bluuebunny/crossref_metadata_2025 huggingface dataset:
Expressing the Spatial Concepts of Interior Spaces in Residential Buildings of Huizhou, China: Narrative Methods of Wood-Carving Imagery
Authors: Fang Xuebing , Li Lili , Gao Yi , Liu Niu , Cheng Liangsong
Published: May 2024

In the interiors of ancient Huizhou buildings in China, a profusion of wood carvings are employed for decoration, with traditional research interpreting their function from decorative and aesthetic perspectives. However, this research suggests that the role of Huizhou wood carvings in interior spaces surpasses mere decoration; they enhance the expression and experience of spatial concepts through narrative imagery. By analyzing the mechanism and intrinsic logic behind the spatial concepts formed in Huizhou residential buildings, this study investigates how wood-carving imagery contributes to shaping spatial concepts through narrative techniques, as well as their creativity and expressiveness in architectural design. Utilizing literature reviews, field surveys for case selection, and case analysis methods combined with observation, interviews, and measurements, this research ultimately employs image analysis to interpret the narrative structures and styles of wood-carving imagery in detail. This study reveals that (1) the spatial concepts of Huizhou residential buildings are influenced by traditional thought, social culture, and other factors, leading to an interweaving of material, cultural, and social spaces that results in a spatial concept characterized by harmony between heaven and humanity, clear hierarchy, and orderliness; (2) Huizhou wood-carvings, through their narrative images, actively engage in the production of spatial concepts, employing thematic juxtaposition narrative modes and utilizing singular-scene narration, composite-scene narration, and cyclical narration to articulate these concepts. These findings significantly deepen our comprehension of the relationship between the spatial concepts of Huizhou’s traditional residential architecture and social culture. By integrating cultural elements with spatial production theory, this research addresses the limitations of existing studies and augments their theoretical interpretative power. Additionally, clarifying the connection between the cultural elements of wood-carving imagery and the formation of spatial concepts offers a novel perspective on the study of Huizhou wood carvings, moving beyond their longstanding categorization as purely decorative elements.
Identification of Gene Expression in Different Stages of Breast Cancer with Machine Learning
Authors: Abidalkareem Ali , Ibrahim Ali K. , Abd Moaed , Rehman Oneeb , Zhuang Hanqi
Published: May 2024

Determining the tumor origin in humans is vital in clinical applications of molecular diagnostics. Metastatic cancer is usually a very aggressive disease with limited diagnostic procedures, despite the fact that many protocols have been evaluated for their effectiveness in prognostication. Research has shown that dysregulation in miRNAs (a class of non-coding, regulatory RNAs) is remarkably involved in oncogenic conditions. This research paper aims to develop a machine learning model that processes an array of miRNAs in 1097 metastatic tissue samples from patients who suffered from various stages of breast cancer. The suggested machine learning model is fed with miRNA quantitative read count data taken from The Cancer Genome Atlas Data Repository. Two main feature-selection techniques have been used, mainly Neighborhood Component Analysis and Minimum Redundancy Maximum Relevance, to identify the most discriminant and relevant miRNAs for their up-regulated and down-regulated states. These miRNAs are then validated as biological identifiers for each of the four cancer stages in breast tumors. Both machine learning algorithms yield performance scores that are significantly higher than the traditional fold-change approach, particularly in earlier stages of cancer, with Neighborhood Component Analysis and Minimum Redundancy Maximum Relevance achieving accuracy scores of up to 0.983 and 0.931, respectively, compared to 0.920 for the FC method. This study underscores the potential of advanced feature-selection methods in enhancing the accuracy of cancer stage identification, paving the way for improved diagnostic and therapeutic strategies in oncology.
Personalized Management of Malignant and Non-Malignant Ectopic Mediastinal Thyroid: A Proposed 10-Item Algorithm Approach
Authors: Carsote Mara , Ciobica Mihai-Lucian , Sima Oana-Claudia , Ciuche Adrian , Popa-Velea Ovidiu , Stanciu Mihaela , Popa Florina Ligia , Nistor Claudiu
Published: May 2024

