bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled Extended Branciari Quasi-b-Metric Spaces, Results, and Applications to Riesz-Caputo Fractional Differential Equations and Nonlinear Matrix Equations
Authors: Jain Reena , Nashine Hemant Kumar , George Reny
Published: December 2023

We introduce the concept of controlled extended Branciari quasi-b-metric spaces, as well as a Gq-implicit type mapping. Under this new space setting, we derive some new fixed points, periodic points, right and left Ulam–Hyers stability, right and left weak well-posed properties, and right and left weak limit shadowing results. Additionally, we use these findings to solve the fractional differential equations of a Riesz–Caputo type with integral anti-periodic boundary values, as well of nonlinear matrix equations. All ideas, results, and applications are properly illustrated with examples.
Finite-Approximate Controllability of ν-Caputo Fractional Systems
Authors: Awadalla Muath , Mahmudov Nazim I. , Alahmadi Jihan
Published: December 2023

This paper introduces a methodology for examining finite-approximate controllability in Hilbert spaces for linear/semilinear ν-Caputo fractional evolution equations. A novel criterion for achieving finite-approximate controllability in linear ν-Caputo fractional evolution equations is established, utilizing resolvent-like operators. Additionally, we identify a control strategy that not only satisfies the approximative controllability property but also ensures exact finite-dimensional controllability. Leveraging the approximative controllability of the corresponding linear ν-Caputo fractional evolution system, we establish sufficient conditions for achieving finite-approximative controllability in the semilinear ν-Caputo fractional evolution equation. These findings extend and build upon recent advancements in this field. The paper also explores applications to ν-Caputo fractional heat equations.
Mucoadhesive Pharmacology: Latest Clinical Technology in Antiseptic Gels
Authors: Baus-Domínguez María , Aguilera Felipe-Rodrigo , Vivancos-Cuadras Fernando , Ferra-Domingo Lourdes , Torres-Lagares Daniel , Gutiérrez-Pérez José-Luis , Pereira-Riveros Tanya , Vinuesa Teresa , Serrera-Figallo María-Ángeles
Published: December 2023

Chlorhexidine (CHX) is one of the most widely used antiseptics in the oral cavity due to its high antimicrobial potential. However, many authors have stated that the effect of CHX in nonsurgical periodontal therapy is hampered by its rapid elimination from the oral environment. The aim of this study was to determine the antibacterial efficacy of a new compound of chlorhexidine 0.20% + cymenol (CYM) 0.10% on a multispecies biofilm. For this, an in vitro study was designed using a multispecies biofilm model of Streptococcus mutans, Fusobacterium nucleatum, Prevotella intermedia, and Porphyromonas gingivalis. Quantification of the microbial viability of the biofilm was performed using 5-cyano-2,3-ditolyl tetrazolium-chloride (CTC) to calculate the percentage of survival, and the biofilms were observed using a a confocal laser scanning microscopy (CLSM). It was observed that the bactericidal activity of the CHX + cymenol bioadhesive gel was superior to that of the CHX bioadhesive gel, in addition to higher penetrability into the biofilm. Therefore, there was greater elimination of bacterial biofilm with the new compound of chlorhexidine 0.2% plus cymenol 0.1% in a bioadhesive gel form compared to the formulation with only chlorhexidine 0.2% in a bioadhesive gel form.
Notes toward a Demographic History of the Jews
Authors: DellaPergola Sergio
Published: December 2023

As an essential prerequisite to the genealogical study of Jews, some elements of Jewish demographic history are provided in a long-term transnational perspective. Data and estimates from a vast array of sources are combined to draw a profile of Jewish populations globally, noting changes in geographical distribution, vital processes (marriages, births and deaths), international migrations, and changes in Jewish identification. Jews often anticipated the transition from higher to lower levels of mortality and fertility, or else joined large-scale migration flows that reflected shifting constraints and opportunities locally and globally. Cultural drivers typical of the Jewish minority interacted with socioeconomic and political drivers coming from the encompassing majority. The main centers of Jewish presence globally repeatedly shifted, entailing the intake within Jewish communities of demographic patterns from significantly different environments. During the 20th century, two main events reshaped the demography of the Jews globally: the Shoah (destruction) of two thirds of all Jews in Europe during World War II, and the independence of the State of Israel in 1948. Mass immigration and significant convergence followed among Jews of different geographical origins. Israel’s Jewish population grew to constitute a large share—and in the longer run—a potential majority of all Jews worldwide. Since the 19th century, and with increasing visibility during the 20th and the 21st, Jews also tended to assimilate in the respective Diaspora environments, leading to a blurring of identificational boundaries and sometimes to a numerical erosion of the Jewish population. This article concludes with some implications for Jewish genealogical studies, stressing the need for contextualization to enhance their value for personal memory and for analytic work.
Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations
Authors: Izhar Raafiah , Borriello Margherita , La Russa Antonella , Di Paola Rossella , De Ananya , Capasso Giovambattista , Ingrosso Diego , Perna Alessandra , Simeoni Mariadelina
Published: December 2023

