bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Etiology in Pelvic Organ Prolapse: Role of Connective Tissue Homeostasis, Hormone Metabolism, and Oxidative Stress
Authors: Jiang Wenxuan , Cheung Rachel Yau Kar , Chung Cheuk Yan , Chan Symphorosa Shing Chee , Choy Kwong Wai
Published: December 2024

Background: Pelvic organ prolapse (POP) has become a common health problem among the aging population and affects an increasing number of elderly women worldwide. Studies within family and twin pairs provided strong evidence for the contribution of genetic factors to POP. Given the incomplete penetrance, polygenic traits, and small effect sizes of each variant in complex diseases, it is not always easy to evaluate the genetic susceptibility and molecular mechanisms involved in POP. Objectives: This review intends to comprehensively summarize the current studies on genetic variants associated with POP. Methods: We performed a comprehensive review to summarize the genetic findings from genome-linkage studies, genome-wide association studies, candidate association studies, and gene expression analyses. Results: We summarized genetic variants associated with connective tissue homeostasis, hormone metabolism, and oxidative stress, which were potentially related to the pathophysiology of POP. We also reviewed the limited polygenic risk score (PRS) studies generated for each individual’s genetic risk stratification and its integration into clinical risk factors for disease prediction. Conclusions: This pooled analysis provides moderate epidemiological credibility for associations of these genetic variants with POP to bridge the gap between genetic research and clinical medicine towards understanding the genetic etiology of POP. It also highlights the potential of PRS as a risk prediction model.
Cutaneous Kaposi’s Sarcoma Following Long-Term Infliximab Treatment in a Patient with HIV-Negative Antibiotic-Dependent Chronic Pouchitis: Considerations on an Exceptional Finding
Authors: Pellegrino Raffaele , Palladino Giovanna , Pagliuca Francesca , Lucà Stefano , Federico Alessandro , Gravina Antonietta Gerarda
Published: December 2024

In managing ulcerative colitis (UC), anti-tumour necrosis factor (TNF) agents are among the primary choices. Evidence suggests anti-TNF does not significantly increase malignancy risk (apart from lymphoma and melanoma), though uncertainties persist due to inconsistent long-term data. Kaposi’s sarcoma (KS), induced by human herpesvirus type-8 (HHV-8), is a multifocal neoplasm linked to immunosuppressive therapies, primarily affecting the skin and gastrointestinal tract. KS cases during anti-TNF therapy for UC are anecdotal. We report a rare occurrence of KS in the setting of the long-term use of the standard maintenance dose of infliximab (initiated in 2010) in a 56-year-old male patient with UC diagnosed in 2001. The patient underwent restorative proctocolectomy with ileal J-pouch-anal anastomosis in 2002 and subsequently developed chronic antibiotic-dependent pouchitis. Given the secondary loss of response to infliximab, a switch to vedolizumab was performed. In April 2024, the patient reported the presence of a skin lesion on the right leg. Following surgery, a rhomboid-shaped skin area was removed, encompassing the irregular, greyish KS lesion. The histopathological analysis confirmed the diagnosis of patch-like KS. We continued vedolizumab due to its gut-selective profile. The patient is in clinical remission and under dermatological follow-up with no lesion recurrence.
Evaluating Adverse Drug Reactions, Their Reporting Rates and Their Impact on Attitudes Toward Pharmacotherapy Among Female Patients with Schizophrenia: Insights and Implications from a Cross-Sectional Study
Authors: Bukić Josipa , Herceg Dora , Modun Darko , Krce Ivana , Leskur Dario , Durdov Toni , Herceg Miroslav , Šešelja Perišin Ana , Rušić Doris
Published: December 2024

Background/Objectives: Schizophrenia is a chronic psychiatric disorder usually managed with antipsychotics, which can cause adverse drug reactions (ADRs) that may impact patients’ attitudes toward their treatment, as well as treatment adherence. This study aimed to assess the influence of ADRs and other factors on treatment attitudes among female patients with schizophrenia. Methods: A cross-sectional study was conducted at the Vrapče Psychiatry Clinic with 109 female schizophrenia patients. The DAI-10 (Drug Attitude Inventory) questionnaire was used to assess attitudes toward treatment. Data on their demographic details, pharmacotherapy, ADR occurrence and ADR reporting rates were collected. Multiple regression analyses were used to identify predictors of DAI-10 scores. Results: Patients using more medications and those experiencing ADRs had lower DAI-10 scores, indicating less favorable attitudes (F (2, 106) = 7.364, p = 0.001, R2 = 0.105). ADRs, primarily extrapyramidal symptoms and weight gain, were reported by 43.1% of patients; however, only one patient formally reported them. First-generation antipsychotics were associated with a higher prevalence of ADRs (χ2 = 4.969, df = 1, p = 0.022). Conclusion: Negative experiences with ADRs significantly impact patients’ attitudes and adherence. Low ADR reporting rates highlight the need for better pharmacovigilance education. Enhancing patient awareness may foster more positive attitudes and adherence, potentially improving patient outcomes.
Towards a Thriving Workplace: A Feasibility Study on Mindfulness and the Mediterranean Lifestyle for Corporate Wellness
Authors: Christodoulou Efstratios , Poutli Eleni , Andreou Demetriana , Laoutari Sotiria , Athanasiou Fani , Kourkoutas Yiannis , Koutelidakis Antonios E.
Published: December 2024

