bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Key Soil Mineral Elements Affecting Sugars and Organic Acids of Jujube Fruit
Authors: Tong Panpan , Liao Guanglian , Liang Fengzhi , Lu Dengyang , Wu Cuiyun , Wang Jiangbo
Published: June 2024

Soil mineral elements are the key factors affecting fruit quality, but which soil elements affect the sugars and organic acids of jujube fruit is still not clear. In this study, the fruit and soil of 18 major producing areas of the Tarim Basin were studied. By measuring the sugar and acid content in the fruits and element contents in the soil, the main soil mineral elements affecting the sugar and acid content in jujube fruits were identified. The results showed that the sugar components were mainly sucrose, glucose and fructose, and the organic acid components were mainly succinic acid, citric acid and malic acid. The fruits near the Kunlun Mountains had a higher ratio of sugar-to-acid and sweet-to-acid. Some elements in the soil of the Tarim Basin are abundant, such as the elements Ca, Fe, Mn and B, but the contents of the elements NO3-N, NH4-N, Zn and Mo are low. The contents of Ca, Mg and Mn were positively correlated with the contents of glucose, fructose and galactose. And the Fe, Ca, Mg and Mn were the main factors affecting the sugars and organic acid contents. Our study provides theoretical support for rational fertilization and efficient cultivation management of jujube.
Enhancing Tomato Productivity and Quality in Moderately Saline Soils through Salicornia-Assisted Cultivation Methods: A Comparative Study
Authors: Santin Marco , Parichanon Prangthip , Sciampagna Maria Calogera , Ranieri Annamaria , Castagna Antonella
Published: June 2024

The presence of high salt in soils is a substantial abiotic constraint for agricultural activities worldwide, particularly in Mediterranean regions. Researchers have discovered a simple and efficient way to repair soils that have suffered from excessive salt use. They use plants that can overcome salt, like halophytes, to improve the soil quality. This research aimed to evaluate the tomato productivity and quality cultivated using different methods. We look at three different ways to grow tomatoes with the halophyte Salicornia europaea L. in a moderately salty soil: monoculture (only tomatoes), intercropping (mixed cultivation), and sequential cropping (growing tomatoes where halophytes were grown before). We considered how the different ways of managing crops affected tomato yield, biochemical factors in tomato plants (like phenolic and flavonoid contents), antioxidant levels, carotene profiles, and fruit quality and production. Sequential cropping showed the highest tomato productivity, while intercropping exhibited high concentrations of total phenolics, total flavonoids, carotenoids, and antioxidant capacity. The tomatoes had a sweet taste due to the higher total soluble solid content (TSSC) and maintained their quality due to the higher titratable acidity (TA).
Modeling the Impacts of Sea Level Rise Scenarios on the Amazon River Estuary
Authors: Crizanto Jonathan Luz P. , de Abreu Carlos Henrique M. , de Souza Everaldo B. , da Cunha Alan C.
Published: June 2024

The rise in the global mean sea level (MSL) is a significant consequence of climate change, attributed to both natural and anthropogenic forces. This phenomenon directly affects the dynamic equilibrium of Earth’s oceanic and estuarine ecosystems, particularly impacting the Amazon estuary. In this study, a numerical model was employed to investigate the long-term impacts of MSL fluctuations on key hydrodynamic parameters crucial to regional environmental dynamics. Our investigation was based on scenarios derived from Representative Concentration Pathways (RCPs) and Coupled Model Intercomparison Project Phase 5 (CMIP5) projections, incorporating MSL variations ranging from 30 to 150 cm above the current mean level. Following careful calibration and validation procedures, which utilized observational and in situ data, notably from field expeditions conducted in 2019, our simulations unveiled significant impacts on certain hydrodynamic parameters. Specifically, we observed a pronounced increase in diurnal tidal amplitude (p < 0.05) within the upstream sections of the North and South channels. Additionally, discernible alterations in water renewal rates throughout the estuary were noted, persisting for approximately 2 days during the dry season (p < 0.05). These findings provide valuable insights into the vulnerability of key parameters to hydrologic instability within the Amazonian coastal region. In conclusion, this study represents a pivotal scientific endeavor aimed at enhancing the preservation of aquatic ecosystems and advancing the environmental knowledge of the Lower Amazon River, with the goal of proactively informing measures to safeguard the current and future sustainability of these vital ecosystems.
‘How Your Spirit Is Travelling’—Understanding First Nations Peoples’ Experiences of Living Well with and after Cancer
Authors: de Groot Anneliese , Brown Bena , Lindsay Daniel , Gall Alana , Hewlett Nicole , Hickman Amy , Garvey Gail
Published: June 2024

As the number of people living with cancer increases, it is important to understand how people can live well with and after cancer. First Nations people diagnosed with cancer in Australia experience survival disparities relating to health service accessibility and a lack of understanding of cultural needs and lived experiences. This study aimed to amplify the voices of First Nations individuals impacted by cancer and advance the development of a culturally informed care pathway. Indigenist research methodology guided the relational and transformative approach of this study. Participants included varied cancer experts, including First Nations people living well with and after cancer, health professionals, researchers, and policy makers. Data were collected through online Yarning circles and analysed according to an inductive thematic approach. The experience of First Nations people living well with and after cancer is inextricably connected with family. The overall themes encompass hope, family, and culture and the four priority areas included the following: strength-based understanding of cancer, cancer information, access to healthcare and support, and holistic cancer services. Respect for culture is interwoven throughout. Models of survivorship care need to integrate family-centred cancer care to holistically support First Nations people throughout and beyond their cancer journey.
Microcystis viridis NIES-102 Cyanobacteria Lectin (MVL) Interacts with SARS-CoV-2 Spike Protein Receptor Binding Domains (RBDs) via Protein–Protein Interaction
Authors: Wang Zhengguang , Yang Zhihan , Shishido Mami , Daoudi Khadija , Hidaka Masafumi , Tateno Hiroaki , Futai Eugene , Ogawa Tomohisa
Published: June 2024