Fabry Disease (FD) is a rare lysosomal storage disorder caused by mutations in the GLA gene on the X chromosome, leading to a deficiency in α-galactosidase A (AGAL) enzyme activity. This leads to the accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3), in vital organs such as the kidneys, heart, and nervous system. While FD was initially considered predominantly affecting males, recent studies have uncovered that heterozygous Fabry women, carrying a single mutated GLA gene, can manifest a wide array of clinical symptoms, challenging the notion of asymptomatic carriers. The mechanisms underlying the diverse clinical manifestations in females remain not fully understood due to X-chromosome inactivation (XCI). XCI also known as “lyonization”, involves the random inactivation of one of the two X chromosomes. This process is considered a potential factor influencing phenotypic variation. This review delves into the complex landscape of FD in women, discussing its genetic basis, the available biomarkers, clinical manifestations, and the potential impact of XCI on disease severity. Additionally, it highlights the challenges faced by heterozygous Fabry women, both in terms of their disease burden and interactions with healthcare professionals. Current treatment options, including enzyme replacement therapy, are discussed, along with the need for healthcare providers to be well-informed about FD in women, ultimately contributing to improved patient care and quality of life.
Genome-Wide Identification of Trehalose-6-phosphate Synthase (TPS) Gene Family Reveals the Potential Role in Carbohydrate Metabolism in Peach
Authors: Fan Shihao , Wang Zhe , Xiao Yuansong , Liang Jiahui , Zhao Shilong , Liu Yihua , Peng Futian , Guo Jian
Published: December 2023

Trehalose-6-phosphate synthase (TPS) is essential for plant growth and development, linking trehalose-6-phosphate (T6P) to carbon metabolism. However, little is known about the TPS gene family in peaches and their potential roles in regulating carbohydrates in peach fruit. In this study, nine TPS genes were identified in the peach genome and named according to the homologous genes in Arabidopsis. Phylogenetic analysis showed that three subfamilies were identified, including TPSI, TPSII-1, and TPSII-2, which were also consistent with gene structure analysis. Considerable cis-elements were enriched in the promoters, including plant hormone-related elements. Tissue-specific analysis showed that these TPS genes were mainly expressed in leaves, stems, and fruit, showing different expression patterns for each gene. In addition, during fruit development, the content of trehalose-6-phosphate (T6P) was positively correlated with the expression of PpTPS7a and negatively with sucrose non-fermenting-1-related kinase 1 (SnRK1) activity. Transient overexpression and silencing of PpTPS7a in peach fruit validated its function in regulating T6P content and SnRK1 activity.
Dynamic Expression Profile of Follicles at Different Stages in High- and Low-Production Laying Hens
Authors: Yang Lan , Fan Xuewei , Tian Kaiyuan , Yan Sensen , Xu Chunhong , Tian Yixiang , Xiao Chengpeng , Jia Xintao , Shi Junlai , Bai Ying , Li Wenting
Published: December 2023

Improving the efficiency of hens and extending the egg-laying cycle require maintaining high egg production in the later stages. The ovarian follicles, as the primary functional units for ovarian development and oocyte maturation, play a crucial role in regulating the continuous ovulation of hens. The egg production rate of laying hens is mostly affected by proper follicle growth and ovulation in the ovaries. The objective of this study was to identify the key genes and signaling pathways involved in the development of ovarian follicles in Taihang hens through transcriptome screening. In this study, RNA sequencing was used to compare and analyze the transcriptomes of ovarian follicles at four developmental stages: small white follicles (SWF), small yellow follicles (SYF), F5 follicles, and F2 follicles, from two groups: the high continual production group (H-Group) and the low continual production group (L-Group). A total of 24 cDNA libraries were constructed, and significant differential expression of 96, 199, 591, and 314 mRNAs was detected in the SWF, SYF, F5, and F2 follicles of the H and L groups, respectively. Based on the results of GO and KEGG enrichment analyses, each stage of follicle growth possesses distinct molecular genetic features, which have important effects on follicle development and significantly promote the formation of continuous production traits through the biosynthesis of steroid hormones, cytokine–cytokine receptor interaction, and neuroactive ligand–receptor interaction. Additionally, through STEM analysis, we identified 59 DEGs, including ZP4, KCNH1, IGFs, HMGA2, and CDH1, potentially associated with follicular development within four significant modules. This study represents the first transcriptome investigation of follicles in hens with high and low egg-producing characteristics at four crucial developmental stages. These findings provide important molecular evidence for understanding the regulation of follicular development and its variations.
QTL Mapping of Trichome Traits and Analysis of Candidate Genes in Leaves of Wheat (Triticum aestivum L.)
Authors: Fan Hua , Xu Jianchao , Ao Dan , Jia Tianxiang , Shi Yugang , Li Ning , Jing Ruilian , Sun Daizhen
Published: December 2023

