bluuebunny/crossref_metadata_2025 huggingface dataset:
Detecting Alu Element Insertion Variant in RP1 Gene Using Whole Genome Sequencing in Patients with Retinitis Pigmentosa
Authors: Kwon Hye-Ji , Lee Beom-Hee , Lee Joo-Yong
Published: September 2024

Background/Objectives: Alu element insertion in the exon 4 of the RP1 gene was newly identified through whole genome sequencing (WGS). This was not detected in previous next-generation sequencing (NGS) analysis. We report three cases of Korean retinitis pigmentosa (RP) patients with compound heterozygous variants including Alu element insertion in the RP1 gene, indicating that Alu element insertion could be a cause of RP; Methods: Among patients diagnosed with RP having variants in the RP1 gene in the Asan Medical Center, WGS was additionally performed for genetically unsolved cases in previous NGS analysis to detect any presence of Alu element insertion. For cases detected to have Alu element insertion in the exon 4 of the RP1 gene, genetic and clinical characteristics were analyzed; Results: Among 16 patients with RP, 3 patients were detected to have Alu element insertion in the RP1 gene. Alu element insertion in the RP1 gene was also detected using WGS. It was revealed to be a pathogenic variant. Therefore, RP1 gene mutation was the confirmed genetic cause of RP for these three cases and genetic counseling was enabled for them; Conclusions: Alu element insertion in the RP1 gene could be a genetic cause of autosomal recessive RP patients with compound heterozygous variants. Through WGS, the identification of this pathogenic variant was possible. Confirmation is needed to check the presence of Alu element insertion in patients with compound heterozygous variants in the RP1 gene.
coiTAD: Detection of Topologically Associating Domains Based on Clustering of Circular Influence Features from Hi-C Data
Authors: Houchens Drew , Chowdhury H. M. A. Mohit , Oluwadare Oluwatosin
Published: September 2024

Background/Objectives: Topologically associating domains (TADs) are key structural units of the genome, playing a crucial role in gene regulation. TAD boundaries are enriched with specific biological markers and have been linked to genetic diseases, making consistent TAD detection essential. However, accurately identifying TADs remains challenging due to the lack of a definitive validation method. This study aims to develop a novel algorithm, termed coiTAD, which introduces an innovative approach for preprocessing Hi-C data to improve TAD prediction. This method employs a proposed “circle of influence” (COI) approach derived from Hi-C contact matrices. Methods: The coiTAD algorithm is based on the creation of novel features derived from the circle of influence in input contact matrices, which are subsequently clustered using the HDBSCAN clustering algorithm. The TADs are extracted from the clustered features based on intra-cluster interactions, thereby providing a more accurate method for identifying TADs. Results: Rigorous tests were conducted using both simulated and real Hi-C datasets. The algorithm’s validation included analysis of boundary proteins such as H3K4me1, RNAPII, and CTCF. coiTAD consistently matched other TAD prediction methods. Conclusions: The coiTAD algorithm represents a novel approach for detecting TADs. At its core, the circle-of-influence methodology introduces an innovative strategy for preparing Hi-C data, enabling the assessment of interaction strengths between genomic regions. This approach facilitates a nuanced analysis that effectively captures structural variations within chromatin. Ultimately, the coiTAD algorithm enhances our understanding of chromatin organization and offers a robust tool for genomic research. The source code for coiTAD is publicly available, and the URL can be found in the Data Availability Statement section.
Experimental Study on the Time-Dependent Resistance of Open-Ended Steel Piles in Sand
Authors: Manthey Sven , Vogt Stefan , Cudmani Roberto , Kidane Mussie
Published: September 2024