Background/Objectives: This study explores the potential of integrating mindfulness and the Mediterranean lifestyle into corporate wellness programs to enhance workplace well-being. Methods: A survey of 485 employees from Greece and Cyprus examined how mindfulness, resilience, adherence to the Mediterranean lifestyle, and work ability are connected. Results: Pearson correlation analysis showed statistically significant positive relationships between mindfulness, resilience, and work ability (p < 0.001 and p < 0.001, respectively). Mindfulness was associated with higher job satisfaction (p < 0.001) and was a significant predictor of good (OR = 1.112, 95% CI: 1.043–1.186, p = 0.001) and excellent (OR = 1.163, 95% CI: 1.087–1.245, p < 0.001) work ability, while adherence to the Mediterranean lifestyle had a lower yet significant positive correlation with resilience (p < 0.01) and work ability (p < 0.05). Differences in wellness across job sectors were observed: employees in health and retail sectors had lower resilience, work ability, and mindfulness compared to those in manufacturing, technology, education, and services. Notably, 78% of participants expressed interest in future wellness programs, favoring a combination of online and onsite formats. Conclusions: These findings suggest that mindfulness and the Mediterranean lifestyle can enhance employee well-being and productivity, but sector-specific strategies may be necessary to address unique challenges. Practical applications include tailoring interventions to meet the needs of employees in sectors with lower wellness scores. Future research should investigate the long-term benefits of such programs across diverse industries and employee groups.
Diagnostic Value of the Alveolar–Arterial Oxygen Gradient in Pulmonary Embolism: A Cross-Sectional Study
Authors: Maslac Ana , Juric Petricevic Slavica , Vukovic Miro , Skopljanac Ivan
Published: December 2024

Background/Objectives: Pulmonary embolism (PE) is a potentially serious condition characterized by the blockage of blood vessels in the lungs, often presenting significant diagnostic challenges due to its non-specific symptoms. This study aimed to evaluate the utility of the alveolar–arterial (A-a) oxygen gradient as a diagnostic tool for PE, hypothesizing that it could enhance early detection when combined with other clinical markers. Methods: We retrospectively analyzed 168 patients at the University Hospital Center Split. This study correlated A-a gradients with PE confirmed by CT pulmonary angiography. Key clinical and biochemical markers, including heart rate, C-reactive protein (CRP), pro-brain natriuretic peptide (NT-proBNP), D-dimer, high-sensitivity troponin (hs-troponin), and arterial oxygen pressure (PaO2), were assessed. Results: Our findings revealed that patients with PE had significantly higher A-a gradients than those without PE. The observed-to-expected ratio for the A-a gradient was notably increased in the PE group. Additionally, patients with PE exhibited elevated heart rate, CRP, NT-proBNP, D-dimer, and hs-troponin levels, while PaO2 levels were notably lower. Conclusions: This study demonstrates that an elevated A-a gradient reflects the severity of gas exchange impairment in PE. The results suggest that early diagnosis of PE may be improved by incorporating A-a gradient analysis alongside other clinical markers, potentially leading to more effective and timely interventions.
Genome-Wide Identification of the ABC Gene Family in Rosaceae and Its Evolution and Expression in Response to Valsa Canker
Authors: Du Chenglong , Yu Hongqiang , Hu Huanhuan , Dou Zhiqi , Zuo Cunwu , Niu Junqiang
Published: December 2024

The ATP-binding cassette (ABC) transporter family plays a critical role in plant growth, development, and disease resistance. However, the evolution and functional characteristics of the ABC gene family in Rosaceae species have not been fully studied. In this study, we performed the first whole-genome identification, as well as an evolutionary analysis and comparative analysis of ABC genes in Rosaceae plants. We identified 3037 ABC genes in 20 plant species, classifying them into eight subfamilies. Comparative analysis revealed significant variations in family size and expansion patterns among species, suggesting adaptive evolution. Tandem duplication (TD: where genes are duplicated in sequence) and whole-genome duplication (WGD: duplication of the entire genome) were identified as the primary drivers of ABC family expansion. In pears, gene pairs produced by WGD underwent purifying selection. Gene ontology (GO) enrichment analysis indicated the involvement of ABC proteins in transmembrane transport and signal transduction pathways. Under Valsa pyri infection, most ABC genes were upregulated in the early stages, highlighting the role of ABCG genes in pathogen response. A weighted gene co-expression network analysis (WGCNA) identified five key ABCG genes potentially involved in pathogen resistance regulation. Our findings provide insights into the evolutionary adaptability of the ABC gene family and their potential applications in plant disease defense.
Mechanism of Exogenous Silicon in Enhancing Cold Stress Tolerance in Solanum lycopersicum L. Seedlings: Insights from Resistance and Quality Indicators
Authors: Zhang Fan , Zhao Yihong , Zhang Yuanbo , Shi Yu , Hou Leiping , Khan Abid , Zhang Ruixing , Zhang Yi
Published: December 2024