Trichome plays an important role in heat dissipation, cold resistance, water absorption, protection of leaves from mechanical damage, and direct exposure to ultraviolet rays. It also plays an important role in the photosynthesis, transpiration, and respiration of plants. However, the genetic basis of trichome traits is not fully understood in wheat. In this study, wheat DH population (Hanxuan 10 × Lumai 14) was used to map quantitative trait loci (QTL) for trichome traits in different parts of flag leaf at 10 days after anther with growing in Zhao County, Hebei Province, and Taigu County, Shanxi Province, respectively. The results showed that trichome density (TD) was leaf center > leaf tip > leaf base and near vein > middle > edge, respectively, in both environments. The trichome length (TL) was leaf tip > leaf center > leaf base and edge > middle > near vein. Significant phenotypic positive correlations were observed between the trichome-related traits of different parts. A total of 83 QTLs for trichome-related traits were mapped onto 18 chromosomes, and each one accounted for 2.41 to 27.99% of the phenotypic variations. Two QTL hotspots were detected in two marker intervals: AX-95232910~AX-95658735 on 3A and AX-94850949~AX-109507404 on 7D. Six possible candidate genes (TraesCS3A02G406000, TraesCS3A02G414900, TraesCS3A02G440900, TraesCS7D02G145200, TraesCS7D02G149200, and TraesCS7D02G152400) for trichome-related traits of wheat leaves were screened out according to their predicted expression levels in wheat leaves. The expression of these genes may be induced by a variety of abiotic stresses. The results provide the basis for further validation and functional characterization of the candidate genes.
Group Belonging and Social Identities in the Transition of Asylum-Seekers in Greece: Longitudinal Pathways to Adjustment
Authors: Panagiotopoulos Angelos , Pavlopoulos Vassilis
Published: December 2023

Millions of forced migrants settling in host countries often struggle to adjust to their new life. As their inclusion and adjustment within receiving societies has become a global social challenge, studying the factors that support their successful transition is an important topic of research inquiry. The present three-wave longitudinal study examined the role of group belonging and social identification in facilitating the transition of 60 sub-Saharan African asylum-seekers to Greece. Drawing upon the Social Identity Model of Identity Change (SIMIC), we investigated how multiple group memberships before migration, social identity continuity, and social identity gain related to their adjustment over 8 months. On the between-person level, multiple group belonging before migration indirectly contributed to better person-average levels of sociocultural adjustment, physical health functioning and satisfaction, psychological distress, and life satisfaction, by way of higher person-average levels of social identity continuity and/or social identity gain. However, multiple groups before migration also had a direct negative effect on the overall levels of psychological distress. On the within-person level, positive changes in social identity continuity and gain were related to positive changes in different adjustment-related outcomes over time. Our findings are consistent with SIMIC and highlight the importance of group belonging and associated social identities in forced migrants’ transition, in ways that may pave the way for the development of social identity interventions to promote their health, well-being, and successful integration. Future longitudinal and experimental evidence with larger and more diverse samples of forced migrants is needed to establish the generalizability and causality of the observed associations.
Current Research Status and Implication for Further Study of Real-World Data on East Asian Traditional Medicine for Heart Failure: A Scoping Review
Authors: Park Jeongsu , Bak Seongjun , Chu Hongmin , Kang Sukjong , Youn Inae , Jun Hyungsun , Sim Daeun , Leem Jungtae
Published: December 2023

This study used real-world data (RWD) to explore the long-term effects of East Asian traditional medicine (EATM) on heart failure (HF). A comprehensive search was conducted across five databases to identify relevant studies, which were then reviewed using the Arksey and O’Malley scoping review framework. The analysis focused on a descriptive examination of the long-term outcomes associated with EATM intervention. Methodologically, the study explored various aspects, including study subjects, interventions, applied clinical outcomes, and statistical methods. Out of 258 studies, 12 were selected. Eight studies involved patients with HF, while the others used HF as an outcome. Datasets from the National Health Insurance Research Database were used in Taiwan, while electronic medical record data were used in China and Japan. EATM interventions have been found to be associated with lower mortality and readmission rates. One study indicated that an increased dose of Fuzi, a botanical drug, or prompt use of Fuzi after diagnosis led to a decreased mortality hazard ratio. In two studies examining readmission rates, a significant increase was observed in the non-exposed group, with odds ratios of 1.28 and 1.18. Additionally, in patients with breast cancer, the subdistribution hazard ratio for the occurrence of doxorubicin-induced HF was reduced to 0.69. Although cohort studies with survival analysis were common, methodological flaws, such as issues with statistical methods and HF diagnosis, were identified. Despite these challenges, the study observed an association between EATM and improved clinical outcomes in patients with HF, emphasizing the potential of RWD studies to complement randomized controlled trials, especially for longer-term follow-ups. These results provide foundational data for future RWD research.
Qualitative Analysis of Conversational Chatbots to Alleviate Loneliness in Older Adults as a Strategy for Emotional Health
Authors: Rodríguez-Martínez Antonia , Amezcua-Aguilar Teresa , Cortés-Moreno Javier , Jiménez-Delgado Juan José
Published: December 2023

This article presents an exploration of conversational chatbots designed to alleviate loneliness among older adults. In addition to technical evaluation, it delves into effective communication between these systems and this demographic group, considering linguistic nuances, communicative preferences, and specific emotional needs. The intrinsic importance of chatbots as innovative solutions in combating loneliness is highlighted, emphasizing their ability to be understanding and empathetic allies, contributing to emotional well-being and socialization. The article explores how improved emotional well-being can positively impact the health and quality of life of older adults. The methodology, rooted in triangulation between a literature review and qualitative research through interviews and focus groups with older adults, provides a comprehensive insight into the findings. Ethical, technical, and design considerations such as privacy, autonomy, technology adaptation, and usability are also addressed. The article concludes with practical recommendations for developing user-friendly interfaces that encourage the active participation of older adults in chatbots. This holistic approach not only analyzes the technical effectiveness of chatbots in mitigating loneliness in older adults but delves into human, ethical, and practical aspects, enriching the understanding and implementation of these agents for social and emotional support.
Silver Nanoparticles and Biostimulants Affect Chemical Constituents, Total Phenolics, Antioxidants, and Potential Antimicrobial Activities of Santolina chamaecyparissus
Authors: Al-Ramamneh Ezz Al-Dein , Alsharafa Khalid Y. , Rababah Taha , Rahahleh Razan J. , Al-Rimawi Fuad , Shakya Ashok K. , Ghrair Ayoup M. , Alu’datt Muhammad H. , Alnawafleh Moayad K.
Published: December 2023