We aimed to analyze the management of the ectopic mediastinal thyroid (EMT) with respect to EMT-related cancer and non-malignant findings related to the pathological report, clinical presentation, imaging traits, endocrine profile, connective tissue to the cervical (eutopic) thyroid gland, biopsy or fine needle aspiration (FNA) results, surgical techniques and post-operatory outcome. This was a comprehensive review based on revising any type of freely PubMed-accessible English, full-length original papers including the keywords “ectopic thyroid” and “mediastinum” from inception until March 2024. We included 89 original articles that specified EMTs data. We classified them into four main groups: (I) studies/case series (n = 10; N = 36 EMT patients); (II) malignant EMTs (N = 22 subjects; except for one newborn with immature teratoma in the EMT, only adults were reported; mean age of 62.94 years; ranges: 34 to 90 years; female to male ratio of 0.9). Histological analysis in adults showed the following: papillary (N = 11/21); follicular variant of the papillary type (N = 2/21); Hürthle cell thyroid follicular malignancy (N = 1/21); poorly differentiated (N = 1/21); anaplastic (N = 2/21); medullary (N = 1/21); lymphoma (N = 2/21); and MALT (mucosa-associated lymphoid tissue) (N = 1/21); (III) benign EMTs with no thyroid anomalies (N = 37 subjects; mean age of 56.32 years; ranges: 30 to 80 years; female to male ratio of 1.8); (IV) benign EMTs with thyroid anomalies (N = 23; female to male ratio of 5.6; average age of 52.1 years). This panel involved clinical/subclinical hypothyroidism (iatrogenic, congenital, thyroiditis-induced, and transitory type upon EMT removal); thyrotoxicosis (including autonomous activity in EMTs that suppressed eutopic gland); autoimmune thyroiditis/Graves’s disease; nodules/multinodular goiter and cancer in eutopic thyroid or prior thyroidectomy (before EMT detection). We propose a 10-item algorithm that might help navigate through the EMT domain. To conclude, across this focused-sample analysis (to our knowledge, the largest of its kind) of EMTs, the EMT clinical index of suspicion remains low; a higher rate of cancer is reported than prior data (18.8%), incident imagery-based detection was found in 10–14% of the EMTs; surgery offered an overall good outcome. A wide range of imagery, biopsy/FNA and surgical procedures is part of an otherwise complex personalized management.
Manufacturing of TiO2, Al2O3 and Y2O3 Ceramic Nanotubes for Application as Electrodes for Printable Electrochemical Sensors
Authors: Trandabat Alexandru Florentin , Ciobanu Romeo Cristian , Schreiner Oliver Daniel , Aradoaei Mihaela , Aradoaei Sebastian Teodor
Published: May 2024

This paper describes the process to obtain ceramic nanotubes from titanium dioxide, alumina and yttrium oxide by a feasible, replicable and reliable technology, including three stages, starting from an electrospinning process of poly(methyl methacrylate) solutions. A minimum diameter of 0.3 μm was considered optimal for PMMA nanofibers in order to maintain the structural stability of covered fibers, which, after ceramic film deposition, leads to a fiber diameter of 0.5–0.6 μm. After a chemical and physical analysis of the stages of obtaining ceramic nanotubes, in all cases, uniform deposition of a ceramic film on PMMA fibers and, finally, a uniform structure of ceramic nanotubes were noted. The technological purpose was to use such nanotubes as ingredients in screen-printing inks for electrochemical sensors, because no study directly targeted the subject of ceramic nanotube applications for printed electronics to date. The printing technology was analyzed in terms of the ink deposition process, printed electrode roughness vs. type of ceramic nanotubes, derived inks, thermal curing of the electrodes and the conductivity of electrodes on different support (rigid and flexible) at different curing temperatures. The experimental inks containing ceramic nanotubes can be considered feasible for printed electronics, because they offer fast curing at low temperatures, reasonable conductivity vs. electrode length, good printability on both ceramic or plastic (flexible) supports and good adhesion to surface after curing.
Blockchain and Smart Contracts for Digital Copyright Protection
Authors: Frattolillo Franco
Published: May 2024

In a global context characterized by a pressing need to find a solution to the problem of digital copyright protection, buyer-seller watermarking protocols based on asymmetric fingerprinting and adopting a “buyer-friendly” approach have proven effective in addressing such a problem. They can ensure high levels of usability and security. However, they usually resort to trusted third parties (TTPs) to guarantee the protection process, and this is often perceived as a relevant drawback since TTPs may cause conspiracy or collusion problems, besides the fact that they are generally considered as some sort of “big brother”. This paper presents a buyer-seller watermarking protocol that can achieve the right compromise between usability and security without employing a TTP. The protocol is built around previous experiences conducted in the field of protocols based on the buyer-friendly approach. Its peculiarity consists of exploiting smart contracts executed within a blockchain to implement preset and immutable rules that run automatically under specific conditions without control from some kind of central authority. The result is a simple, usable, and secure watermarking protocol able to do without TTPs.
Genetic Variants Underlying Plasticity in Natural Populations of Spadefoot Toads: Environmental Assessment versus Phenotypic Response
Authors: Isdaner Andrew J. , Levis Nicholas A. , Ehrenreich Ian M. , Pfennig David W.
Published: May 2024

Many organisms facultatively produce different phenotypes depending on their environment, yet relatively little is known about the genetic bases of such plasticity in natural populations. In this study, we describe the genetic variation underlying an extreme form of plasticity––resource polyphenism––in Mexican spadefoot toad tadpoles, Spea multiplicata. Depending on their environment, these tadpoles develop into one of two drastically different forms: a carnivore morph or an omnivore morph. We collected both morphs from two ponds that differed in which morph had an adaptive advantage and performed genome-wide association studies of phenotype (carnivore vs. omnivore) and adaptive plasticity (adaptive vs. maladaptive environmental assessment). We identified four quantitative trait loci associated with phenotype and nine with adaptive plasticity, two of which exhibited signatures of minor allele dominance and two of which (one phenotype locus and one adaptive plasticity locus) did not occur as minor allele homozygotes. Investigations into the genetics of plastic traits in natural populations promise to provide novel insights into how such complex, adaptive traits arise and evolve.
Cloning and Function Analysis of the CsTAU1 in Response to Salt–Alkali Stress
Authors: Zhang Fan , Li Dandan , Sa Rina , Wang Ling , Sheng Yunyan
Published: May 2024