Environmental stress, notably the exposure to low temperatures during the early developmental stages of seedlings, has been identified as a critical determinant impacting the yield and quality of tomato crops cultivated in greenhouses. Silicon (Si), recognized as a beneficial element, is posited to mitigate the adverse effects of such stress on plant physiology. This study explores whether exogenous Si fertilizer can effectively alleviate the stress of low temperature and cold damage on tomato plant growth, fruit yield, and quality. Tomato plants were placed under low temperature conditions (6 °C at night, daily average temperature 15 °C), with normal temperature conditions as the control (below 16 °C at night, daily average temperature 28 °C), and two different concentrations of nano Si and ionic Si (50 mg·L−1 and 200 mg·L−1) were sprayed on the leaves, with an equivalent amount of deionized water as the control, for a total of 10 treatments. Relevant indexes were measured to investigate the effects of exogenous Si on tomato resistance, yield, and quality under low-temperature stress. The results show that compared with the control treatment, the plant height, stem diameter, and fresh weight of above-ground and underground parts of tomato seedlings decreased significantly by 46.52%, 42.53%, 28.81%, and 28.97%, respectively, after 15 days of low-temperature stress (p < 0.05), and in order to resist low temperature, the activity of antioxidant enzymes and the content of osmotic adjustment substances were up-regulated in seedlings. Ultimately, low-temperature stress inhibited the morphological growth, nutritional quality, and yield of fruits. Both concentrations of Si application can promote the growth and biomass accumulation of tomato plants under low temperature conditions. Moreover, it significantly ameliorated the osmotic adjustment and antioxidant capacity of the plants, thereby alleviating the low-temperature stress. Under low-temperature stress, 50 mg L−1 ionic Si was the most effective for increasing tomato yield per plant, which was significantly increased by 22.44% compared with the control treatment (p < 0.05). Consequently, the study advocates for the application of 50 mg·L−1 ionic Si fertilizer as a strategy to mitigate the impact of low-temperature stress on tomato plants. Furthermore, the use of nano Si fertilizer has been demonstrated to exert a significant influence on enhancing both the yield and quality of tomatoes, with a 50 mg·L−1 concentration of nano Si fertilizer leading to a notable increase in yield by 20.15% under normal temperature conditions (p < 0.05). These findings are intended to furnish a theoretical foundation and practical direction for advancing research aimed at combating the detrimental effects of low-temperature stress in the context of protected vegetable cultivation.
A Scoping Review of the Current Knowledge of the Social Determinants of Health and Infectious Diseases (Specifically COVID-19, Tuberculosis, and H1N1 Influenza) in Canadian Arctic Indigenous Communities
Authors: Kolahdooz Fariba , Jang Se Lim , Deck Sarah , Ilkiw David , Omoro Gertrude , Rautio Arja , Pirkola Sami , Møller Helle , Ferguson Gary , Evengård Birgitta , Mantla-Look Lianne , DeLancey Debbie , Corriveau André , Irlbacher-Fox Stephanie , Wagg Adrian , Roache Cindy , Rittenbach Katherine , Conter Henry J. , Falk Ryan , Sharma Sangita
Published: December 2024

Social determinants of health (SDHs) and the impact of colonization can make Canadian Arctic Indigenous communities susceptible to infectious diseases, including the coronavirus disease 2019 (COVID-19). This scoping review followed the PRISMA guidelines for scoping reviews and studied what is known about selected pandemics (COVID-19, tuberculosis, and H1N1 influenza) and SDHs (healthcare accessibility, food insecurity, mental health, cultural continuity, housing, community infrastructure, and socioeconomic status (SES)) for Canadian Arctic Indigenous communities. Original studies published in English and French up to October 2024 were located in databases (PubMed, Medline, and CINAHL), AlterNative: An International Journal of Indigenous Peoples, and through reference tracking. We included 118 studies: 6 relating to COVID-19, 5 to influenza, 5 to TB, 27 to food insecurity, 26 to healthcare access, 22 to mental health, 9 to SES, 8 to housing, 7 to cultural continuity, and 3 to community infrastructure. SDHs affecting Indigenous individuals include food insecurity, limited healthcare access, mental health challenges, low SES, suboptimal housing, and limited cultural continuity. These findings are relevant to other Arctic regions. It is crucial to understand how SDHs impact the health of Arctic communities and to utilize this information to inform policy and practice decisions for pandemic prevention, management, and treatment. Many SDHs pose challenges for preventing and managing infectious diseases.
Change Detection and Incremental Updates for Multi-Source Road Networks Considering Topological Consistency
Authors: Wang Xiaodong , Zhao Dongbao , Li Xingze , Jia Nan , Guo Li
Published: December 2024

Vector road networks are vital components of intelligent transportation systems and electronic navigation maps. There is a pressing need for efficient and rapid dynamic updates for road network data. In this paper, we propose a series of methods designed specifically for geometric change detection and the topological consistency updating of multi-source vector road networks without relying on complicated road network matching. For geometric change detection, we employ buffer analysis to compare various sources of vector road networks, differentiating between newly added, deleted, and unchanged road features. Furthermore, we utilize road shape similarity analysis to detect and recognize partial matching relationships between different road network sources. For incremental updates, we define topology consistency and propose three distinct methods for merging road nodes, aiming to preserve the topological integrity of the road network to the greatest extent possible. To address geometric conflicts and topological inconsistencies, we present a fusion and update method specifically tailored for partially matched road features. In order to verify the proposed methods, a road central line network with a scale of 1:10000 from the official institution is employed to geometrically update the commercial navigation road network of a similar scale in the remote area. The experiment results indicate that our method achieves an impressive 91.7% automation rate in detecting geometric changes for road features. For the remaining 8.3% of road features, our method provides suggestions on potential geometric changes, albeit necessitating manual verification and assessment. In terms of the incremental updating of the road network, approximately 89.2% of the data can be seamlessly updated automatically using our methods, while a minor 10.8% requires manual intervention for road updates. Collectively, our methods expedite the updating cycle of vector road network data and facilitate the seamless sharing and integrated utilization of multi-source road network data.
Positive Effect of Elevated Thawing Rate for Cryopreservation of Human Ovarian Tissue: Transcriptomic Analysis of Fresh and Cryopreserved Cells
Authors: Kong Qingduo , Todorov Plamen , Pei Cheng , Isachenko Evgenia , Rahimi Gohar , Mallmann-Gottschalk Nina , Isachenko Volodimir
Published: December 2024