The beneficial application of silver nanoparticles and biostimulants to increase crop yield and quality is a long-term strategy to achieve desired agricultural productions that are resilient to various biotic and abiotic challenges. This project aimed to evaluate the individual effects of silver nanoparticles (AgNPs), Ascophyllum nodosum (SEW), and Spirulina platensis (SP) on the growth and physiological responses of Santolina chamaecyparissus. S. chamaecyparissus plants were exposed to AgNPs (20, 40, and 60 mg L−1), SWE (0.5% and 1%), and SP (1%, 2%, and 3%). The finding indicates that the light-harvesting efficiency and plant photochemical capacity are not affected by most treatments except for 60 mg L−1 AgNPs. Furthermore, the pattern of H2O2 levels in leaves was significantly higher after AgNP, SP, and SEW treatments. In parallel, total phenolic production was at least accompanied by a burst in H2O2 levels. However, higher antioxidant activity compared to the control, is shown by the higher free-DPPH-radical inhibition that goes completely smoothly with lower H2O2 levels. Thus, the results of the present study showed that biostimulants overall improved the antioxidant activity of S. chamaecyparissus and induced variable detectable amounts of phenolic compounds in response to the concentrations of each biostimulant.
Differences in Anxiety, Insomnia, and Trauma Symptoms in Wildfire Survivors from Australia, Canada, and the United States of America
Authors: Isaac Fadia , Toukhsati Samia R. , Klein Britt , Di Benedetto Mirella , Kennedy Gerard A.
Published: December 2023

Many survivors of wildfires report elevated levels of psychological distress following the trauma of wildfires. However, there is only limited research on the effects of wildfires on mental health. This study examined differences in anxiety, depression, insomnia, sleep quality, nightmares, and post-traumatic stress disorder (PTSD) symptoms following wildfires in Australia, Canada, and the United States of America (USA). One hundred and twenty-six participants from Australia, Canada, and the USA completed an online survey. The sample included 102 (81%) women, 23 (18.3%) men, and one non-binary (0.8%) individual. Participants were aged between 20 and 92 years (M age = 52 years, SD = 14.4). They completed a demographic questionnaire, the Disturbing Dream and Nightmare Severity Index (DDNSI), Generalized Anxiety Disorder Questionnaire (GAD-7), the Insomnia Severity Index (ISI), Patient Health Questionnaire (PHQ-9), the Pittsburgh Sleep Quality Index (PSQI), and PTSD Checklist (PCL-5). Results showed that participants from the USA scored significantly higher on the GAD-7 (p = 0.009), ISI (p = 0.003), and PCL-5 (p = 0.021) than participants from Australia and Canada. The current findings suggest a need for more international collaboration to reduce the severity of mental health conditions in Australia, Canada, and the USA.
Geographic Knowledge Base Question Answering over OpenStreetMap
Authors: Yang Jonghyeon , Jang Hanme , Yu Kiyun
Published: December 2023

In recent years, question answering on knowledge bases (KBQA) has emerged as a promising approach for providing unified, user-friendly access to knowledge bases. Nevertheless, existing KBQA systems struggle to answer spatial-related questions, prompting the introduction of geographic knowledge ba se question answering (GeoKBQA) to address such challenges. Current GeoKBQA systems face three primary issues: (1) the limited scale of questions, restricting the effective application of neural networks; (2) reliance on rule-based approaches dependent on predefined templates, resulting in coverage and scalability challenges; and (3) the assumption of the availability of a golden entity, limiting the practicality of GeoKBQA systems. In this work, we aim to address these three critical issues to develop a practical GeoKBQA system. We construct a large-scale, high-quality GeoKBQA dataset and link mentions in the questions to entities in OpenStreetMap using an end-to-end entity-linking method. Additionally, we develop a query generator that translates natural language questions, along with the entities predicted by entity linking into corresponding GeoSPARQL queries. To the best of our knowledge, this work presents the first purely neural-based GeoKBQA system with potential for real-world application.
A Lightweight Approach for Building User Mobility Profiles
Authors: Vallejos Sebastián , Berdun Luis , Armentano Marcelo , Schiaffino Silvia , Godoy Daniela
Published: December 2023