To investigate the role of candidate genes for salt–alkali tolerance in cucumber (Cucumis sativus L.), this study screened CsTAU1 in the glutathione pathway from previous transcriptome data for cloning and functional analysis. Clone cucumber CsTAU1 contains one 675 bp open reading frame, containing one GST-N-Tau domain and one GST-C-Tau domain, and is expressed in cytoplasm. After successfully constructing overexpression vectors of CsTAU1 (+) and CsTAU1 (−), they were transferred into cucumber varieties ‘D1909’ (high salt alkali resistance) and ‘D1604’ (low salt alkali resistance) for salt–alkali resistance identification. It was found that under salt–alkali stress, CsTAU1 (+)-overexpressing plants showed strong resistance to salt–alkali stress, while CsTAU1 (−)-overexpressing plants showed the opposite situation. qRT-PCR analysis was performed on other glutathione pathway-related genes in CsTAU1-overexpressing plants. The expression patterns of LOC101219529 and LOC105434443 were the same as CsTAU1, and the introduction of CsTAU1 (+) increased the chlorophyll, α-Naphthylamine oxidation, glutathione S-transferase (GST), and catalase (CAT) content of cucumber. The research results provide a theoretical basis for cultivating salt–alkali-tolerant cucumber varieties.
Rare Genetic Developmental Disabilities: Mabry Syndrome (MIM 239300) Index Cases and Glycophosphatidylinositol (GPI) Disorders
Authors: Thompson Miles D. , Knaus Alexej
Published: May 2024

The case report by Mabry et al. (1970) of a family with four children with elevated tissue non-specific alkaline phosphatase, seizures and profound developmental disability, became the basis for phenotyping children with the features that became known as Mabry syndrome. Aside from improvements in the services available to patients and families, however, the diagnosis and treatment of this, and many other developmental disabilities, did not change significantly until the advent of massively parallel sequencing. As more patients with features of the Mabry syndrome were identified, exome and genome sequencing were used to identify the glycophosphatidylinositol (GPI) biosynthesis disorders (GPIBDs) as a group of congenital disorders of glycosylation (CDG). Biallelic variants of the phosphatidylinositol glycan (PIG) biosynthesis, type V (PIGV) gene identified in Mabry syndrome became evidence of the first in a phenotypic series that is numbered HPMRS1-6 in the order of discovery. HPMRS1 [MIM: 239300] is the phenotype resulting from inheritance of biallelic PIGV variants. Similarly, HPMRS2 (MIM 614749), HPMRS5 (MIM 616025) and HPMRS6 (MIM 616809) result from disruption of the PIGO, PIGW and PIGY genes expressed in the endoplasmic reticulum. By contrast, HPMRS3 (MIM 614207) and HPMRS4 (MIM 615716) result from disruption of post attachment to proteins PGAP2 (HPMRS3) and PGAP3 (HPMRS4). The GPI biosynthesis disorders (GPIBDs) are currently numbered GPIBD1-21. Working with Dr. Mabry, in 2020, we were able to use improved laboratory diagnostics to complete the molecular diagnosis of patients he had originally described in 1970. We identified biallelic variants of the PGAP2 gene in the first reported HPMRS patients. We discuss the longevity of the Mabry syndrome index patients in the context of the utility of pyridoxine treatment of seizures and evidence for putative glycolipid storage in patients with HPMRS3. From the perspective of the laboratory innovations made that enabled the identification of the HPMRS phenotype in Dr. Mabry’s patients, the need for treatment innovations that will benefit patients and families affected by developmental disabilities is clear.
Beautiful Birds and Hun Planes: Ford Madox Ford in the Early Age of Flight
Authors: Skinner Paul
Published: May 2024

Reactions to the Wright brothers’ achievement of the first sustained, controlled powered flight in December 1903 ranged from complete indifference to voluble celebration and evolved into convictions that ranged from a belief that war would be rendered impossible to confident predictions of invasion and widespread destruction. The policies and perceptions of institutions, governments and individuals were subject to constant revision and often abrupt reversal. When war came, the aeroplane, which began as an instrument of reconnaissance, rapidly became one more hazard among many for those at the front and a further point of division between combatants and civilians, for whom airships and air raids tended to loom larger. The first dynamic phase in the story of the aeroplane overlaps with the major early modernist period. This essay seeks to map, within that wider context, the experiences and responses of Ford Madox Ford. He began, like many others, with images of beauty and the natural world in that early stage when a functioning range of descriptive or comparative terms had yet to emerge. He encountered them next in the theatre of war during his service in France. His ambivalence towards aeroplanes was both similar to and different from his earlier responses to trains, cars and telephones. Their relative rarity, as well as their both physical and metaphorical distance, and Ford’s own apparent immunity to the glamour and dynamism of aviation enabled him to view them retrospectively and employ them in anecdote, autobiography and fiction as both threat and saviour.
Prevalence and Correlates of Health Risk Behaviors among University Students from a State in the Southern Region of Brazil
Authors: Guedes Dartagnan Pinto , de Lima Keila Aparecida , dos Santos Silva Andre Luis
Published: May 2024