Ovarian tissue cryopreservation has been gradually applied. It is essential to elucidate the differences between cryopreserved and fresh ovarian tissue and to refine cryopreservation protocols for improved outcomes. To explore the transcriptomic differences between fresh ovarian tissue and tissue cryopreserved with an elevated thawing rate. Ovarian tissue samples were collected and cryopreserved (frozen and thawed) following RNA sequencing and histological evaluation. Three groups were formed: fresh tissue (Group 1), frozen tissue after quick thawing at 100 °C (Group 2), and frozen tissue after slow thawing at 37 °C (Group 3). KEGG analysis showed that in comparison with Group 1, DEGs in Group 2 were mainly enriched in the cortisol synthesis and ovarian steroidogenesis pathways, and DEGs in the cells of Group 3 were mainly enriched in the ovarian steroidogenesis pathway. GO analysis showed that compared to cells of Group 2, DEGs in Group 3 were primarily enriched in the SRP-dependent co-translational protein targeting pathway and co-translational protein targeting to the membrane. The results were formulated with a minimal difference in the histological evaluation of cells after quick and slow thawed tissue. Cryopreservation of ovarian tissue by the described method does not decrease follicle production but downregulates the ovarian steroidogenesis pathway, reducing estrogen and progesterone secretion. The quick thawing of ovarian tissue increases the proliferation and apoptosis pathways of cells.
A Role of Inflammation in Charcot–Marie–Tooth Disorders—In a Perspective of Treatment?
Authors: Kamińska Joanna , Kochański Andrzej
Published: December 2024

Despite the fact that there are published case reports and model work providing evidence of inflammation in Charcot–Marie–Tooth disorders (CMTs), in clinical practice, CMT and inflammatory neuropathies are always classified as two separate groups of disorders. This sharp separation of chronic neuropathies into two groups has serious clinical implications. As a consequence, the patients harboring CMT mutations are practically excluded from pharmacological anti-inflammatory treatments. In this review, we present that neuropathological studies of peripheral nerves taken from some patients representing familial aggregation of CMTs revealed the presence of inflammation within the nerves. This shows that neurodegeneration resulting from germline mutations and the inflammatory process are not mutually exclusive. We also point to reports demonstrating that, at the clinical level, a positive response to anti-inflammatory therapy was observed in some patients diagnosed with CMTs, confirming the role of the inflammatory component in CMT. We narrowed a group of more than 100 genes whose mutations were found in CMT-affected patients to the seven most common (MPZ, PMP22, GJB1, SEPT9, LITAF, FIG4, and GDAP1) as being linked to the coexistence of hereditary and inflammatory neuropathy. We listed studies of mouse models supporting the idea of the presence of an inflammatory process in some CMTs and studies demonstrating at the cellular level the presence of an inflammatory response. In the following, we discuss the possible molecular basis of some neuropathies involving neurodegenerative and inflammatory processes at both the clinical and morphological levels. Finally, we discuss the prospect of a therapeutic approach using immunomodulation in some patients affected by CMTs.
Methods and Models for Studying Mycobacterium tuberculosis in Respiratory Infections
Authors: Franco Caterina , Rezzani Rita
Published: December 2024

Respiratory infections, including tuberculosis, constitute a major global health challenge. Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the leading causes of mortality worldwide. The disease’s complexity is attributed to Mtb’s capacity to persist in latent states, evade host immune defenses, and develop resistance to antimicrobial treatments, posing significant challenges for diagnosis and therapy. Traditional models, such as animal studies and two-dimensional (2D) in vitro systems, often fail to accurately recapitulate human-specific immune processes, particularly the formation of granulomas—a defining feature of tubercular infection. These limitations underscore the need for more physiologically relevant models to study TB pathogenesis. Emerging three-dimensional (3D) in vitro systems, including organoids and lung-on-chip platforms, offer innovative approaches to mimic the structural and functional complexity of the human lung. These models enable the recreation of key aspects of the tubercular granulomas, such as cellular interactions, oxygen gradients, and nutrient limitations, thereby providing deeper insights into Mtb pathogenesis. This review aims to elucidate the advantages of 3D in vitro systems in bridging the translational gap between traditional experimental approaches and clinical applications. Particular emphasis is placed on their potential to address challenges related to genetic variability in both the host and pathogen, thereby advancing tubercular research and therapeutic development.
Synthesis of Pyrazole-Based Inhibitors of the Bacterial Enzyme N-Succinyl-l,l-2,6-Diaminopimelic Acid Desuccinylase (DapE) as Potential Antibiotics
Authors: DiPuma Thomas , Kelley Emma H. , Thabthimthong Teerana , Bland Alayna , Konczak Katherine , Torma Katherine J. , Mohammad Thahani S. Habeeb , Olsen Kenneth W. , Becker Daniel P.
Published: December 2024