Open-ended steel piles are commonly used as the foundation for offshore structures. Numerous model and field tests have demonstrated a time-dependent increase in the resistance of these piles, a phenomenon referred to as pile ageing or pile setup. Additionally, for open-ended steel piles with comparably small diameters, soil plugging enhances the resistance against axial compressive loads. Realistically predicting these effects is necessary for their reliable incorporation into design practice. This contribution presents static compression and tension pile load testing conducted in an experimental pit filled with wet, uniformly graded silica sand. In total, twelve piles (L= 5.5 m, Do= 325 mm) were driven into homogeneously compacted sand using a pneumatic impact hammer. Firstly, static compression pile load testing was executed at various times after installation. Subsequently, static tension pile load tests were carried out. The results of the static compression pile load tests indicate that the compressive resistance doubles over an ageing period of 64 weeks. The experimental investigations of the effect of soil plugging showed marginal soil plugging during pile installation, but a significant influence of the soil plug on the compressive resistance.
Insights into Pharmacists’ Participation in Professional Certification Programs in Saudi Arabia
Authors: Alhuzli Ammar Y. , Alzahrani Mohammed B. , Althobaiti Ahmed J. , Alshammari Abdullah S. , Alharbi Adnan , Elrggal Mahmoud , Alorfi Nasser M. , Bahamdain Foud O. , Alnemari Walaa , Alrashed Mohammed , Alotaibi Abdulmalik S. , Alnuhait Mohammed A.
Published: September 2024

Introduction: Professional certification programs play a crucial role in helping pharmacists develop specialized skills and establish their expertise in the field. This study explores how pharmacists in Saudi Arabia engage with these programs by examining their levels of awareness, attitudes, and participation. It also identifies the key barriers and motivators that influence their decision to pursue certification. Methods: An online survey was conducted among pharmacists in Saudi Arabia to assess participants’ knowledge of certification programs, their perceived benefits, the actual participation rates, and their preferences regarding certification areas and assessment methods. Results: Out of 394 participating pharmacists, around 47% had never participated in a professional certification program, and about 27% of our sample were unaware of such programs in Saudi Arabia. Financial constraints and a lack of awareness were noted as the primary barriers to participation. Almost 55% showed an interest in Clinical Pharmacy Specialties certification, while 54% were inclined toward Pharmacy Management and Leadership certifications. A preference for practical assessments in certification programs was suggested by 55% of participants. Conclusions: This study highlights a significant need for increased awareness and accessibility to professional certification programs among pharmacists in Saudi Arabia. Addressing participation barriers is vital to foster professional development and meet the healthcare sector’s evolving demands in Saudi Arabia.
The Effects of the Expansion of Dental Care Coverage for the Elderly
Authors: Zhao Yang , Kim Beomsoo
Published: September 2024

Background: Expanding dental care coverage for the elderly is globally recommended but not widely implemented due to its high costs and intangible benefits. Methods: This study examined the impact of such an expansion in Korea using the imputation-based method proposed by Borusyak et al. We analyzed data from the Korea National Health and Nutrition Examination Survey (2007–2019) on dental service utilization and chewing ability among older adults. Results: The policy resulted in a 13.5% increase in partial denture use and a 60.5% increase in dental implants among those aged 65 and above. These changes corresponded with reductions in severe chewing difficulty by 23.3% and 13.0%, respectively. No significant changes were observed in full denture use. The price elasticity of demand for partial dentures and dental implants was estimated to be −0.19 and −0.86, respectively. Conclusions: These findings underscore the critical role of affordability in enhancing the utilization of dental implants among the elderly and highlight the importance of appropriately expanding dental insurance coverage to improve oral health outcomes in this population.
Cost-Effectiveness Analysis of Pneumococcal Vaccines in the Pediatric Population: A Systematic Review
Authors: Vo Nam Xuan , Pham Huong Lai , Bui Uyen My , Ho Han Tue , Bui Tien Thuy
Published: September 2024