Background: Surveys conducted in different regions of the world show that the prevalence rates of health risk behaviors (HRBs) in university students are sometimes higher than those found in non-university populations. This study aims to identify the prevalence rates and demographic and academic environment correlates associated with HRBs among Brazilian university students. Methods: In a cross-sectional epidemiological study, a random sample of 5310 university students answered an online questionnaire, with demographic (sex, age, skin color, marital status, and paid work) and academic setting information (housing type, size of campus, year, and shift of study), as well as items clustered in four HRB domains: personal safety and violence, sexual behavior and contraception, addictive substance use, eating habits, physical activity, and sleep. The data were analyzed statistically using bivariate analysis and hierarchical multiple regression. Results: The highest prevalence rates occurred in HRBs clustered in the domain of eating habits, physical activity, and sleep (>60%), while HRBs for personal security and violence were less prevalent (<15%). From 15% to 35% of university students assumed HRBs regarding addictive substance use, and approximately 50% reported risky sexual behavior. The university students most susceptible to HRBs were men, aged ≥ 22 years, living far from their family, studying on larger campuses, attending night classes, and with two or more years of study at the university. Conclusion: The findings suggest that policies and interventions in the university context aimed at students’ readiness to engage in a healthy lifestyle should target specific correlates associated with HRBs.
Trends in Health-Risk Behaviors and Psychological Distress among Australian First-Year University Students
Authors: Knapp Alison , Burrows Tracy , Whatnall Megan , Leigh Lucy , Leask Sarah , Hutchesson Melinda
Published: May 2024

University students are recognized as a high-risk population group who experience greater rates of poor health outcomes and mental ill-health. Commencing university is recognized as a major life transition, where students experience new financial, academic, environmental, and social pressures that can cause changes in their normal behaviors. This study explored trends in health-risk behaviors and psychological distress in commencing university students over four survey years. First-year undergraduate students, aged 17–24, from an Australian university were included. A secondary analysis was performed on data collected via cross-sectional surveys on four occasions (2016, 2017, 2019, 2020). Crude logistic regression models were utilized to investigate the association between meeting guidelines and survey year. Odds ratios for the pairwise comparison between each year are reported. In this analysis, 1300 (2016), 484 (2017), 456 (2019), and 571 (2020) students were included. Analyses showed two clear trends: students’ probability of being at high/very high risk of psychological distress (35–55%) and consuming breakfast daily (44–55%) consistently worsened over the four survey years. These findings suggest that the odds of psychological distress and daily breakfast consumption worsened over time, whilst the proportion of students engaging in some health-risk behaviors was high, highlighting the importance of early intervention during the transition to university.
The Prevalence of Caregiving among Young People
Authors: Lam Lawrence T. , Lam Mary K.
Published: May 2024

With the increasing number of people with chronic diseases and disabilities, the number of family members as caregivers have also been growing. Despite the attention paid to caregiving in recent years, little is known about caregiving among young people, particularly its global prevalence. The lack of information has important implications for health policy and management, resulting in the inability to form appropriate evidence-based policies and managerial decision making. This study aims to derive an estimate of the prevalence of caregiving among young people through a systematic review of the current literature. The results of this study revealed a prevalence of caregiving among younger adolescents of between 1.1% (1.06–1.14%) and 12.0% (11.02–12.98%). However, the assessment of caregiving varies across studies, and all were conducted in developed countries. These results provide information on the burden of caregiving in young people and reveal the lack of global information, calling for more research on and attention to this specific population.
Mindfulness in Pregnancy and Postpartum: Protocol of a Pilot Randomized Trial of Virtually Delivered Mindfulness-Based Cognitive Therapy to Promote Well-Being during the Perinatal Period
Authors: Donofry Shannon D. , Winograd Dayna , Kothari Diva , Call Christine C. , Magee Kelsey E. , Jouppi Riley J. , Conlon Rachel P. Kolko , Levine Michele D.
Published: May 2024

Background: During the period from pregnancy through the first year postpartum, vulnerable individuals are at elevated risk for the onset or worsening of psychological distress, and accessible (e.g., virtually delivered) mental health interventions are needed. Research suggests that Mindfulness-Based Cognitive Therapy (MBCT) can effectively mitigate psychological distress, although few studies have evaluated MBCT in the perinatal period, and samples have been clinically homogenous. Thus, we have designed and are conducting a pilot trial of virtually delivered MBCT with pregnant individuals experiencing a range of psychological symptoms to assess its feasibility and preliminarily explore its effectiveness. Here, we present the study protocol. Methods: Eligible participants (target N = 70) are ≥18 years with pregnancies between 12 and 30 weeks of gestation. Participants complete a diagnostic interview, self-report symptom ratings, and a computerized cognitive battery assessing self-regulation at the baseline. Participants are then randomized to either MBCT or care as usual. The MBCT intervention involves eight weekly group sessions delivered virtually, with each session focusing on a mindfulness practice followed by group discussion and skill development. Participants in the intervention group are also encouraged to practice mindfulness skills between sessions. Participants in the control condition are provided with information about mindfulness and treatment resources. Baseline measures are repeated following the eight-week intervention period and at three months postpartum. Conclusions: This pilot study is designed to evaluate the feasibility of virtually delivered MBCT and explore group differences in psychological symptoms during the perinatal period, and will lay the foundation for a larger clinical trial focused on optimizing this intervention to improve psychological functioning among diverse pregnant individuals.
Pre-Incisional and Multiple Intradermal Injection of N-Acetylcysteine Slightly Improves Incisional Wound Healing in an Animal Model
Authors: Pascal Wiktor , Smoliński Antoni , Gotowiec Mateusz , Wojtkiewicz Marta , Stachura Albert , Pełka Kacper , Kopka Michał , Quinn Kyle P. , Woessner Alan E. , Grzelecki Dariusz , Włodarski Paweł
Published: May 2024