The emergence of coronavirus disease 2019 (COVID-19) posed a major challenge to healthcare systems worldwide, especially as mutations in the culprit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) complicated the development of vaccines and antiviral drugs. Therefore, the search for natural products with broad anti-SARS-CoV-2 capabilities is an important option for the prevention and treatment of similar infectious diseases. Lectins, which are widely recognized as antiviral agents, could contribute to the development of anti-SARS-CoV-2 drugs. This study evaluated the binding affinity of six lectins (including the cyanobacterial lectin from Microcystis viridis NIES-102 (MVL), and Jacalin, a lectin from the breadfruit, Artocarpus altilis) to the receptor binding domain (RBD) of the spike protein on the original (wild) SARS-CoV-2 and three of its mutants: Alpha, Delta, and Omicron. MVL and Jacalin showed distinct binding affinity to the RBDs of the four SARS-CoV-2 strains. The remaining four lectins (DB1, ConA, PHA-M and CSL3) showed no such binding affinity. Although the glycan specificities of MVL and Jacalin were different, they showed the same affinity for the spike protein RBDs of the four SARS-CoV-2 strains, in the order of effectiveness Alpha > Delta > original > Omicron. The verification of glycan-specific inhibition revealed that both lectins bind to RBDs by glycan-specific recognition, but, in addition, MVL binds to RBDs through protein–protein interactions.
Integrated Analysis of Microbiome and Metabolome Reveals Disease-Specific Profiles in Inflammatory Bowel Diseases and Intestinal Behçet’s Disease
Authors: Park Yehyun , Ahn Jae Bum , Kim Da Hye , Park I Seul , Son Mijeong , Kim Ji Hyung , Ma Hyun Woo , Kim Seung Won , Cheon Jae Hee
Published: June 2024

The gut microbial and metabolic characteristics of intestinal Behçet’s disease (BD), a condition sharing many clinical similarities with ulcerative colitis (UC) and Crohn’s disease (CD), are largely unexplored. This study investigated the gut microbial and metabolic characteristics of intestinal BD as well as potential biomarkers, comparing them with those in UC, CD, and healthy controls. Colon tissue and stool samples from 100 patients (35 UC, 30 CD, and 35 intestinal BD) and 41 healthy volunteers were analyzed using 16S ribosomal RNA sequencing to assess microbial diversity, taxonomic composition, and functional profiling. Plasma metabolomic analyses were performed using gas chromatography and ultra-performance liquid chromatography-mass spectrometry. Results indicated reduced microbial diversity in CD but not in intestinal BD, with intestinal BD showing fewer changes compared to controls yet distinct taxonomic features from UC, CD, and controls. Common alterations across all diseases included a reduction in beneficial bacteria producing short-chain fatty acids. Intestinal BD-specific changes featured a decreased abundance of Bacteroides fragilis. Metabolomic profiles in intestinal BD were similar to those in CD but distinct from those in UC, displaying significant changes in energy metabolism and genetic information processing. This integrative analysis revealed both shared and unique profiles in intestinal BD compared with UC, CD, and controls, advancing our understanding of the distinctive features of these diseases.
A Practical Guide to All-Atom and Coarse-Grained Molecular Dynamics Simulations Using Amber and Gromacs: A Case Study of Disulfide-Bond Impact on the Intrinsically Disordered Amyloid Beta
Authors: Smardz Pamela , Anila Midhun Mohan , Rogowski Paweł , Li Mai Suan , Różycki Bartosz , Krupa Pawel
Published: June 2024

Intrinsically disordered proteins (IDPs) pose challenges to conventional experimental techniques due to their large-scale conformational fluctuations and transient structural elements. This work presents computational methods for studying IDPs at various resolutions using the Amber and Gromacs packages with both all-atom (Amber ff19SB with the OPC water model) and coarse-grained (Martini 3 and SIRAH) approaches. The effectiveness of these methodologies is demonstrated by examining the monomeric form of amyloid-β (Aβ42), an IDP, with and without disulfide bonds at different resolutions. Our results clearly show that the addition of a disulfide bond decreases the β-content of Aβ42; however, it increases the tendency of the monomeric Aβ42 to form fibril-like conformations, explaining the various aggregation rates observed in experiments. Moreover, analysis of the monomeric Aβ42 compactness, secondary structure content, and comparison between calculated and experimental chemical shifts demonstrates that all three methods provide a reasonable choice to study IDPs; however, coarse-grained approaches may lack some atomistic details, such as secondary structure recognition, due to the simplifications used. In general, this study not only explains the role of disulfide bonds in Aβ42 but also provides a step-by-step protocol for setting up, conducting, and analyzing molecular dynamics (MD) simulations, which is adaptable for studying other biomacromolecules, including folded and disordered proteins and peptides.
Changes in Telomere Length in Leukocytes and Leukemic Cells after Ultrashort Electron Beam Radiation
Authors: Harutyunyan Tigran , Sargsyan Anzhela , Kalashyan Lily , Igityan Hovhannes , Grigoryan Bagrat , Davtyan Hakob , Aroutiounian Rouben , Liehr Thomas , Hovhannisyan Galina
Published: June 2024