Based on the inhibitory potencies from earlier reported tetrazole thioether analogs, we now describe the synthesis and inhibition of pyrazole-based inhibitors of N-succinyl-l,l-2,6-diaminopimelic acid desuccinylase (DapE) from Haemophilus influenzae (HiDapE). The most potent pyrazole analog 7d bears an aminopyridine amide with an IC50 of 17.9 ± 8.0 μM, and the single enantiomer of ɑ-methyl analog 7q has an IC50 of 18.8 µM, with potency residing in the (R)-enantiomer. Thermal shift revealed strong stabilization upon binding inhibitor (R)-7q with Tm = 50.2 °C and a Ki of 17.3 ± 2.8 μM. Enzyme kinetic experiments confirm competitive inhibition, and docking reveals key active site interactions.
Novel FANCI and RAD54B Variants and the Observed Clinical Outcomes in a Hungarian Melanoma Cohort
Authors: Bokor Barbara Anna , Abdolreza Aliasgari , Kaptás Flóra , Pál Margit , Battyani Zita , Széll Márta , Nagy Nikoletta
Published: December 2024

Accumulating evidence suggests that inherited melanoma is not rare and approx. one in seven individuals with melanoma has clinically relevant hereditable cancer-predisposing and/or -susceptibility variant(s). Concerning its germline genetic background, genetic screening aims to identify either variants of predisposing genes with high penetrance or variants of susceptibility genes with medium or low penetrance. However, less attention is paid to genetic testing of germline variants of genes influencing patients’ survival outcomes or enhancing the design of new therapies. We aimed to investigate whether the germline genetic background of a Hungarian melanoma cohort (n = 17) contains any pathogenic or likely pathogenic variants of the BRCA2, POLE, WRN, FANCI, PALB2, and RAD54B genes and if the presence of these variants correlate with the clinical findings of the patients, including the advanced stage of melanoma, poor prognosis, and poor survival. We identified three novel variants in the FANCI gene and one novel variant in the RAD54B gene. We detected rapid disease progression, unfavorable outcome, and therapeutic resistance in the patient carrying the likely pathogenic FANCI variant. Our study highlights the importance of screening germline variants of genes influencing melanoma progression, therapy resistance, and survival of patients.
Evaluation of Spirulina platensis as a Feed Additive in Low-Protein Diets of Broilers
Authors: Yalçınkaya Hüseyin , Yalçın Sakine , Ramay Muhammad Shazaib , Onbaşılar Esin Ebru , Bakır Buket , Elibol Fatma Kübra Erbay , Yalçın Suzan , Shehata Awad A. , Basiouni Shereen
Published: December 2024

Spirulina platensis is a natural antioxidant product that has the ability to improve the performance of poultry. Therefore, the present study aimed to evaluate the effect of using Spirulina platensis as a feed additive in broiler diets. A total of 252 daily male Ross 308 chicks were randomly assigned to six groups. There were two different protein groups: one was at the catalog protein value, and the other was reduced by 10%. Spirulina platensis at 0, 0.1, and 0.2% was added to each protein group. The trial lasted 41 days. Reducing the protein level by 10% had a negative impact on the performance of the chicks. However, Spirulina platensis supplementation had a positive effect on the feed conversion ratio, reduced the oxidative stress index in the chicks’ liver and meat, increased the total antioxidant status and antioxidant enzyme activities, improved the villus height, serum IgG, and some bone parameters, and reduced the serum triglyceride concentration. The carcass yield, visceral organ weight percentages, total phenolic content, and malondialdehyde (MDA) level in the thigh meat and some serum biochemical parameters were not affected by the usage of Spirulina platensis. In conclusion, 0.1% Spirulina platensis could be a feasible feed additive in low-protein diets due to eliciting an improved performance, antioxidant status, and immune response in broilers.
Integrated Transcriptomic and Metabolomic Analysis of G. hirsutum and G. barbadense Responses to Verticillium Wilt Infection
Authors: Xing Baoguang , Li Pengtao , Li Yanfang , Cui Bingkai , Sun Zhihao , Chen Yu , Zhang Shaoliang , Liu Qiankun , Zhang Aiming , Hao Liuan , Du Xue , Liu Xiaoyan , Wu Bei , Peng Renhai , Hu Shoulin
Published: December 2024