Objectives: Pneumococcal disease, caused by Streptococcus pneumoniae, is the leading cause of mortality in children worldwide. The tremendous direct cost of hospital admissions and significant indirect costs from productivity loss contribute considerably to its economic burden, with vaccination being the only efficient protection against the illness. Our study aims to summarize the cost-effectiveness of the pneumococcal conjugate vaccine (PCV) implemented in the pediatric population. Methods: Employing the online databases PubMed, Embase, and Medline, we looked for economic evaluations from 2018 until March 2024. The Incremental Cost-Effectiveness Ratios (ICER) and Quality-Adjusted Life Years (QALY) were the primary outcomes for measuring the cost-effectiveness of PCVs. A 28-item CHEERS 2022 checklist was applied to assess the quality of the collected studies. Results: Of the 16 papers found, 9/16 discussed the lower-valent vaccines (PCV13, PCV10) and 7/16 examined the higher-valent vaccines (PCV20, PCV15). PCV13 and PCV10 involved greater costs and generated more QALY compared to no vaccination. Both PCV15 and PCV20 averted substantial healthcare costs and yielded greater quality of life than PCV13. Additionally, PCV20 was a dominant strategy compared to PCV15. Conclusions: Utilizing PCV13 is a very cost-effective option compared to not getting vaccinated. Transitioning from PCV13 to PCV20 would result in higher QALY gain and more cost-saving than switching to PCV15.
Modified Oral Health Assessment Tool (M-OHAT) for Residential Aged Care: A Co-Design Protocol
Authors: Ferris Laura J. , Ludlow Kristiana , Walker Nicole , Georgiou Andrew , Henry Julie D. , Lopez Silva Claudia , Ha Diep H. , Stormon Nicole , Walsh Laurence J. , Ivanovski Saso , Sexton Christopher , Silveira Schuch Helena , Tuffaha Haitham , Zamora Angelique , Pritchard Lyndal , Do Loc G.
Published: September 2024

Background: Older adults in residential aged care facilities (RACFs) experience disproportionate levels of poor oral health relative to other groups in the general population, affecting their physical and mental wellbeing. The Oral Health Assessment Tool (OHAT) is a validated and widely used dental assessment tool; however, recent systematic reviews have identified shortcomings with respect to its measurement properties. Objective: The objective of this protocol is to provide a detailed overview of a multidisciplinary qualitative study that aims to (a) co-design and develop a modified OHAT for RACFs and (b) inform the development of an OHAT training package and implementation strategies. Methods: This study will utilize a co-design methodology with aged care residents, caregivers, staff members, and health professionals. The co-design workshops will: (1) investigate the barriers to and enablers of optimal oral healthcare in RACFs; and (2) co-design a modified version of the Oral Health Assessment Tool and a referral to treatment pathway that is appropriate for use in RACFs. The co-design workshops will facilitate group discussion and involve interactive activities using, for example, mind mapping and Sticky Notes. Qualitative data (transcripts and artefacts from co-design activities) will be analyzed in NVivo using an inductive codebook thematic analysis, specifically a template analysis. Conclusion: The findings of this study will inform a modified OHAT (M-OHAT), as well as future study phases regarding training and implementation strategies. It is expected that the M-OHAT will have enhanced usability and relevance to RACFs, facilitating the identification of poor oral health and timely referral to dental treatment.
A Rare Case of Primary Bone Follicular Lymphoma with Multiple Osteolytic Lesions: A Case Report and Review of the Literature
Authors: Togni Chiara , La Verde Giacinto , Pelliccia Sabrina , Bianchi Maria Paola , Di Napoli Arianna , Lanzolla Tiziana , Zerunian Marta , Laghi Andrea , Maiorana Gianluca , Taglietti Ambra , Tafuri Agostino
Published: September 2024

Introduction: Primary bone lymphoma (PBL) is a rare clinical entity, accounting for less than 5% of all extranodal non-Hodgkin lymphomas and approximately 5% of primary bone tumors. Diffuse large B-cell lymphoma (DLBCL) is the most common histotype, accounting for about 80% of all PBL cases. Conversely, the incidence of indolent primary bone lymphomas (iPBL) represents less than 1% of all reported PBL cases, and data on these rarer lymphomas are scarce. Drawing on diagnostic criteria developed by the World Health Organization (WHO) and the International Extranodal Lymphoma Study Group (IELSG), we report a rare case of primary bone follicular lymphoma, focusing specifically on the clinical presentation and treatment. Discussion: Additionally, we provide a systematic review of the literature data on this very rare lymphoproliferative entity.
Seismic Vulnerability Assessment of Historic Centers with Two Fast Methods Based on CARTIS Survey Methodology and Fragility Curves
Authors: Cardani Giuliana , Garavaglia Elsa
Published: September 2024