Application of laser-generated electron beams in radiotherapy is a recent development. Accordingly, mechanisms of biological response to radiation damage need to be investigated. In this study, telomere length (TL) as endpoint of genetic damage was analyzed in human blood cells (leukocytes) and K562 leukemic cells irradiated with laser-generated ultrashort electron beam. Metaphases and interphases were analyzed in quantitative fluorescence in situ hybridization (Q-FISH) to assess TL. TLs were shortened compared to non-irradiated controls in both settings (metaphase and interphase) after irradiation with 0.5, 1.5, and 3.0 Gy in blood leukocytes. Radiation also caused a significant TL shortening detectable in the interphase of K562 cells. Overall, a negative correlation between TL and radiation doses was observed in normal and leukemic cells in a dose-dependent manner. K562 cells were more sensitive than normal blood cells to increasing doses of ultrashort electron beam radiation. As telomere shortening leads to genome instability and cell death, the results obtained confirm the suitability of this biomarker for assessing genotoxic effects of accelerated electrons for their further use in radiation therapy. Observed differences in TL shortening between normal and K562 cells provide an opportunity for further development of optimal radiation parameters to reduce side effects in normal cells during radiotherapy.
Peptides Used for Heavy Metal Remediation: A Promising Approach
Authors: Luo Yingyong , Zhang Yunfeng , Xiong Zhuang , Chen Xiaodie , Sha Ajia , Xiao Wenqi , Peng Lianxin , Zou Liang , Han Jialiang , Li Qiang
Published: June 2024

In recent years, heavy metal pollution has become increasingly prominent, severely damaging ecosystems and biodiversity, and posing a serious threat to human health. However, the results of current methods for heavy metal restoration are not satisfactory, so it is urgent to find a new and effective method. Peptides are the units that make up proteins, with small molecular weights and strong biological activities. They can effectively repair proteins by forming complexes, reducing heavy metal ions, activating the plant’s antioxidant defense system, and promoting the growth and metabolism of microorganisms. Peptides show great potential for the remediation of heavy metal contamination due to their special structure and properties. This paper reviews the research progress in recent years on the use of peptides to remediate heavy metal pollution, describes the mechanisms and applications of remediation, and provides references for the remediation of heavy metal pollution.
Axonal and Glial PIEZO1 and PIEZO2 Immunoreactivity in Human Clitoral Krause’s Corpuscles
Authors: Cuendias Patricia , Vega José A. , García-Suárez Olivia , Suazo Iván , Cobo Ramón , García-Piqueras Jorge , García-Mesa Yolanda
Published: June 2024

Krause’s corpuscles are typical of cutaneous mucous epithelia, like the lip vermillion or the glans clitoridis, and are associated with rapidly adapting low-threshold mechanoreceptors involved in gentle touch or vibration. PIEZO1 and PIEZO2 are transmembrane mechano-gated proteins that form a part of the cationic ion channels required for mechanosensitivity in mammalian cells. They are involved in somatosensitivity, especially in the different qualities of touch, but also in pain and proprioception. In the present study, immunohistochemistry and immunofluorescence were used to analyze the occurrence and cellular location of PIEZO1 and PIEZO2 in human clitoral Krause’s corpuscles. Both PIEZO1 and PIEZO2 were detected in Krause’s corpuscles in both the axon and the terminal glial cells. The presence of PIEZOs in the terminal glial cells of Kraus’s corpuscles is reported here for the first time. Based on the distribution of PIEZO1 and PIEZO2, it may be assumed they could be involved in mechanical stimuli, sexual behavior, and sexual pleasure.
Combined Ionizing Radiation Exposure by Gamma Rays and Carbon-12 Nuclei Increases Neurotrophic Factor Content and Prevents Age-Associated Decreases in the Volume of the Sensorimotor Cortex in Rats
Authors: Kokhan Viktor S. , Pikalov Vladimir A. , Chaprov Kirill , Gulyaev Mikhail V.
Published: June 2024

In orbital and ground-based experiments, it has been demonstrated that ionizing radiation (IR) can stimulate the locomotor and exploratory activity of rodents, but the underlying mechanism of this phenomenon remains undisclosed. Here, we studied the effect of combined IR (0.4 Gy γ-rays and 0.14 Gy carbon-12 nuclei) on the locomotor and exploratory activity of rats, and assessed the sensorimotor cortex volume by magnetic resonance imaging-based morphometry at 1 week and 7 months post-irradiation. The sensorimotor cortex tissues were processed to determine whether the behavioral and morphologic effects were associated with changes in neurotrophin content. The irradiated rats were characterized by increased locomotor and exploratory activity, as well as novelty-seeking behavior, at 3 days post-irradiation. At the same time, only unirradiated rats experienced a significant decrease in the sensorimotor cortex volume at 7 months. While there were no significant differences at 1 week, at 7 months, the irradiated rats were characterized by higher neurotrophin-3 and neurotrophin-4 content in the sensorimotor cortex. Thus, IR prevents the age-associated decrease in the sensorimotor cortex volume, which is associated with neurotrophic and neurogenic changes. Meanwhile, IR-induced increases in locomotor activity may be the cause of the observed changes.
Effects of the Interaction between Rumen Microbiota Density–VFAs–Hepatic Gluconeogenesis on the Adaptability of Tibetan Sheep to Plateau
Authors: Yang Wenxin , Sha Yuzhu , Chen Xiaowei , Liu Xiu , Wang Fanxiong , Wang Jiqing , Shao Pengyang , Chen Qianling , Gao Min , Huang Wei
Published: June 2024