Verticillium wilt (VW) caused by Verticillium dahliae (Vd) is a devastating fungal cotton disease characterized by high pathogenicity, widespread distribution, and frequent variation. It leads to significant losses in both the yield and quality of cotton. Identifying key non-synonymous single nucleotide polymorphism (SNP) markers and crucial genes associated with VW resistance in Gossypium hirsutum and Gossypium barbadense, and subsequently breeding new disease-resistant varieties, are essential for VW management. Here, we sequenced the transcriptome and metabolome of roots of TM-1 (G. hirsutum) and Hai7124 (G. barbadense) after 0, 1, and 2 days of V991 inoculation. Transcriptome analysis identified a total of 72,752 genes, with 5814 differentially expressed genes (DEGs) determined through multiple group comparisons. KEGG enrichment analysis revealed that the key pathways enriched by DEGs obtained from both longitudinal and transverse comparisons contained the glutathione metabolism pathway. Metabolome analysis identified 995 metabolites, and 22 differentially accumulated metabolites (DAMs), which were correlated to pathways including glutathione metabolism, degradation of valine, leucine, and isoleucine, and biosynthesis of terpenoids, alkaloids, pyridine, and piperidine. The conjoint analysis of transcriptomic and metabolomic sequencing revealed DAMs and DEGs associated with the glutathione metabolism pathway, and the key candidate gene GH_D11G2329 (glutathione S-transferase, GSTF8) potentially associated with cotton response to VW infection was selected. These findings establish a basis for investigating the mechanisms underlying the cotton plant’s resistance to VW.
The α1- and β1-Subunits of Nitric Oxide-Sensitive Guanylyl Cyclase in Pericytes of Healthy Human Dental Pulp
Authors: Korkmaz Yüksel , Pryymachuk Galyna , Schroeter Mechthild M. , Puladi Behrus , Piekarek Nadin , Appel Sarah , Bloch Wilhelm , Lackmann Jan-Wilm , Deschner James , Friebe Andreas
Published: December 2024

Nitric oxide-sensitive guanylyl cyclase (NO-GC) is a heterodimeric enzyme with an α- and a β-subunit. In its active form as an α1β1-heterodimer, NO-GC produces cyclic guanosine-3′,5′-monophophate (cGMP) to regulate vasodilation and proliferation of vascular smooth muscle cells (VSMCs). In contrast to VSMCs, only a few studies reported on the expression of the NO-GC α1β1-heterodimer in human pericytes. Since NO-GC is a marker for platelet-derived growth factor-β (PDGFRβ)-positive pericytes, we investigated whether NO-GC is expressed in its active α1β1-heterodimer in pericytes of healthy human dental pulp. In our previous studies, we developed and validated an antibody against the α1-subunit of human NO-GC. Here, we developed a new antibody against the β1-subunit of human NO-GC and validated it by immunoblot, mass spectrometry, and immunohistochemistry on tissue samples from humans and NO-GC knockout (GCKO) mice. Using both antibodies, we detected α1- and β1-subunits of NO-GC in pericytes of pre-capillary arterioles, capillaries, and post-capillary venules in dental pulp of decalcified and non-decalcified human molars. We concluded that NO-GC as an active α1β1-heterodimer may be involved in the regulation of vascular permeability, vascular stability, organ homeostasis, and organ regeneration in healthy human dental pulp.
The Role of Vimentin Peptide Citrullination in the Structure and Dynamics of HLA-DRB1 Rheumatoid Arthritis Risk-Associated Alleles
Authors: Alves Cinthia C. , Lewis Jaila , Antunes Dinler A. , Donadi Eduardo A.
Published: December 2024

Citrullination, a post-translational modification (PTM), plays a critical role in rheumatoid arthritis (RA) by triggering immune responses to citrullinated self-antigens. Some HLA-DRB1 genes encode molecules with the shared epitope (QKRAA/QRRAA) sequence in the peptide-binding groove which preferentially presents citrulline-modified peptides, like vimentin, that intensifies the immune response in RA. In this study, we used computational approaches to evaluate intermolecular interactions between vimentin peptide-ligands (with/without PTM) and HLA-DRB1 alleles associated with a significantly increased risk for RA development. Crystal structures for HLA-DRB1*04:01, *04:04, and *04:05 bound to citrullinated peptides (PDB ID: 4MCY, 4MD5, 6BIR) were retrieved from the Protein Data Bank and non-citrullinated 3D structures were generated by mutating citrulline to arginine. The pHLA complexes were submitted to four rounds (50 ns each) of molecular dynamic simulations (MD) with Gromacs v.2022. Our results show that citrulline strengthens the interaction between vimentin and the HLA-DRB1 molecules, therefore impacting both the peptide affinity to the HLAs and pHLA stability; it also induces more intermolecular hydrogen bond formation during MD in the pHLA. Citrulline prevents repulsion between amino acid 71β and the P4-residue of native vimentin. Thus, vimentin citrullination seems to affect pHLA binding and dynamics, which may influence RA-related immune responses.
The Interplay Between High Cumulative Doses of Radioactive Iodine and Type 2 Diabetes Mellitus: A Complex Cardiovascular Challenge
Authors: Stanciu Adina Elena , Bolovan Madalina Lucica , Zamfir-Chiru-Anton Adina , Voiosu Catalina , Dabla Pradeep Kumar , Stanciu Marcel Marian , Serdarevic Nafija , Gherghe Mirela
Published: December 2024

