: The combined application of the NLR, CRP, PCT and sputum smear is helpful for the early diagnosis of VAP after Stanford type A aortic dissection surgery to help clinicians make decisions about treating VAP quickly.
CCL11 (Eotaxin) Promotes the Advancement of Aging-Related Cardiovascular Diseases
Authors: Zhang Tanwei , Huang Yanhong , Ji Xinmeng , Wu Teng , Xiao Pingxi
Published: February 2025

Aging-related diseases, such as cardiovascular diseases (CVDs), neurodegeneration, cancer, etc., have become important factors that threaten the lifespans of older individuals. A chronic inflammatory response is closely related to aging-related diseases. Establishing inflammatory aging clock (iAGE, deep-learning methods on blood immune biomarkers to construct a metric for age-related chronic inflammation) successfully predicted the positive correlation between several factors, including serum C–C-motif chemokine ligand 11 (CCL11) and aging-related diseases. Recently, the role and mechanism of CCL11, an eosinophilic chemokine, in neurodegenerative diseases have been widely reported. Additionally, many research studies have shown a positive correlation with CVDs, but the underlying mechanism remains unknown. This review focuses on the relationship between chronic inflammation and aging. The role of CCL11 will be discussed and summarized in relation to aging-related diseases, especially CVDs.