During the adaptive evolution of animals, the host and its gut microbiota co-adapt to different elevations. Currently, there are few reports on the rumen microbiota–hepato-intestinal axis of Tibetan sheep at different altitudes. Therefore, the purpose of this study was to explore the regulatory effect of rumen microorganism–volatile fatty acids (VFAs)–VFAs transporter gene interactions on the key enzymes and genes related to gluconeogenesis in Tibetan sheep. The rumen fermentation parameters, rumen microbial densities, liver gluconeogenesis activity and related genes were determined and analyzed using gas chromatography, RT-qPCR and other research methods. Correlation analysis revealed a reciprocal relationship among rumen microflora–VFAs-hepatic gluconeogenesis in Tibetan sheep at different altitudes. Among the microbiota, Ruminococcus flavefaciens (R. flavefaciens), Ruminococcus albus (R. albus), Fibrobactersuccinogenes and Ruminobacter amylophilus (R. amylophilus) were significantly correlated with propionic acid (p < 0.05), while propionic acid was significantly correlated with the transport genes monocarboxylate transporter 4 (MCT4) and anion exchanger 2 (AE2) (p < 0.05). Propionic acid was significantly correlated with key enzymes such as pyruvate carboxylase, phosphoenolpyruvic acid carboxylase and glucose (Glu) in the gluconeogenesis pathway (p < 0.05). Additionally, the expressions of these genes were significantly correlated with those of the related genes, namely, forkhead box protein O1 (FOXO1) and mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2) (p < 0.05). The results showed that rumen microbiota densities differed at different altitudes, and the metabolically produced VFA contents differed, which led to adaptive changes in the key enzyme activities of gluconeogenesis and the expressions of related genes.
Antineoplastic Effect of ALK Inhibitor Crizotinib in Primary Human Anaplastic Thyroid Cancer Cells with STRN–ALK Fusion In Vitro
Authors: Ferrari Silvia Martina , Ragusa Francesca , Elia Giusy , Mazzi Valeria , Balestri Eugenia , Botrini Chiara , Rugani Licia , Patrizio Armando , Piaggi Simona , La Motta Concettina , Ulisse Salvatore , Virili Camilla , Antonelli Alessandro , Fallahi Poupak
Published: June 2024

Anaplastic thyroid cancer (ATC) is one of the deadliest human cancers and represents <2% of thyroid carcinomas. A therapeutic target for ATC is represented by anaplastic lymphoma kinase (ALK) rearrangements, involved in tumor growth. Crizotinib is an oral small-molecule tyrosine kinase inhibitor of the ALK, MET, and ROS1 kinases, approved in ALK-positive non-small cell lung cancer. Until now, the effect of crizotinib in “primary human ATC cells” (pATCs) with transforming striatin (STRN)–ALK fusion has not been reported in the literature. In this study, we aimed to obtain pATCs with STRN–ALK in vitro and evaluate the in vitro antineoplastic action of crizotinib. Thyroid surgical samples were obtained from 12 ATC patients and 6 controls (who had undergone parathyroidectomy). A total of 10/12 pATC cultures were obtained, 2 of which with transforming STRN–ALK fusion (17%). Crizotinib inhibited proliferation, migration, and invasion and increased apoptosis in 3/10 pATC cultures (2 of which with/1 without STRN–ALK), particularly in those with STRN–ALK. Moreover, crizotinib significantly inhibited the proliferation of AF cells (a continuous cell line obtained from primary ATC cells). In conclusion, the antineoplastic activity of crizotinib has been shown in human pATCs (with STRN–ALK) in preclinical studies in vitro, opening the way to future clinical evaluation in these patients.
Genome-Wide Identification, Expression and Response to Estrogen of Vitellogenin Gene Family in Sichuan Bream (Sinibrama taeniatus)
Authors: Zhao Zhe , Peng Li , Zhao Qiang , Wang Zhijian
Published: June 2024