The objective of this study was to investigate if delivering multiple doses of N-acetylcysteine (NAC) post-surgery in addition to pre-incisional administration significantly impacts the wound healing process in a rat model. Full-thickness skin incisions were carried out on the dorsum of 24 Sprague-Dawley rats in six locations. Fifteen minutes prior to the incision, half of the sites were treated with a control solution, with the wounds on the contralateral side treated with solutions containing 0.015%, 0.03% and 0.045% of NAC. In the case of the NAC treated group, further injections were given every 8 h for three days. On days 3, 7, 14 and 60 post-op, rats were sacrificed to gather material for the histological analysis, which included histomorphometry, collagen fiber organization analysis, immunohistochemistry and Abramov scale scoring. It was determined that scars treated with 0.015% NAC had significantly lower reepithelization than the control at day 60 post-op (p = 0.0018). Scars treated with 0.045% NAC had a significantly lower collagen fiber variance compared to 0.015% NAC at day 14 post-op (p = 0.02 and p = 0.04) and a lower mean scar width than the control at day 60 post-op (p = 0.0354 and p = 0.0224). No significant differences in the recruitment of immune cells and histological parameters were found. The results point to a limited efficacy of multiple NAC injections post-surgery in wound healing.
The YABBY Transcription Factor, SlYABBY2a, Positively Regulates Fruit Septum Development and Ripening in Tomatoes
Authors: Shen Hui , Luo Baobing , Ding Yingfeng , Xiao Haojun , Chen Guoping , Yang Zhengan , Hu Zongli , Wu Ting
Published: May 2024

The tomato fruit is a complex organ and is composed of various structures from the inside out, such as columella, septum, and placenta. However, our understanding of the development and function of these internal structures remains limited. In this study, we identified a plant-specific YABBY protein, SlYABBY2a, in the tomato (Solanum lycopersicum). SlYABBY2a exhibits relatively high expression levels among the nine YABBY genes in tomatoes and shows specific expression in the septum of the fruit. Through the use of a gene-editing technique performed by CRISPR/Cas9, we noticed defects in septum development in the Slyabby2a mutant fruits, leading to the inward concavity of the fruit pericarp and delayed septum ripening. Notably, the expression levels of key genes involved in auxin (SlFZY4, SlFZY5, and SlFZY6) and ethylene (SlACS2) biosynthesis were significantly downregulated in the septum of the Slalkbh10b mutants. Furthermore, the promoter activity of SlYABBY2a was regulated by the ripening regulator, SlTAGL1, in vivo. In summary, these discoveries provide insights into the positive regulation of SlYABBY2a on septum development and ripening and furnish evidence of the coordinated regulation of the auxin and ethylene signaling pathways in the ripening process, which expands our comprehension of septum development in the internal structure of the fruit.
Broader Perspective on Atherosclerosis—Selected Risk Factors, Biomarkers, and Therapeutic Approach
Authors: Fularski Piotr , Czarnik Witold , Dąbek Bartłomiej , Lisińska Wiktoria , Radzioch Ewa , Witkowska Alicja , Młynarska Ewelina , Rysz Jacek , Franczyk Beata
Published: May 2024

Atherosclerotic cardiovascular disease (ASCVD) stands as the leading cause of mortality worldwide. At its core lies a progressive process of atherosclerosis, influenced by multiple factors. Among them, lifestyle-related factors are highlighted, with inadequate diet being one of the foremost, alongside factors such as cigarette smoking, low physical activity, and sleep deprivation. Another substantial group of risk factors comprises comorbidities. Amongst others, conditions such as hypertension, diabetes mellitus (DM), chronic kidney disease (CKD), or familial hypercholesterolemia (FH) are included here. Extremely significant in the context of halting progression is counteracting the mentioned risk factors, including through treatment of the underlying disease. What is more, in recent years, there has been increasing attention paid to perceiving atherosclerosis as an inflammation-related disease. Consequently, efforts are directed towards exploring new anti-inflammatory medications to limit ASCVD progression. Simultaneously, research is underway to identify biomarkers capable of providing insights into the ongoing process of atherosclerotic plaque formation. The aim of this study is to provide a broader perspective on ASCVD, particularly focusing on its characteristics, traditional and novel treatment methods, and biomarkers that can facilitate its early detection.
Lemon Flavonoid Extract Eriomin Improves Pro/Antioxidant Status and Interferes with Cholesterol Metabolism without Affecting Serum Cholesterol Levels in Aged Rats
Authors: Šošić-Jurjević Branka , Borković-Mitić Slavica , Pavlović Slađan , Vlahović Dragana , Miler Marko , Cesar Thais , Ajdžanović Vladimir , Milenkovic Dragan , Stellaard Frans , Trifunović Svetlana , Filipović Branko , Lütjohann Dieter
Published: May 2024