After an earthquake, legislation tends to permit the rapid demolition of damaged buildings, including the built heritage, for safety reasons, as was the case for many small historic centers after the 2016 earthquake in central Italy. A balance should, of course, be struck between safety and preservation. There must be a willingness to engage in continuous interaction with the various bodies involved in post-earthquake management, particularly in the preventive phase of the complex activities regarding the issues of the seismic vulnerability of historic built. The widespread historical built heritage in Italy requires fast and reliable assessment procedures that allow a large-scale evaluation of the vulnerability of historical buildings before a seismic event. To this end, a proposal is presented here for the inverse use of the protocol for the seismic vulnerability survey of historic centers by means of a system called CARTIS form, coordinated since 2015 by the Italian consortium of Seismic and Structural Engineering Laboratories (ReLUIS). This rapid assessment is compared with an equally fast method for constructing fragility curves, based only on the information available in the ReLUIS–CARTIS database, defining the relationship between the probability of reaching a level of loss of structural safety or a vulnerability index as a function of the seismic acceleration PGA and the ground orography. The methodology outlined could be considered to be progress in cultural heritage diagnostics on a large scale, considering cultural heritage to be the diffuse historical residential masonry buildings that form the historic centers.
The Scientific Reference Model—A Methodological Approach in the Hypothetical 3D Reconstruction of Art and Architecture
Authors: Kuroczyński Piotr , Bajena Igor Piotr , Cazzaro Irene
Published: September 2024

Scientific practice relies on the rigorous documentation of procedures, methods, and outcomes, governed by principles like method verification, objectivity, and source disclosure. In the computer-based hypothetical 3D reconstruction of destroyed or never realised art and architecture, adhering to these principles faces challenges due to evolving software, methods, and data types, leading to a lack of standardised documentation and publication practices for 3D models. Consequently, the traceability, accessibility, and sustainability of research outcomes are compromised. Decades after the advent of computer-aided 3D visualisation in cultural heritage, there is a critical need to define applicable methodology and comprehensive documentation standards. Web-based platforms necessitate technical infrastructures and clear scientific methodologies to ensure understandable model creation and sustainable accessibility to 3D research data. The Scientific Reference Model proposes an accessible academic framework for this kind of 3D reconstruction, aiming to facilitate broad adoption. Developed and tested in research projects and educational contexts, this model aims to establish clear, accessible 3D models on the web, serving as foundational references for future research and knowledge dissemination.
Optimizing Biochemical and Phytochemical Attributes in Peaches through Foliar Applications of Silicon and Zinc
Authors: Shah Syed Tanveer , Ahmad Naseer , Basit Abdul , Sajid Muhammad , Jamal Aftab , Saeed Muhammad Farhan , Iqbal Waleed , Seleiman Mahmoud F. , Radicetti Emanuele , Mancinelli Roberto
Published: September 2024