Data captured by mobile devices enable us, among other things, learn the places where users go, identify their home and workplace, the places they usually visit (e.g., supermarket, gym, etc.), the different paths they take to move from one place to another and even their routines. In summary, with this information, it is possible to learn a user mobility profile. In this work, we propose a lightweight approach for building mobility profiles from data collected with mobile devices. The mobility profiles of a user consist of the places visited, the visit history and the travel paths. Our approach aims to solve some of the challenges and limitations identified in the literature. Particularly, it considers geographic information to identify certain kinds of places, such as open spaces, big places and small places, that are hard to distinguish with existing approaches. We use different sensors and time frequencies to collect data in order to optimize battery consumption and maximize precision. Finally, it executes entirely on the mobile devices, avoiding the exposure of sensitive user information and then preserving user privacy. The proposal was evaluated in the context of the real usage of the developed prototype applications in two cities of Argentina. The results obtained with our approach outperformed other approaches in the literature, both in precision and recall.
Photoluminescent Layered Crystal Consisting of Anderson-Type Polyoxometalate and Surfactant toward a Potential Inorganic–Organic Hybrid Laser
Authors: Mihara Ayaka , Kojima Tatsuhiro , Suda Yoriko , Maezawa Kyoka , Sumi Toshiyuki , Mizoe Naoyuki , Watanabe Ami , Iwamatsu Hironori , Oda Yoshiki , Okamura Yosuke , Ito Takeru
Published: December 2023

The hybridization of inorganic and organic components is a promising strategy to build functional materials. Among several functions, luminescence is an important function which should be considered for practical usage. Inorganic–organic hybrid luminescent materials have been investigated as phosphors, sensors, and lasers. Organic luminescent centers such as dye molecules have often been hybridized with inorganic matrices. Polyoxometalate anions (POMs) are effective inorganic luminescent centers due to their luminescent properties and structural designability. However, most luminescent POM components are limited to lanthanide-based POMs. In this report, a photoluminescent inorganic–organic hybrid crystal based on a non-lanthanide POM was successfully synthesized as a single crystal. Anderson-type hexamolybdochromate ([CrMo6O18(OH)6]3−, CrMo6) anion exhibiting emission derived from Cr3+ was utilized with n-dodecylammonium ([C12H25NH3]+, C12NH3) surfactant cation to obtain a photoluminescent hybrid crystal. The grown single crystal of C12NH3-CrMo6 comprised a distinct layered structure consisting of inorganic CrMo6 layers and interdigitated C12NH3 layers. In the CrMo6 layers, the CrMo6 anions were associated with water molecules by hydrogen bonding to form a densely packed two-dimensional network. Steady-state and time-resolved photoluminescence spectroscopy revealed that the C12NH3-CrMo6 hybrid crystal exhibited characteristic emission from the CrMo6 anion. Preliminary lasing properties were also observed for C12NH3-CrMo6, which shows the possibility of using the C12NH3-CrMo6 hybrid crystal as an inorganic–organic hybrid laser.
Simplified PCR-Based Quantification of Proteins with DNA Aptamers and Methylcellulose as a Blocking Agent
Authors: Redcenko Oleksij , Tumova Magda , Draber Petr
Published: December 2023

Due to their unique three-dimensional structure, DNA or RNA oligonucleotide aptamers bind to various molecules with high affinity and specificity. Aptamers, alone or in combination with antibodies, can be used to sensitively quantify target molecules by quantitative real-time polymerase chain reaction (qPCR). However, the assays are often complicated and unreliable. In this study, we explored the feasibility of performing the entire assay on wells of routinely used polypropylene PCR plates. We found that polypropylene wells efficiently bind proteins. This allows the entire assay to be run in a single well. To minimize nonspecific binding of the assay components to the polypropylene wells, we tested various blocking agents and identified methylcellulose as an effective alternative to the commonly used BSA. Methylcellulose not only demonstrates comparable or superior blocking capabilities but also offers the advantage of a well-defined composition and non-animal origin. Our findings support the utilization of aptamers, either alone or in combination with antibodies, for sensitive quantification of selected molecules immobilized in polypropylene PCR wells in a streamlined one-well qPCR assay under well-defined conditions.
The Extended Cleavage Specificity of Channel Catfish Granzyme-like II, A Highly Specific Elastase, Expressed by Natural Killer-like Cells
Authors: Thorpe Michael , Akula Srinivas , Fu Zhirong , Hellman Lars
Published: December 2023

The extended cleavage specificity of catfish granzyme-like II has been characterized using substrate phage display. The preference for particular amino acids at and surrounding the cleavage site was further validated by using a panel of recombinant substrates. This serine protease, which has previously been isolated as cDNA from a catfish natural killer-like cell line showed a preference for Ala in the P1 position of the substrate, and for multiple basic amino acids N-terminally of the cleavage site. A closely related zebrafish serine protease (zebrafish esterase-like) showed a very similar cleavage specificity, indicating an evolutionary conservation of this protease specificity among various fish species. Two catfish serine proteases, originating from NK-like cells, have now been isolated and characterized. One of them is highly specific met-ase with similar characteristics as the mammalian granzyme M. This enzyme may be involved in the induction of apoptosis in virus-infected cells, with a potential target in (catfish) caspase 6. In contrast to catfish granzyme-like I, the second enzyme analyzed here does not seem to have a direct counterpart in mammalian NK cells, and its role in the immune function of catfish NK cells is, therefore, still not known. However, this enzyme seems to be able to cleave a number of cytoskeletal proteins, indicating a separate strategy to induce apoptosis in target cells. Both of these enzymes are very interesting targets for further studies of their roles in catfish immunity, as enzymes with similar specificities have also been identified in zebrafish.
Systematic Multiomic Analysis of PKHD1L1 Gene Expression and Its Role as a Predicting Biomarker for Immune Cell Infiltration in Skin Cutaneous Melanoma and Lung Adenocarcinoma
Authors: Kang Ji Young , Yang Jisun , Lee Haeryung , Park Soochul , Gil Minchan , Kim Kyung Eun
Published: December 2023