This study aimed to assess the antioxidant capacity of lemon flavonoid extract Eriomin® (LE) and its impact on cholesterol metabolism in the context of healthy aging. We orally treated 24-month-old male Wistar rats with an LE (40 mg/kg) suspended in 0.3 mL of sunflower oil. At the same time, control groups received an equal volume of sunflower oil (CON) or remained untreated (ICON) daily for 4 weeks. We examined LE’s effects on superoxide dismutase and catalase- and glutathione-related enzyme activities, the concentration of lipid peroxides and protein carbonyls, total oxidant status (TOS) and antioxidant status (TAS), and oxidative stress index (OSI) in the liver, jejunum, and ileum. We also measured total cholesterol, its biosynthetic precursors (lanosterol, lathosterol, desmosterol), its degradation products (bile acid precursors) in the serum, liver, jejunum, and ileum, and serum phytosterols (intestinal absorption markers). LE reduced TOS, TAS, and OSI (p < 0.05) compared with control values, indicating its consistent antioxidant action in all examined organs. LE lowered hepatic desmosterol (p < 0.05) while also reducing 7α- and 24-hydroxycholesterol levels in the liver and ileum (p < 0.01). Serum cholesterol, hepatic gene expression, and the immunostaining intensity of CYP7A1 were unchanged. In conclusion, LE exerted non-enzymatic antioxidant effects and reduced cholesterol degradation, reducing its biosynthesis products, thereby maintaining serum cholesterol levels.
NF-κB Decoy Oligodeoxynucleotide-Loaded Poly Lactic-co-glycolic Acid Nanospheres Facilitate Socket Healing in Orthodontic Tooth Movement
Authors: Huang Albert chun-shuo , Ishida Yuji , Hatano-sato Kasumi , Oishi Shuji , Hosomichi Jun , Usumi-fujita Risa , Yamaguchi Hiroyuki , Tsujimoto Hiroyuki , Sasai Aiko , Ochi Ayaka , Ono Takashi
Published: May 2024

Orthodontic space closure following tooth extraction is often hindered by alveolar bone deficiency. This study investigates the therapeutic use of nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides loaded with polylactic-co-glycolic acid nanospheres (PLGA-NfDs) to mitigate alveolar bone loss during orthodontic tooth movement (OTM) following the bilateral extraction of maxillary first molars in a controlled experiment involving forty rats of OTM model with ethics approved. The decreased tendency of the OTM distance and inclination angle with increased bone volume and improved trabecular bone structure indicated minimized alveolar bone destruction. Reverse transcription-quantitative polymerase chain reaction and histomorphometric analysis demonstrated the suppression of inflammation and bone resorption by downregulating the expression of tartrate-resistant acid phosphatase, tumor necrosis factor-α, interleukin-1β, cathepsin K, NF-κB p65, and receptor activator of NF-κB ligand while provoking periodontal regeneration by upregulating the expression of alkaline phosphatase, transforming growth factor-β1, osteopontin, and fibroblast growth factor-2. Importantly, relative gene expression over the maxillary second molar compression side in proximity to the alveolus highlighted the pharmacological effect of intra-socket PLGA-NfD administration, as evidenced by elevated osteocalcin expression, indicative of enhanced osteocytogenesis. These findings emphasize that locally administered PLGA-NfD serves as an effective inflammatory suppressor and yields periodontal regenerative responses following tooth extraction.
The Changes of Amino-Acid Metabolism between Wheat and Rice during Early Growth under Flooding Stress
Authors: Komatsu Setsuko , Egishi Mayu , Ohno Toshihisa
Published: May 2024

Floods induce hypoxic stress and reduce wheat growth. On the other hand, rice is a semi-aquatic plant and usually grows even when partially submerged. To clarify the dynamic differences in the cellular mechanism between rice and wheat under flooding stress, morphological and biochemical analyses were performed. Although the growth of wheat in the early stage was significantly suppressed due to flooding stress, rice was hardly affected. Amino-acid analysis revealed significant changes in amino acids involved in the gamma-aminobutyric acid (GABA) shunt and anaerobic/aerobic metabolism. Flood stress significantly increased the contents of GABA and glutamate in wheat compared with rice, though the abundances of glutamate decarboxylase and succinyl semialdehyde dehydrogenase did not change. The abundance of alcohol dehydrogenase and pyruvate carboxylase increased in wheat and rice, respectively. The contents of aspartic acid and pyruvic acid increased in rice root but remained unchanged in wheat; however, the abundance of aspartate aminotransferase increased in wheat root. These results suggest that flooding stress significantly inhibits wheat growth through upregulating amino-acid metabolism and increasing the alcohol-fermentation system compared to rice. When plant growth is inhibited by flooding stress and the aerobic-metabolic system is activated, GABA content increases.
Integrated Membrane Process in Organic Media: Combining Organic Solvent Ultrafiltration, Nanofiltration, and Reverse Osmosis to Purify and Concentrate the Phenolic Compounds from Wet Olive Pomace
Authors: Sánchez-Arévalo Carmen M. , Aldegheri Fausto , Vincent-Vela M. Cinta , Álvarez-Blanco Silvia
Published: May 2024