Peach production faces significant pre-harvest challenges, including low moisture, nutrient deficiencies, flower drop, physical damage, and surface discoloration, which can limit yield and fruit quality. To mitigate these issues, the present study hypothesized that foliar applications of silicon and zinc could enhance peach growth, yield, and quality due to their known roles in improving stress tolerance, nutrient uptake, and antioxidant activity. Therefore, this research aimed to identify optimal concentrations of silicon and zinc for quality peach production. Ten-year-old peach trees of uniform size were sprayed with four levels of silicon (0%, 0.1%, 0.2%, and 0.3%) and zinc (0%, 0.25%, 0.50%, and 0.75%) for two consecutive growing seasons, at the berry and pit hardening stages, using a Randomized Complete Block Design (RCBD) with three replications. The averaged data from the two years showed that the pre-harvest foliar application of silicon significantly improved all yield and quality attributes of peaches. The foliar application of silicon at 0.3% notably enhanced fruit growth, yield, and biochemical attributes. Additionally, the highest fruit growth, yield, and quality of peach fruits were observed at the 0.75% zinc concentration. Maximum antioxidant activity, flavonoid content, proline content, and catalase activity were observed in fruits from plants treated with 0.3% silicon, which were statistically on par with 0.2% silicon. However, peroxidase activity was highest at 0.2% silicon. Regarding zinc levels, antioxidant activity, flavonoid content, proline content, and peroxidase activity were highest in fruits treated with 0.75% zinc, while catalase activity was superior when fruits were sprayed with 0.50% zinc. The interaction between silicon and zinc concentrations was found to be non-significant for most parameters, except for titratable acidity, TSS–acid ratio, ascorbic acid content, antioxidant activity, flavonoid content, and peroxidase activity. In conclusion, the foliar application of 0.3% silicon and 0.75% zinc independently enhanced all yield and quality characteristics of peaches. For the agro-climatic conditions of Peshawar, 0.2% silicon and 0.50% zinc are recommended for optimal peach production.
Agronomic, Biochemical, and Physiological Responses to Magnesium (Mg) Application in Tomato (Solanum lycopersicum L.) under Greenhouse Conditions
Authors: Nas Yahya , Kömürkara Zengin Sevil
Published: September 2024

Magnesium fertilization positively impacts various physiological processes in plants, leading to increased yield and fruit quality. In the present study, we determined the effects of the foliar application of magnesium on the yield, fruit quality, fruit biochemical content, and enzyme activity of tomato plants. The study was performed in a plastic greenhouse. The study evaluated magnesium sulfate application through drip irrigation at a single dose of 0.005 kg m2 and foliar application at rates of 0%, 0.25%, 0.5%, and 0.75%. As a consequence, the highest average fruit weight was obtained with the foliar application of 0.50% Mg. In terms of the fruit color’s a* value, the best results were again obtained with the application of 0.50% Mg. Mg applications proportionally increased the leaf chlorophyll content. Similarly, the highest leaf Mg content, the leaf relative water content, the fruits’ malic acid content, and the best fruit juice pH value were determined with the application of 0.75%. On the other hand, the application of 0.25% Mg produced the best results on the leaves’ K, Ca, and Na content, as well as in the fruits’ ascorbic acid content. Significant differences were not found in terms of the effects of the treatments on antioxidant activity, total protein amount, and enzyme activity. The application of 0.50% Mg contributed to the fruit color; 0.75% Mg application contributed to the chlorophyll, pH, and malic acid content; and the application of 0.25% Mg contributed to an increase in ascorbic acid. In conclusion, for greenhouse tomato production, a foliar application of 0.50% Mg is recommended to achieve larger, red-colored fruits. A 0.75% Mg application is suggested for increasing the chlorophyll content, lowering fruit juice pH, and enhancing malic acid content in fruits. A 0.25% Mg application is recommended to increase ascorbic acid content in fruits.
Comparative Analysis of the Effects of Crude Metabolic Extracts of Three Biocontrol Bacteria on Microbial Community Structure Provides a New Strategy for the Biological Control of Apple Replant Disease
Authors: Lv Jinhui , Jiang Weitao , Xu Zihui , Wang Gongshuai , Li Xiaoxuan , Wu Xinyu , Ding Fengxia , Liu Yusong , Chen Xuesen , Yin Chengmiao , Mao Zhiquan
Published: September 2024