The identification of genetic factors that regulate the cancer immune microenvironment is important for understanding the mechanism of tumor progression and establishing an effective treatment strategy. Polycystic kidney and hepatic disease 1-like protein 1 (PKHD1L1) is a large transmembrane protein that is highly expressed in immune cells; however, its association with tumor progression remains unclear. Here, we systematically analyzed the clinical relevance of PKHD1L1 in the tumor microenvironment in multiple cancer types using various bioinformatic tools. We found that the PKHD1L1 mRNA expression levels were significantly lower in skin cutaneous melanoma (SKCM) and lung adenocarcinoma (LUAD) than in normal tissues. The decreased expression of PKHD1L1 was significantly associated with unfavorable overall survival (OS) in SKCM and LUAD. Additionally, PKHD1L1 expression was positively correlated with the levels of infiltrating B cells, cluster of differentiation (CD)-8+ T cells, and natural killer (NK) cells, suggesting that the infiltration of immune cells could be associated with a good prognosis due to increased PKHD1L1 expression. Gene ontology (GO) analysis also revealed the relationship between PKHD1L1-co-altered genes and the activation of lymphocytes, including B and T cells. Collectively, this study shows that PKHD1L1 expression is positively correlated with a good prognosis via the induction of immune infiltration, suggesting that PKHD1L1 has potential prognostic value in SKCM and LUAD.
Control Theory and Systems Biology: Potential Applications in Neurodegeneration and Search for Therapeutic Targets
Authors: Angarita-Rodríguez Andrea , González-Giraldo Yeimy , Rubio-Mesa Juan J. , Aristizábal Andrés Felipe , Pinzón Andrés , González Janneth
Published: December 2023

Control theory, a well-established discipline in engineering and mathematics, has found novel applications in systems biology. This interdisciplinary approach leverages the principles of feedback control and regulation to gain insights into the complex dynamics of cellular and molecular networks underlying chronic diseases, including neurodegeneration. By modeling and analyzing these intricate systems, control theory provides a framework to understand the pathophysiology and identify potential therapeutic targets. Therefore, this review examines the most widely used control methods in conjunction with genomic-scale metabolic models in the steady state of the multi-omics type. According to our research, this approach involves integrating experimental data, mathematical modeling, and computational analyses to simulate and control complex biological systems. In this review, we find that the most significant application of this methodology is associated with cancer, leaving a lack of knowledge in neurodegenerative models. However, this methodology, mainly associated with the Minimal Dominant Set (MDS), has provided a starting point for identifying therapeutic targets for drug development and personalized treatment strategies, paving the way for more effective therapies.
Exploring Optimal Biomarker Sources: A Comparative Analysis of Exosomes and Whole Plasma in Fasting and Non-Fasting Conditions for Liquid Biopsy Applications
Authors: Nasu Masaki , Khadka Vedbar S. , Jijiwa Mayumi , Kobayashi Ken , Deng Youping
Published: December 2023

The study of liquid biopsy with plasma samples is being conducted to identify biomarkers for clinical use. Exosomes, containing nucleic acids and metabolites, have emerged as possible sources for biomarkers. To evaluate the effectiveness of exosomes over plasma, we analyzed the small non-coding RNAs (sncRNAs) and metabolites extracted from exosomes in comparison to those directly extracted from whole plasma under both fasting and non-fasting conditions. We found that sncRNA profiles were not affected by fasting in either exosome or plasma samples. Our results showed that exosomal sncRNAs were found to have more consistent profiles. The plasma miRNA profiles contained high concentrations of cell-derived miRNAs that were likely due to hemolysis. We determined that certain metabolites in whole plasma exhibited noteworthy concentration shifts in relation to fasting status, while others did not. Here, we propose that (1) fasting is not required for a liquid biopsy study that involves both sncRNA and metabolomic profiling, as long as metabolites that are not influenced by fasting status are selected, and (2) the utilization of exosomal RNAs promotes robust and consistent findings in plasma samples, mitigating the impact of batch effects derived from hemolysis. These findings advance the optimization of liquid biopsy methodologies for clinical applications.
Beta Blockade Prevents Cardiac Morphological and Molecular Remodelling in Experimental Uremia
Authors: Chinnappa Shanmugakumar , Maqbool Azhar , Viswambharan Hema , Mooney Andrew , Denby Laura , Drinkhill Mark
Published: December 2023