Phenolic compounds from a hydroalcoholic extract of wet olive pomace were purified and concentrated by an integrated membrane process in organic media. First, UF010104 (Solsep BV) and UP005 (Microdyn Nadir) membranes were tested to be implemented in the ultrafiltration stage, with the aim of purifying the extract and obtaining a permeate enriched in phenolic compounds. Despite the high flux observed with the UF010104 membrane (20.4 ± 0.7 L·h−1·m−2, at 2 bar), the UP005 membrane was selected because of a more suitable selectivity. Even though some secoiridoids were rejected, the permeate stream obtained with this membrane contained high concentrations of valuable simple phenols and phenolic acids, whereas sugars and macromolecules were retained. Then, the ultrafiltration permeate was subjected to a nanofiltration step employing an NF270 membrane (DuPont) for a further purification and fractionation of the phenolic compounds. The permeate flux was 50.2 ± 0.2 L·h−1·m−2, working at 15 bar. Hydroxytyrosol and some phenolic acids (such as vanillic acid, caffeic acid, and ferulic acid) were recovered in the permeate, which was later concentrated by reverse osmosis employing an NF90 membrane. The permeate flux obtained with this membrane was 15.3 ± 0.3 L·h−1·m−2. The concentrated phenolic mixture that was obtained may have important applications as a powerful antioxidant and for the prevention of diabetes and neurodegenerative diseases.
Sox10 Activity and the Timing of Schwann Cell Differentiation Are Controlled by a Tle4-Dependent Negative Feedback Loop
Authors: Aberle Tim , Walter Anna , Piefke Sandra , Hillgärtner Simone , Wüst Hannah M. , Wegner Michael , Küspert Melanie
Published: May 2024

The HMG-domain containing transcription factor Sox10 plays a crucial role in regulating Schwann cell survival and differentiation and is expressed throughout the entire Schwann cell lineage. While its importance in peripheral myelination is well established, little is known about its role in the early stages of Schwann cell development. In a search for direct target genes of Sox10 in Schwann cell precursors, the transcriptional co-repressor Tle4 was identified. At least two regions upstream of the Tle4 gene appear involved in mediating the Sox10-dependent activation. Once induced, Tle4 works in tandem with the bHLH transcriptional repressor Hes1 and exerts a dual inhibitory effect on Sox10 by preventing the Sox10 protein from transcriptionally activating maturation genes and by suppressing Sox10 expression through known enhancers of the gene. This mechanism establishes a regulatory barrier that prevents premature activation of factors involved in differentiation and myelin formation by Sox10 in immature Schwann cells. The identification of Tle4 as a critical downstream target of Sox10 sheds light on the gene regulatory network in the early phases of Schwann cell development. It unravels an elaborate regulatory circuitry that fine-tunes the timing and extent of Schwann cell differentiation and myelin gene expression.
Regulation of T Lymphocyte Functions through Calcium Signaling Modulation by Nootkatone
Authors: Lee Ji , Kim Jintae , Park Su , Nam Joo , Kim Hyun , Kim Woo
Published: May 2024

Recent advancements in understanding the intricate molecular mechanisms underlying immunological responses have underscored the critical involvement of ion channels in regulating calcium influx, particularly in inflammation. Nootkatone, a natural sesquiterpenoid found in Alpinia oxyphylla and various citrus species, has gained attention for its diverse pharmacological properties, including anti-inflammatory effects. This study aimed to elucidate the potential of nootkatone in modulating ion channels associated with calcium signaling, particularly CRAC, KV1.3, and KCa3.1 channels, which play pivotal roles in immune cell activation and proliferation. Using electrophysiological techniques, we demonstrated the inhibitory effects of nootkatone on CRAC, KV1.3, and KCa3.1 channels in HEK293T cells overexpressing respective channel proteins. Nootkatone exhibited dose-dependent inhibition of channel currents, with IC50 values determined for each channel. Nootkatone treatment did not significantly affect cell viability, indicating its potential safety for therapeutic applications. Furthermore, we observed that nootkatone treatment attenuated calcium influx through activated CRAC channels and showed anti-proliferative effects, suggesting its role in regulating inflammatory T cell activation. These findings highlight the potential of nootkatone as a natural compound for modulating calcium signaling pathways by targeting related key ion channels and it holds promise as a novel therapeutic agent for inflammatory disorders.
Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments
Authors: Kim Jun Yong , Lee Seung Yeon , Cha Seung-Gyu , Park Jung Min , Song Duck Hyun , Lee Sang-Hyuk , Hwang Dong-Youn , Kim Byoung Ju , Rho Seungsoo , Park Chun Gwon , Rhim Won-Kyu , Han Dong Keun
Published: May 2024

Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases.
Cartilage Oligomeric Matrix Protein in Osteoarthritis and Obesity—Do New Considerations Emerge?
Authors: Lambova Sevdalina Nikolova , Batsalova Tsvetelina , Moten Dzhemal , Dzhambazov Balik
Published: May 2024