Starting from the metabolic profile of type 2 diabetes mellitus (T2DM), we hypothesized that the mechanisms of ¹³¹I-induced cardiotoxicity differ between patients diagnosed with differentiated thyroid cancer (DTC) with/without T2DM, with metformin potentially acting as a cardioprotective agent by mitigating inflammation in patients with T2DM. To address this hypothesis, we quantified, using ELISA, the serum concentration of several key biomarkers that reflect cardiac injury (NT-proBNP, NT-proANP, ST2/IL-33R, and cTn I) in 74 female patients with DTC/−T2DM and 25 with DTC/+T2DM treated with metformin. All patients received a cumulative oral dose of 131I exceeding 150 mCi (5.55 GBq) over approximately 53 months. Our results showed the following: (i) In DTC/−T2DM patients, high-cumulative 131I doses promote a pro-inflammatory state that accelerates the development of cardiotoxicity. Monitoring NT-proBNP, ST2/IL-33R, and cTn I in these patients may help identify those at risk of developing cardiac complications. (ii) In patients with DTC/+T2DM, high-cumulative 131I doses lead to the release of NT-proANP (r = 0.63), which signals that the atria are under significant stress. (iii) In patients with DTC/+T2DM, metformin suppresses inflammation, leading to a dose-dependent reduction in cTn I (r = −0.59). Monitoring cTn I and NT-proANP, and considering the use of metformin as part of the therapeutic strategy, could help manage cardiotoxicity in T2DM patients undergoing 131I therapy.
Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions
Authors: Capelletti Martina Maria , Montini Orsola , Ruini Emilio , Tettamanti Sarah , Savino Angela Maria , Sarno Jolanda
Published: December 2024

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Understanding the metabolic diversities among cancer cells and their surrounding environments is therefore essential in unravelling the complexities of leukaemia and improving therapeutic strategies. Here, we describe the currently available methodologies and approaches to addressing the dynamic heterogeneity of leukaemia progression. In the second section, we focus on metabolic leukaemic vulnerabilities in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). Lastly, we provide a comprehensive overview of the most interesting clinical trials designed to target these metabolic dependencies, highlighting their potential to advance therapeutic strategies in leukaemia treatment. The integration of multi-omics data for cancer identification with the metabolic states of tumour cells will enable a comprehensive “micro-to-macro” approach for the refinement of clinical practices and delivery of personalised therapies.
Unveiling the Movement of RanBP1 During the Cell Cycle and Its Interaction with a Cyclin-Dependent Kinase (CDK) in Plants
Authors: Thomé Vanessa , Ferreira Pedro B. , Lubini Greice , Nogueira Fernanda M. , Strini Edward J. , Pinoti Vitor F. , Cruz Joelma O. , San Martin Juca A. B. , Quiapim Andréa C. , daSilva Luis L. P. , Goldman Maria Helena S.
Published: December 2024

In the Nicotiana tabacum flower development study, we identified SCI1 (Stigma/style Cell-cycle Inhibitor 1), a regulator of cell proliferation. SCI1 interacts with NtCDKG;2 (N. tabacum Cyclin-Dependent Kinase G;2), a homolog of human CDK11, which is responsible for RanGTP-dependent microtubule stabilization, regulating spindle assembly rate. In a Y2H screening of a cDNA library using NtCDKG;2 as bait, a RanBP1 (Ran-Binding Protein 1) was revealed as its interaction partner. RanBP1 is an essential regulatory protein of the RanGTPase system, contributing to the formation of the Ran gradient, which modulates different important cellular processes. RanBP1 is crucial in the nuclear import/export machinery during interphase and spindle checkpoint formation during cell division. These processes are well studied in animals, but very little is known about them in plants. We confirmed NtCDKG;2 and NtRanBP1 interaction by pairwise Y2H and characterized the localization of both proteins during plant cell division. We demonstrated the presence of NtRanBP1 in the cytoplasm during interphase and its nuclear arrest at mitosis onset. Meanwhile, we showed that NtCDKG;2 is localized in the mitotic spindle during cell division, indicating an analogous function to the human CDK11. We propose that the phosphorylation of the nuclear export signal at RanBP1 by NtCDKG;2 may be responsible for the reported nuclear arrest.
Investigation of Active Components of Meconopsis integrifolia (Maxim.) Franch in Mitigating Non-Alcoholic Fatty Liver Disease
Authors: Lu Qiqin , La Majia , Wang Ziyang , Huang Jiaomei , Zhu Jiahui , Zhang Dejun
Published: December 2024

Nonalcoholic fatty liver disease (NAFLD) has rapidly emerged as the most prevalent chronic liver disease globally, representing a significant and escalating public health challenge. Meconopsis integrifolia (Maxim.) Franch, a traditional Tibetan medicinal herb used for treating hepatitis, remains largely unexplored regarding its therapeutic potential and active components in combating NAFLD. This study first evaluated the in vitro lipid accumulation inhibitory activity of different extraction fractions of M. integrifolia using a HepG2 cell steatosis model. The ethyl acetate fraction was found to significantly reduce triglyceride (TG) and low-density lipoprotein (LDL) levels, inhibit lipid droplet deposition in HepG2 cells, and promote lipid metabolism balance through modulation of the AMPK/SREPB-1c/PPAR-α signaling pathway. Further analysis utilizing chromatographic techniques and nuclear magnetic resonance spectroscopy (NMR) led to the isolation of 13 compounds from the active ethyl acetate fraction. Notably, compounds 6, 9, 10, 11, 12, and 13 were identified for the first time from this Tibetan herb. In vitro activity assays and molecular docking analyses further confirmed that the compounds Luteolin (1), Quercetin 3-O-[2‴, 6‴-O-diacetyl-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside] (6), and Quercetin 3-O-[2‴-O-acetyl-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside] (8) are potential key components responsible for the NAFLD-ameliorating effects of M. integrifolia. This study highlights the therapeutic potential of M. integrifolia in treating NAFLD and provides a foundation for its further development and application, underscoring its significance in the advanced utilization of traditional Tibetan medicine.
Comparison Between Nano-Hydroxyapatite/Beta-Tricalcium Phosphate Composite and Autogenous Bone Graft in Bone Regeneration Applications: Biochemical Mechanisms and Morphological Analysis
Authors: Brum Igor da Silva , Frigo Lucio , Ribeiro da Silva Jemima Fuentes , Ciambarella Bianca Torres , Nascimento Ana Lucia Rosa , Pereira Mario José dos Santos , Elias Carlos Nelson , de Carvalho Jorge José
Published: December 2024