To enhance our understanding of teleost reproductive physiology, we identified six Sichuan bream (Sinibrama taeniatus) vitellogenin genes (vtg1-6) and characterized their sequence structures. We categorized them into type Ⅰ (vtg1,4,5 and 6), type Ⅱ (vtg2) and type Ⅲ (vtg3) based on differences in their subdomain structure. The promoter sequence of vtgs has multiple estrogen response elements, and their abundance appears to correlate with the responsiveness of vtg gene expression to estrogen. Gene expression analyses revealed that the vitellogenesis of Sichuan bream involves both heterosynthesis and autosynthesis pathways, with the dominant pathway originating from the liver. The drug treatment experiments revealed that 17β-estradiol (E2) tightly regulated the level of vtg mRNA in the liver. Feeding fish with a diet containing 100 μg/g E2 for three weeks significantly induced vtg gene expression and ovarian development, leading to an earlier onset of vitellogenesis. Additionally, it was observed that the initiation of vtg transcription required E2 binding to its receptor, a process primarily mediated by estrogen receptor alpha in Sichuan bream. The findings of this study provide novel insights into the molecular information of the vitellogenin gene family in teleosts, thereby contributing to the regulation of gonadal development in farmed fish.
Programmed Cell Death Ligand 1 (PD-L1) Immunohistochemical Expression in Advanced Urothelial Bladder Carcinoma: An Updated Review with Clinical and Pathological Implications
Authors: Germanà Emanuela , Pepe Ludovica , Pizzimenti Cristina , Ballato Mariagiovanna , Pierconti Francesco , Tuccari Giovanni , Ieni Antonio , Giuffrè Giuseppe , Fadda Guido , Fiorentino Vincenzo , Martini Maurizio
Published: June 2024

The management of advanced bladder carcinoma involves a multidisciplinary approach, but the prognosis remains poor for many patients. The immune system plays a crucial role in this disease, influencing both tumor development and response to treatment, and exploiting the immune system against the tumor can be a valuable strategy to destroy neoplastic cells. This is the biological principle underlying Bacillus Calmette–Guérin (BCG) use and, more recently, immune checkpoint inhibitors (ICIs), like PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) inhibitors. In fact, one of the best studied immune checkpoints is represented by the PD-1/PD-L1 axis, which is a well-known immune escape system adopted by neoplastic bladder cells. PD-L1 expression has been associated with a higher pathologic stage and has shown prognostic value in bladder carcinoma. Interestingly, high-grade bladder cancers tend to express higher levels of PD-1 and PD-L1, suggesting a potential role of such an axis in mediating disease progression. Immunotherapy with PD-1 and PD-L1 inhibitors has therefore emerged as a valuable treatment option and has shown efficacy in advanced bladder cancer patients, with high PD-L1 expression levels associated with better treatment responses. Our review aims to provide a comprehensive overview of the role of PD-L1 in advanced bladder cancer, focusing on its implications for treatment decisions and the prediction of treatment response. Overall, our work aims to contribute to the understanding of PD-L1 as a predictive biomarker and highlight its role in shaping therapeutic approaches for advanced bladder cancer.
Onion (Allium cepa L.) Flavonoid Extract Ameliorates Osteoporosis in Rats Facilitating Osteoblast Proliferation and Differentiation in MG-63 Cells and Inhibiting RANKL-Induced Osteoclastogenesis in RAW 264.7 Cells
Authors: Zhang Danyang , Wang Xiaoyu , Sun Kezhuo , Guo Jianli , Zhao Jia , Dong Yuesheng , Bao Yongming
Published: June 2024

Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables, fruits, beans, and cereals, have been reported for their anti-osteoporotic properties. Onion is a commonly consumed vegetable rich in flavonoids with diverse pharmacological activities. In this study, the trabecular structure was enhanced and bone mineral density (BMD) exhibited a twofold increase following oral administration of onion flavonoid extract (OFE). The levels of estradiol (E2), calcium (Ca), and phosphorus (P) in serum were significantly increased in ovariectomized (OVX) rats, with effects equal to alendronate sodium (ALN). Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) levels in rat serum were reduced by 35.7% and 36.9%, respectively, compared to the OVX group. In addition, the effects of OFE on bone health were assessed using human osteoblast-like cells MG-63 and osteoclast precursor RAW 264.7 cells in vitro as well. Proliferation and mineralization of MG-63 cells were promoted by OFE treatment, along with increased ALP activity and mRNA expression of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL). Additionally, RANKL-induced osteoclastogenesis and osteoclast activity were inhibited by OFE treatment through decreased TRAP activity and down-regulation of mRNA expression-related enzymes in RAW 264.7 cells. Overall findings suggest that OFE holds promise as a natural functional component for alleviating osteoporosis.
Machine Learning-Based Etiologic Subtyping of Ischemic Stroke Using Circulating Exosomal microRNAs
Authors: Bang Ji Hoon , Kim Eun Hee , Kim Hyung Jun , Chung Jong-Won , Seo Woo-Keun , Kim Gyeong-Moon , Lee Dong-Ho , Kim Heewon , Bang Oh Young
Published: June 2024

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.
Unique Splicing of Lrp5 in the Brain: A New Player in Neurodevelopment and Brain Maturation
Authors: Luquero Aureli , Pimentel Noelia , Vilahur Gemma , Badimon Lina , Borrell-Pages Maria
Published: June 2024