The diagnosis of osteoarthritis (OA) is based on radiological changes that are delayed, along with clinical symptoms. Early and very early diagnosis at the stage of molecular pathology may eventually offer an opportunity for early therapeutic intervention that may retard and prevent future damage. Cartilage oligomeric matrix protein (COMP) is a non-collagenous extracellular matrix protein that promotes the secretion and aggregation of collagen and contributes to the stability of the extracellular matrix. There are contradictory literature data and currently, the parameter is used only for scientific purposes and its significance is not well-determined. The serum level of COMP in patients with metabolic type OA of the knee has not been evaluated. The aim of the study was to analyze serum COMP levels in metabolic knee OA and controls with different BMI. Our results showed that the mean COMP values were significantly higher in the control group (1518.69 ± 232.76 ng/mL) compared to the knee OA patients (1294.58 ± 360.77 ng/mL) (p = 0.0012). This may be related to the smaller cartilage volume in OA patients. Additionally, COMP levels negatively correlated with disease duration (p = 0.04). The COMP level in knee OA with BMI below 30 kg/m2 (n = 61, 1304.50 ± 350.60 ng/mL) was higher compared to cases with BMI ≥ 30 kg/m2 (n = 76, 1286.63 ± 370.86 ng/mL), but the difference was not significant (p = 0.68). Whether this finding is related to specific features in the evolution of the metabolic type of knee OA remains to be determined. Interestingly, comparison of COMP levels in the controls with different BMI revealed significantly higher values in overweight and obese individuals (1618.36 ± 203.76 ng/mL in controls with BMI ≥ 25 kg/m2, n = 18, 1406.61 ± 216.41 ng/mL, n = 16; p = 0.0092). Whether this finding is associated with increased expression of COMP in the adipose tissue or with more intensive cartilage metabolism in relation to higher biomechanical overload in obese patients, considering the earlier development of metabolic type knee OA as an isolated finding, remains to be determined.
Evaluation of New Approaches to Depression Treatment Using an Animal Model of Pharmacoresistant Depression
Authors: Zvozilova Alexandra , Bukatova Stanislava , Koprdova Romana , Mach Mojmir
Published: May 2024

Depression is emerging as the predominant psychiatric disorder globally. Despite the wide availability of antidepressants, up to 30% of patients exhibit poor response to treatment, falling into the category of treatment-resistant depression (TRD). This underscores the need for the exploration of novel therapeutic options. Our work aims to study the effect of chronic administration of the pyridoindole derivative SMe1EC2M3, a triple reuptake inhibitor, and the combination of zoletil and venlafaxine under conditions of stress induced by a 4-week chronic mild stress (CMS) procedure in Wistar-Kyoto male rats as an animal model of TRD. Therefore, we investigated the possible effect of the selected compounds in four experimental groups, i.e., stress + vehicle, stress + venlafaxine, stress + zoletil + venlafaxine and stress + SMe1EC2M3. The following variables were assessed: anhedonia in sucrose preference test (SPT), spontaneous locomotion and exploration in open field test (OF), anxiety-like behavior in elevated plus maze test (EPM), motivation and depressive-like behavior in forced swim test (FST) and nociception in tail flick test. We also evaluated cognition, particularly recognition memory, in the novel object recognition test (NOR). Sucrose preference was significantly increased in the SMe1EC2M3 group (p < 0.05) in comparison with the venlafaxine animals. In the OF, we observed a significantly higher number of entries into both the central and peripheral zones in the venlafaxine (p < 0.05 central zone; p ≤ 0.05 periphery zone) and SMe1EC2M3 (p < 0.05 central zone; p < 0.05 periphery zone) groups compared to the venlafaxine + zoletil group. SMe1EC2M3 was able to significantly increase the time of climbing in FST (p < 0.05) in comparison with the venlafaxine and control groups. The NOR test revealed a significantly higher discrimination ratio in the SMe1EC2M3 group (p < 0.05) compared to the control and venlafaxine groups. Analyses of the tail flick test showed a significant increase in reaction time to painful stimuli in the SMe1EC2M3 group (p < 0.05) in comparison to both the control and venlafaxine groups. Our findings suggest that SMe1EC2M3 has the potential to ameliorate some behavioral changes associated with TRD, and the venlafaxine + zoletil combination treatment was not a promising treatment alternative in the animal model of TRD.
DDCM: A Computational Strategy for Drug Repositioning Based on Support-Vector Regression Algorithm
Authors: Xu Manyi , Li Wan , He Jiaheng , Wang Yahui , Lv Junjie , He Weiming , Chen Lina , Zhi Hui
Published: May 2024

Computational drug-repositioning technology is an effective tool for speeding up drug development. As biological data resources continue to grow, it becomes more important to find effective methods to identify potential therapeutic drugs for diseases. The effective use of valuable data has become a more rational and efficient approach to drug repositioning. The disease–drug correlation method (DDCM) proposed in this study is a novel approach that integrates data from multiple sources and different levels to predict potential treatments for diseases, utilizing support-vector regression (SVR). The DDCM approach resulted in potential therapeutic drugs for neoplasms and cardiovascular diseases by constructing a correlation hybrid matrix containing the respective similarities of drugs and diseases, implementing the SVR algorithm to predict the correlation scores, and undergoing a randomized perturbation and stepwise screening pipeline. Some potential therapeutic drugs were predicted by this approach. The potential therapeutic ability of these drugs has been well-validated in terms of the literature, function, drug target, and survival-essential genes. The method’s feasibility was confirmed by comparing the predicted results with the classical method and conducting a co-drug analysis of the sub-branch. Our method challenges the conventional approach to studying disease–drug correlations and presents a fresh perspective for understanding the pathogenesis of diseases.