Heart failure and chronic kidney disease (CKD) share several mediators of cardiac pathological remodelling. Akin to heart failure, this remodelling sets in motion a vicious cycle of progressive pathological hypertrophy and myocardial dysfunction in CKD. Several decades of heart failure research have shown that beta blockade is a powerful tool in preventing cardiac remodelling and breaking this vicious cycle. This phenomenon remains hitherto untested in CKD. Therefore, we set out to test the hypothesis that beta blockade prevents cardiac pathological remodelling in experimental uremia. Wistar rats had subtotal nephrectomy or sham surgery and were followed up for 10 weeks. The animals were randomly allocated to the beta blocker metoprolol (10 mg/kg/day) or vehicle. In vivo and in vitro cardiac assessments were performed. Cardiac tissue was extracted, and protein expression was quantified using immunoblotting. Histological analyses were performed to quantify myocardial fibrosis. Beta blockade attenuated cardiac pathological remodelling in nephrectomised animals. The echocardiographic left ventricular mass and the heart weight to tibial length ratio were significantly lower in nephrectomised animals treated with metoprolol. Furthermore, beta blockade attenuated myocardial fibrosis associated with subtotal nephrectomy. In addition, the Ca++- calmodulin-dependent kinase II (CAMKII) pathway was shown to be activated in uremia and attenuated by beta blockade, offering a potential mechanism of action. In conclusion, beta blockade attenuated hypertrophic signalling pathways and ameliorated cardiac pathological remodelling in experimental uremia. The study provides a strong scientific rationale for repurposing beta blockers, a tried and tested treatment in heart failure, for the benefit of patients with CKD.
Single-Molecule Imaging Reveals Differential AT1R Stoichiometry Change in Biased Signaling
Authors: Qin Gege , Xu Jiachao , Liang Yuxin , Fang Xiaohong
Published: December 2023

G protein-coupled receptors (GPCRs) represent promising therapeutic targets due to their involvement in numerous physiological processes mediated by downstream G protein- and β-arrestin-mediated signal transduction cascades. Although the precise control of GPCR signaling pathways is therapeutically valuable, the molecular details for governing biased GPCR signaling remain elusive. The Angiotensin II type 1 receptor (AT1R), a prototypical class A GPCR with profound implications for cardiovascular functions, has become a focal point for biased ligand-based clinical interventions. Herein, we used single-molecule live-cell imaging techniques to evaluate the changes in stoichiometry and dynamics of AT1R with distinct biased ligand stimulations in real time. It was revealed that AT1R existed predominantly in monomers and dimers and underwent oligomerization upon ligand stimulation. Notably, β-arrestin-biased ligands induced the formation of higher-order aggregates, resulting in a slower diffusion profile for AT1R compared to G protein-biased ligands. Furthermore, we demonstrated that the augmented aggregation of AT1R, triggered by activation from each biased ligand, was completely abrogated in β-arrestin knockout cells. These findings furnish novel insights into the intricate relationship between GPCR aggregation states and biased signaling, underscoring the pivotal role of molecular behaviors in guiding the development of selective therapeutic agents.
Comparative Analysis of Differential Cellular Transcriptome and Proteome Regulation by HIV-1 and HIV-2 Pseudovirions in the Early Phase of Infection
Authors: Linkner Tamás Richárd , Ambrus Viktor , Kunkli Balázs , Szojka Zsófia Ilona , Kalló Gergő , Csősz Éva , Kumar Ajneesh , Emri Miklós , Tőzsér József , Mahdi Mohamed
Published: December 2023

In spite of the similar structural and genomic organization of human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2), striking differences exist between them in terms of replication dynamics and clinical manifestation of infection. Although the pathomechanism of HIV-1 infection is well characterized, relatively few data are available regarding HIV-2 viral replication and its interaction with host–cell proteins during the early phase of infection. We utilized proteo-transcriptomic analyses to determine differential genome expression and proteomic changes induced by transduction with HIV-1/2 pseudovirions during 8, 12 and 26 h time-points in HEK-293T cells. We show that alteration in the cellular milieu was indeed different between the two pseudovirions. The significantly higher number of genes altered by HIV-2 in the first two time-points suggests a more diverse yet subtle effect on the host cell, preparing the infected cell for integration and latency. On the other hand, GO analysis showed that, while HIV-1 induced cellular oxidative stress and had a greater effect on cellular metabolism, HIV-2 mostly affected genes involved in cell adhesion, extracellular matrix organization or cellular differentiation. Proteomics analysis revealed that HIV-2 significantly downregulated the expression of proteins involved in mRNA processing and translation. Meanwhile, HIV-1 influenced the cellular level of translation initiation factors and chaperones. Our study provides insight into the understudied replication cycle of HIV-2 and enriches our knowledge about the use of HIV-based lentiviral vectors in general.
Elucidating Differences in Early-Stage Centrosome Amplification in Primary and Immortalized Mouse Cells
Authors: Tanaka Masakazu , Yamada Masaki , Mushiake Masatoshi , Tsuda Masataka , Miwa Masanao
Published: December 2023