Low-density lipoprotein receptor-related protein 5 (LRP5) is a constitutively expressed receptor with observed roles in bone homeostasis, retinal development, and cardiac metabolism. However, the function of LRP5 in the brain remains unexplored. This study investigates LRP5’s role in the central nervous system by conducting an extensive analysis using RNA-seq tools and in silico assessments. Two protein-coding Lrp5 transcripts are expressed in mice: full-length Lrp5-201 and a truncated form encoded by Lrp5-202. Wt mice express Lrp5-201 in the liver and brain and do not express the truncated form. Lrp5−/− mice express Lrp5-202 in the liver and brain and do not express Lrp5-201 in the liver. Interestingly, Lrp5−/− mouse brains show full-length Lrp5-201 expression, suggesting that LRP5 has a role in preserving brain function during development. Functional gene enrichment analysis on RNA-seq unveils dysregulated expression of genes associated with neuronal differentiation and synapse formation in the brains of Lrp5−/− mice compared to Wt mice. Furthermore, Gene Set Enrichment Analysis highlights downregulated expression of genes involved in retinol and linoleic acid metabolism in Lrp5−/− mouse brains. Tissue-specific alternative splicing of Lrp5 in Lrp5−/− mice supports that the expression of LRP5 in the brain is needed for the correct synthesis of vitamins and fatty acids, and it is indispensable for correct brain development.
The PD-1/PD-L1 Gateway: Peripheral Immune Regulation in the Pathogenesis of Endometriosis
Authors: Sobstyl Małgorzata , Mertowska Paulina , Mertowski Sebastian , Zaborek-Łyczba Monika , Dudziński Dominik , Polak Grzegorz , Grywalska Ewelina
Published: June 2024

Endometriosis is a chronic inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, causing pain and infertility. Despite the rather unclear etiopathogenesis, recent studies suggest the involvement of the immune system in the development and progression of endometriosis. The role of the PD-1/PD-L1 axis in the modulation of the immune response in this disease seems to be particularly interesting. This preliminary study aimed to investigate the expression of PD-1 and PD-L1 on T and B lymphocytes in peripheral blood in patients with endometriosis to assess their potential impact on disease progression. Our study involved peripheral blood samples from 80 patients diagnosed with endometriosis and 20 healthy women as a control group were analyzed. Flow cytometry was used to assess the expression of PD-1 and PD-L1 on T and B lymphocytes, and enzyme-linked immunosorbent assays were used to assess their soluble forms in serum and peritoneal fluid.in our research we observe significantly higher expression of PD-1 and PD-L1 on T and B lymphocytes was found in patients with endometriosis compared to the control group. Higher expression of both tested molecules correlated with the stage of endometriosis. The results of our preliminary studies indicate a potential role of the PD-1/PD-L1 axis in the modulation of the immune response in endometriosis. Modified expression of these proteins may contribute to immune evasion by ectopic tissues, supporting their survival and proliferation. These findings suggest that targeting PD-1/PD-L1 could be explored as a therapeutic option for the treatment of endometriosis, though further research with larger sample sizes is necessary to confirm these results and clarify the role of PD-1/PD-L1 in the pathogenesis of the disease.
Combined Central and Peripheral Demyelination (CCPD) Associated with MOG Antibodies: Report of Four New Cases and Narrative Review of the Literature
Authors: Papadopoulou Marianna , Tzanetakos Dimitrios , Moschovos Christos , Korona Anastasia , Vartzelis George , Voudris Konstantinos , Fanouraki Stella , Dimitriadou Evangelia-Makrina , Papadimas Georgios , Tzartos John S. , Giannopoulos Sotirios , Tsivgoulis Georgios
Published: June 2024

Background/Objectives: Myelin oligodendrocyte glycoprotein (MOG) is exclusively expressed in the central nervous system (CNS) and is found on the outer surface of oligodendrocytes. Antibodies to MOG are associated with CNS demyelination, whereas peripheral nervous system (PNS) demyelination is seldom reported to be related to MOG-IgG. Methods: The database of patients seen in our neurological academic center was searched for MOG-IgG seropositivity and concomitant demyelinating polyneuropathy. For the purpose of the review, in March 2024, we searched for case reports and case series in the following databases: PubMed, Scopus, Cochrane, and ScienceDirect. Inclusion criteria were MOG-IgG seropositivity and demyelinating polyneuropathy. Exclusion criteria were type of publication other than case reports and case series, unconfirmed diagnosis of demyelinating polyneuropathy, and other diseases causing demyelination in either the CNS or PNS. Critical appraisal of the selected case reports and case series was realized by JBI. Results: Four new cases were identified with MOG-IgG and confirmed demyelinating polyneuropathy. This review identified 22 cases that have been published since 2018. Clinical, imaging, neurophysiological, and immunological characteristics, as well as treatment options and outcomes are presented and compared to those of other cases with combined central and peripheral demyelination (CCPD). Conclusions: The pathogenetic mechanism is unclear; thus, different hypotheses are discussed. New case reporting and large cohort studies will help further the exploration of the underlying mechanism and guide more effective therapeutic interventions.
Clinical Characteristics of Cutaneous Pain in Psoriasis
Authors: Kotewicz Magdalena , Krajewski Piotr K. , Jaworek Andrzej K. , Szepietowski Jacek C.
Published: June 2024