It was assumed that only autogenous bone had appropriate osteoconductive and osteoindutive properties for bone regeneration, but this assumption has been challenged. Many studies have shown that synthetic biomaterials must be considered as the best choice for guided bone regeneration. The objective of this work is to compare the performances of nanohydroxyapatite/β-tricalcium phosphate (n-HA/β-TCP) composite and autogenous bone grafting in bone regeneration applications. The composite was characterized by scanning electron microscopy (SEM) and used as an allograft in bone defects formed in adult Wistar rats. The bone defects in the dorsal cranium were grafted with autogenous bone on one side and the n-HA/β-TCP composite on the other. Histomorphometry evaluation via different staining methods (Goldner trichrome, PAS, and Sirius red) and TRAP histochemistry were performed. Immunohistomorphometries of OPN, Cathepsin K, TRAP, acid phosphatase, VEGF, NFκ-β, MMP-2, MMP-9, and TGF-β were carried out. The RT-PCR method was also applied to to RANK-L, Osteocalcine, Alcaline Phosphatase, Osterix, and Runx2. The results showed that for all morphometric evaluations with the different staining methods, histochemistry, and immunohistochemistry, VEGF and NFκ-β were higher in the n-HA/β-TCP composite group than in the autogenous bone graft group. The RT-PCR markers were higher in the autogenous bone group than in the n-HA/β-TCP composite group. The n-HA/β-TCP composite exhibited enhanced cell–matrix interactions in bone remodeling, higher adhesion, proliferation, and differentiation, and increased vascularization. These results suggest that the n-HA/β-TCP composite induces faster bone formation than autogenous bone grafting.
Characterization of the Rhizobiome of the Yellow Pitcher Plant (Sarracenia flava) in Wild and Restored Habitats of Virginia
Authors: Lee Bo-Young , Andresen Nikki , Sheridan Phil , Brown Bonnie L.
Published: December 2024

The yellow pitcher plant, Sarracenia flava, is an insectivorous perennial distributed extensively in southeastern North America. In Virginia, it is restricted to a few wetland ecosystems, with only one natural site known to remain. To uncover whether there were microbial differences in the rhizospheres across natural and reintroduced sites of pitcher plant restoration, shotgun metagenome sequencing was undertaken to characterize the microbiomes of the healthy rhizosphere in the last remaining natural stand in Virginia compared to rhizospheres sampled in two restored habitats where pitcher plants were reintroduced and a nearby control habitat without pitcher plants. Statistical analysis showed no significant differences in rhizobiome communities among the natural, reintroduced, and control sites. Comparison of test rhizobiomes with those of other soil types revealed no significant difference in S. flava habitats versus wildland soil types but significant difference from agricultural soils. Indicator species analysis found Pseudomonas was a significantly more abundant genus in the S. flava habitats. The control site was enriched with iron-reducing bacteria compared to the rest of the sites. Further studies based on gene expression could better facilitate an understanding of the role of Pseudomonas in S. flava rhizosphere specific to habitats, which will provide better knowledge for local conservation of this plant.
Allosteric Fluorescent Detection of Saccharides and Biomolecules in Water from a Boronic Acid Functionalized Arene Ruthenium Assembly Hosting Fluorescent Dyes
Authors: Maatouk Alaa , Rossel Thibaud , Therrien Bruno
Published: December 2024

A water-soluble arene ruthenium metalla-rectangle (MR1) functionalized with boronic acid groups was used to host various fluorescent dyes (fluorescein, eosin Y, and erythrosin B). These simple host–guest systems partially quench the natural fluorescence of the dyes, which can be regained in the presence of saccharides, phosphorylated molecules, and other analytes. The intensity of the regained fluorescence is directly linked to the nature of the analyte, and it shows some dose–response relationships with saccharides and phosphorylated molecules that are not compatible with a displacement assay, thus suggesting an allosteric mechanism. Interestingly, when fluorescein is trapped by the metalla-rectangle in the presence of D-fructose, half of the maximum fluorescence intensity is recovered at a fructose concentration of 17.2 ± 4.7 μM, while, for D-glucose, a concentration of 50.6 ± 2.5 μM is required for the same effect. Indeed, all combinations of analyte–host–dye (seven analytes, one host, three dyes) show a unique dose–response relationship in water at pH 8.0. However, in the presence of naphthalene and pyrene, fluorescein⸦MR1 shows a different behavior, acting as an indicator displacement assay with the full recovery of fluorescence. All data were analyzed by unsupervised machine learning technologies (PCA and cluster analysis), suggesting that such systems with multiple analyte–response behaviors are offering new perspectives for the development of highly sensitive, easily tunable, water-soluble, fluorescent-based sensing arrays for biomolecules and other analytes.