The centrosome is involved in cytoplasmic microtubule organization during interphase and in mitotic spindle assembly during cell division. Centrosome amplification (abnormal proliferation of centrosome number) has been observed in several types of cancer and in precancerous conditions. Therefore, it is important to elucidate the mechanism of centrosome amplification in order to understand the early stage of carcinogenesis. Primary cells could be used to better understand the early stage of carcinogenesis rather than immortalized cells, which tend to have various genetic and epigenetic changes. Previously, we demonstrated that a poly(ADP-ribose) polymerase (PARP) inhibitor, 3-aminobenzamide (3AB), which is known to be nontoxic and nonmutagenic, could induce centrosome amplification and chromosomal aneuploidy in CHO-K1 cells. In this study, we compared primary mouse embryonic fibroblasts (MEF) and immortalized MEF using 3AB. Although centrosome amplification was induced with 3AB treatment in immortalized MEF, a more potent PARP inhibitor, AG14361, was required for primary MEF. However, after centrosome amplification, neither 3AB in immortalized MEF nor AG14361 in primary MEF caused chromosomal aneuploidy, suggesting that further genetic and/or epigenetic change(s) are required to exhibit aneuploidy. The DNA-damaging agents doxorubicin and γ-irradiation can cause cancer and centrosome amplification in experimental animals. Although doxorubicin and γ-irradiation induced centrosome amplification and led to decreased p27Kip protein levels in immortalized MEF and primary MEF, the phosphorylation ratio of nucleophosmin (Thr199) increased in immortalized MEF, whereas it decreased in primary MEF. These results suggest that there exists a yet unidentified pathway, different from the nucleophosmin phosphorylation pathway, which can cause centrosome amplification in primary MEF.
Astragalus Complanatus Ethanol Attenuates Septic Shock by Exerting Anti-Inflammatory Effects on Macrophages
Authors: Hwang Yo Sep , Lim Jeewon , Yoon Hyang Ran , Park Seong-Hoon , Kim Aeyung , Jang Jun-Pil , Cho Hee Jun , Lee Hee Gu
Published: December 2023

Sepsis is a systemic inflammatory syndrome that results in multiple-organ failure caused by a dysregulated host immune response to microbial infection. Astragali complanati semen extract (ACSE) exhibits pharmacological activities, including antioxidant, anticancer, antiaging, and anti-diabetes effects. It is widely used in traditional medicine to treat liver and kidney diseases; however, the protective effect of ACSE on sepsis and its mechanisms are unknown. In the present study, we investigated the anti-inflammatory effects and potential mechanisms of the action of ACSE on sepsis. We show that ACSE improved survival rates in mouse models of acute sepsis induced by CLP (cecal ligation and puncture) and LPS stimulation. ACSE administration decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in sepsis-induced mice. Furthermore, ACSE reduced the levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the serum of septic mice. ACSE treatment inhibited the expression of these proinflammatory genes in LPS-stimulated J774 macrophages. Moreover, ACSE inhibited the phosphorylation of the IκB kinase (IKK) and the nuclear translocation of p65 NF-κB by LPS stimulation in macrophages. These results reveal the mechanism underlying the protective effect of ACSE against sepsis by inhibiting NF-κB activation and suggest that ACSE could be a potential therapeutic candidate to treat acute inflammatory diseases.
Component Recognition and Coordinate Extraction in Two-Dimensional Paper Drawings Using SegFormer
Authors: Gu Shengkun , Wang Dejiang
Published: December 2023

Within the domain of architectural urban informatization, the automated precision recognition of two-dimensional paper schematics emerges as a pivotal technical challenge. Recognition methods traditionally employed frequently encounter limitations due to the fluctuating quality of architectural drawings and the bounds of current image processing methodologies, inhibiting the realization of high accuracy. The research delineates an innovative framework that synthesizes refined semantic segmentation algorithms with image processing techniques and precise coordinate identification methods, with the objective of enhancing the accuracy and operational efficiency in the identification of architectural elements. A meticulously curated data set, featuring 13 principal categories of building and structural components, facilitated the comprehensive training and assessment of two disparate deep learning models. The empirical findings reveal that these algorithms attained mean intersection over union (MIoU) values of 96.44% and 98.01% on the evaluation data set, marking a substantial enhancement in performance relative to traditional approaches. In conjunction, the framework’s integration of the Hough Transform with SQL Server technology has significantly reduced the coordinate detection error rates for linear and circular elements to below 0.1% and 0.15%, respectively. This investigation not only accomplishes the efficacious transition from analog two-dimensional paper drawings to their digital counterparts, but also assures the precise identification and localization of essential architectural components within the digital image coordinate framework. These developments are of considerable importance in furthering the digital transition within the construction industry and establish a robust foundation for the forthcoming extension of data collections and the refinement of algorithmic efficacy.
The Effect of Organic Spacer Cations with Different Chain Lengths on Quasi-Two-Dimensional Perovskite Properties
Authors: Zhang Lei , Xia Mingze , Zhang Yuan , Song Li , Guo Xiwei , Zhang Yong , Wang Yulei , Xia Yuanqin
Published: December 2023

In the past 20 years, perovskite-related research has attracted wide attention. The related research into two-dimensional/quasi-two-dimensional perovskite has propelled the research of perovskite materials to a new height. To improve the properties of quasi-2D perovskite, improve the stability of materials, and achieve specific functions, using different types, volumes, and lengths of organic spacers is an essential method. In this paper, quasi-2D perovskites with EDA (ethylene diammonium), PDA (1,3-propanediammonium), and BDA (1,4-butanediammonium) (m = 2–4) as organic spacers were prepared, and the effects of different organic spacers on the 2D perovskite were investigated. The results show that the length of the organic spacer significantly impacts the perovskite’s properties. A shorter organic spacer can effectively reduce the quantum confinement and dielectric confinement in perovskite. It should be noted that if the organic spacer is too short, the stability of the quasi-2D perovskite will be greatly reduced.