Background: Psoriasis is a common inflammatory disease that is often associated with itch and pain. This study aimed to evaluate the clinical characteristics of skin pain among patients with psoriasis. Materials: A total of 106 patients diagnosed with psoriasis were included in the study (34% female; mean age 42.1 ± 13.0 years). Disease severity was assessed using the Psoriasis Area and Severity Index (PASI). Itch severity was evaluated using the numeric rating scale (NRS) and 4-Item Itch Score (4IIS). The intensity of skin pain was measured through the NRS, short-form McGill pain questionnaire (SF-MPQ), visual analog scale (VAS), and Douleur Neuropathique-4 questionnaire (DN4). Results: In the past week, 84.9% of psoriasis patients reported itch, while 50% of them reported skin pain. The average NRS for itch was 4.52 ± 2.88 points, and the 4IIS yielded a mean score of 6.79 ± 4.37 points. In terms of the intensity of cutaneous pain, the mean NRS was 2.42 ± 2.96 points; the SF-MPQ score averaged 4.84 ± 7.51 points; and the VAS score was 1.92 ± 2.65 points. Furthermore, 17% of adult psoriasis patients reported neuropathic pain. In 84.9% of the participants, skin pain was concurrent with areas affected by itch, while 18.9% of patients exhibited cutaneous pain encompassing all itchy areas. The pain NRS demonstrated significant correlations with the SF-MPQ (r = 0.531, p < 0.001), VAS (r = 0.779, p < 0.001), itch NRS (r = 0.551, p < 0.001), and 4IIS (r = 0.569, p < 0.001). No association was found between the pain NRS and PASI or disease duration. Conclusions: Skin pain of mild intensity and itch of moderate intensity are prevalent symptoms in psoriasis patients. Strong correlations between skin pain and itch can be explained by the process of neurogenic inflammation.
Prognostic Role of OX40, LAG-3, TIM-3 and PD-L1 Expression in Bone and Soft Tissue Sarcomas
Authors: Kurt İnci Bediz , Acar Elif , Gürler Fatih , İlhan Ayşegül , Yıldız Fatih , Ardıç Fisun , Öksüzoğlu Berna , Özdemir Nuriye , Özet Ahmet , Esendağlı Güldal , Yazıcı Ozan
Published: June 2024

Introduction: The current study aims to evaluate the OX40, TIM-3, LAG-3, and PD-L1 targeted pathways in the regulation of T-cell activity in sarcoma patients to determine their relationship with overall survival (OS). Method: This study included one hundred and eleven patients with bone and soft tissue sarcoma diagnosed in two centers between 2010 and 2020. OX40, LAG-3, TIM-3 and PD-L1 expression levels were evaluated immunohistochemically from pathology preparations. Results: PD-L1 staining was detected in tumor cells, OX40, LAG-3, TIM-3 staining was detected in inflammatory cells in tumor tissue. In univariate analysis, no significant relationship was found between OX40, TIM-3, LAG-3, and PD-L1 staining and overall survival (respectively: p = 0.12, p = 0.49, p = 0.31, p = 0.95). When grade and stage at diagnosis, which were found to be significant in univariate analysis, along with OX-40, TIM-3, LAG-3, and PD-L1, were evaluated in multivariate analysis, a positive effect of OX-40 staining on overall survival was determined (p = 0.009). Considering the correlation between PDL-1 and OX40, TIM-3, and LAG-3 staining, a significant positive correlation was found between PDL-1 and TIM-3 and LAG-3 staining (respectively; p = 0.002, p = 0.001). Conclusions: There was no significant relationship between the PDL-1 staining percentage of tumor cells and OX40, TIM-3, and LAG-3 staining in inflammatory cells with the OS of sarcoma patients. However, detecting a significant positive correlation between PDL-1 staining and TIM-3 and LAG-3 staining also holds promise for finding effective targetable combination therapies that can prolong survival in sarcoma patients in the future.
Effects of Exercise Rehabilitation on Cardiorespiratory Fitness in Long-COVID-19 Survivors: A Meta-Analysis
Authors: Nantakool Sothida , Sa-nguanmoo Piangkwan , Konghakote Supatcha , Chuatrakoon Busaba
Published: June 2024

Background: Poor cardiorespiratory fitness poses the highest risk of mortality. Long-COVID-19 survivors exhibit a reduced cardiorespiratory fitness (CRF). While exercise rehabilitation, such as cardiopulmonary exercise, is used for long-COVID-19 survivors, the effects of exercise on CRF in this population remain inconclusive. In this study, we aim to systematically summarise and synthesise whether exercise rehabilitation improves CRF among long-COVID-19 survivors. Methods: A comprehensive search was performed through PubMed, CINAHL, Embase, Scopus, and the Cochrane Library (since their inception to November 2023) and study reference lists. Studies presenting the effects of exercise rehabilitation on CRF (peak oxygen consumption (VO2peak) and six-minute walk distance (6MWD)) in long-COVID-19 survivors were identified. The standardised mean difference (SMD), mean difference (MD), and 95% confidence interval (CI) were used for analyses. The certainty of evidence was measured using a Grading of Recommendation Assessment, Development and Evaluation approach. Results: Twelve eligible studies (five RCTs and seven non-RCTs) with 682 participants were analysed. The meta-analysis showed significantly improved 6MWDs (MD 76.47, 95% CI 59.19–93.71, low certainty) and significantly greater 6MWDs (SMD 0.85, 95% CI 0.11–1.59, very low certainty) in the exercise rehabilitation group compared to the control group. A significantly improved 6MWD was found in subgroups of young to middle-aged adults and subgroups of patients who undertook aerobic exercise combined with resistance and respiratory exercise and centre-based training programs. Conclusions: Exercise rehabilitation is effective for improving CRF, as measured by the 6MWD in long-COVID-19 survivors. Improvements are likely to be more pronounced in specific subgroups of young to middle-aged adults and patients undertaking aerobic exercise combined with resistance and respiratory exercise and centre-based training programs. However, recommendations for clinical practice are limited due to the very low evidence certainty.
Raghib Syndrome and Pulmonary Arterial Hypertension in a Pediatric Patient: Case Report and Literature Review
Authors: Gozar Liliana , Săsăran Maria Oana , Cosma Marius Cătălin , Toma Daniela , Nan Andreea Georgiana , Gozar Horea
Published: June 2024

Background: Raghib syndrome is a rare malformation complex consisting of the drainage of the left superior vena cava (LSVC) into the left atrium, ostial atresia of the coronary sinus and an atrial septal defect (ASD). Case Report: This report aims to present the case of a child newly diagnosed with Raghib syndrome, complicated by pulmonary arterial hypertension, and to review previously published cases with the same diagnosis. A six-year-old female patient presented with signs and symptoms of heart failure (Ross III), reduced exercise tolerance and severe delay in stature and ponderal development. The imagistic work-up included echocardiography, followed by computer tomography (CT) and magnetic resonance imaging (MRI), through which a diagnosis of Raghib syndrome was established, complicated by pulmonary hypertension. As in other cases presented in the literature, MRI allowed for an accurate diagnosis, detecting the absent coronary sinus. The decision regarding the surgical closure of the ASD was made, with the patient having a favorable clinical evolution but with the persistence of elevated pulmonary artery pressure, for which Sildenafil therapy was instituted. Conclusions: The malformation complex consisting of an atrial septal defect, ostium atresia of the coronary sinus, uncovered coronary sinus, and persistent left superior vena cava, as identified through multiple imagistic investigations, was suggestive of the rare diagnosis of Raghib syndrome in this case. Among the limited number of cases of Raghib syndrome available in the literature, the present case is distinguished by the severity of the pulmonary artery hypertension at a very young age and in the absence of other concurrent cardiac malformations.
Low Magnetic Field Induced Extrinsic Strains in Multifunctional Particulate Composites: An Interrupted Mechanical Strengthening in 3D-Printed Nanocomposites
Authors: Mucolli Andiol , Midmer Alden , Manolesos Marinos , Aldosari Salem , Lira Cristian , Yazdani Nezhad Hamed
Published: June 2024

The current paper reports on the quantification of the effect of magnetic fields on the mechanical performance of ferromagnetic nanocomposites in situ during basic standard tensile testing. The research investigates altering the basic mechanical properties (modulus and strength) via the application of a contact-less magnetic field as a primary attempt for a future composites strengthening mechanism. The nanocomposite specimens were fabricated using filament-based 3D printing and were comprised of ferromagnetic nanoparticle-embedded thermoplastic polymers. The nanoparticles were iron particles dispersed at 21 wt.% (10.2 Vol.%) inside a polylactic acid (PLA) polymer, characterised utilising optical microscopy and 3D X-ray computed tomography. The magnetic field was stationary and produced using permanent neodymium round-shaped magnets available at two field strengths below 1 Tesla. The 3D printing was a MakerBot Replicator machine operating based upon a fused deposition method, which utilised 1.75 mm-diameter filaments made of iron particle-based PLA composites. The magnetic field-equipped tensile tests were accompanied by a real-time digital image correlation technique for localized strain measurements across the specimens at a 10-micron pixel resolution. It was observed that the lateral magnetic field induces a slight Poisson effect on the development of extrinsic strain across the length of the tensile specimens. However, the effect reasonably interferes with the evolution of strain fields via the introduction of localised compressive strains attributed to accumulated magnetic polarisation at the magnetic particles on an extrinsic scale. The theory overestimated the moduli by a factor of approximately 3.1. To enhance the accuracy of its solutions for 3D-printed specimens, it is necessary to incorporate pore considerations into the theoretical derivations. Additionally, a modest 10% increase in ultimate tensile strength was observed during tensile loading. This finding suggests that field-assisted strengthening can be effective for as-received 3D-printed magnetic composites in their solidified state, provided that the material and field are optimally designed and implemented. This approach could propose a viable method for remote field tailoring to strengthen the material by mitigating defects induced during the 3D printing process.
Effect of Bivalves’ Sand Burial Capacity on Predation in the Invasive Blue Crab, Callinectes sapidus
Authors: Prado Patricia , Gairin Ignasi , Falco Silvia
Published: June 2024

In the Ebro Delta (Catalonia, Spain), the abundance of burrowing bivalves has dramatically decreased, with the blue crab, Callinectes sapidus, being blamed by shellfish collectors. Trends from 2010 evidence a decrease in the capture of clams (Ruditapes spp.) before 2016 (start of blue crab fisheries), although a further decline in both clams and cockles (Cerastoderma glaucum) occurred in 2018. In contrast, captures of razor clams (Ensis siliqua) have increased by 3.6-fold since 2016. Predation risk for these taxa, with contrasting burrowing capacities (1.7 ± 0.3 cm, 0.4 ± 0.2 cm, and 26.3 ± 0.1 cm, respectively), was assessed using predation preference (N = 5 tanks; 5 individuals of each species) and no-choice experiments (N = 5 tanks; 15 individuals of the same taxa) in the absence and presence of sand. The results showed that, in the absence of sand, razor clams were fully preyed upon in 24 h, clams in 96 h, and cockles reached 60% after 144 h. Conversely, when sand was present, only 4% of razor clams were predated, while clams and cockles reached 60–100% in 120–144 h. The no-choice results featured similar patterns, depending on substrate availability. Overall, clams and cockles appear to be greatly vulnerable to blue crab predation, whereas razor clams may escape thanks to their deeper burrowing capacity.