The crude metabolic extract from plant biocontrol bacteria plays a very important role in sustainable agricultural production. These extracts help maintain healthy plants and have very important application prospects in biotechnology related to alleviating apple replant disease (ARD). In this study, Bacillus velezensis XC1 (T1), Bacillus amyloliquefaciens QSB-6 (T2), and Lactobacillus reuteri LBR (T3) were examined to characterize the ability of their crude metabolic extracts to alleviate ARD. The high-throughput sequencing data of the soil microbial community structure were analyzed in relation to LBR crude metabolic extracts, and an extensive untargeted metabolomic analysis of UHPLC-Qex active components was performed. Active LC-MS/MS revealed that the main secondary metabolites involved in the biological control exerted by L. reuteri included 3-hydroxypropionaldehyde, extracellular polysaccharides (EPS), p-hydroxybenzoic acid, and azelaic acid. These crude metabolic extracts significantly inhibited the growth of soil pathogenic fungi, reduced the abundance of Fusarium, promoted the abundance of beneficial bacteria such as Pseudomonas, and optimized the soil microbial community structure. Improved modern extraction and purification technologies will be able to offer additional insights into the mechanism of action of these secondary metabolites and enable them to be used in biological preparations to prevent and control ARD in the future, as well as to allow harmful chemical fumigants to be discontinued.
Physicochemical Marker for Determination of Value-Adding Component in Over-Ripe Thai Mango Peels
Authors: Chaiwan Pirawan , Rachtanapun Pornchai , Phimolsiripol Yuthana , Ruksiriwanich Warintorn , Li Chunmei , Luo Lu , Shen Dan , Chung Hsiao-Hang , George David , Tangpao Tibet , Sommano Sarana Rose , Sunanta Piyachat
Published: September 2024

Thailand is a prominent global producer of mangoes, providing a wide range of mango cultivars and dealing with the challenge of managing biomass. Thus, biorefining mango peel to extract valuable components has the potential to reduce organic waste and create a new revenue source for the mango processing sector. This study aims to examine the physiology, physiochemical, and chemical characteristics in peel of nine Thai mango cultivars, along with the relationship between their characteristics. The Thai mango cultivars Mahachanok, Chok anan, and Rad exhibited a yellow appearance, while the other six cultivars appeared yellow-green. However, the firmness of the fruit was directly correlated with the firmness of the pulp. A proximate composition study revealed that the predominant constituent of mango peel was carbohydrates, comprising up to 75% of its composition. This was followed by fibre, which accounted for up to 13%. The Nga mango had the highest levels of total phenolic content (220 mgGAE/g) and total flavonoid content (5.5 mgCE/g). The primary phenolic acids identified in Thai mango peel were epicatechin, caffeic acid, catechin, and gallic acid. The Mahachanok cultivar exhibited the highest antioxidant activity, as determined by the ABTS and DPPH assays, with values of 85.67% and 85.78%, respectively. This study demonstrated the connections between the physiochemical characteristics of mangoes and their chemical compositions in different cultivars, indicating the possibility of choosing particular cultivars for extracting targeted bioactive compounds. The multivariate analyses revealed that there was no correlation between the physiochemical and chemical profiles of mangoes. This study highlights the significance of mango peel as a valuable by-product that has significant environmental and economic ramifications for the mango processing industry.
Role of BraSWEET12 in Regulating Flowering through Sucrose Transport in Flowering Chinese Cabbage
Authors: He Qinqin , He Liming , Feng Zongqin , Liu Yin , Xiao Yunyi , Liu Jinfeng , Han Hanbing , Huang Xinmin
Published: September 2024

We assessed the flowering Chinese cabbage (Brassica rapa var. parachinensis), a specialty vegetable found in southern China. The sugar content of the stem tip is closely related to bolting and flowering. Sugar Will Eventually be Exported Transporters (SWEETs) are bidirectional sugar transporter proteins involved in numerous plant growth and development processes. The expression of BraSWEET12 is positively correlated with sugar content. However, it is unclear whether BraSWEET12 is involved in bolting and flowering. In this study, we identified and characterized BraSWEET12. BraSWEET12 in flowering Chinese cabbage contains 288 amino acids and is located on the cell membrane as a sucrose transporter protein. BraSWEET12 is highly expressed in the petals and stem tips of flowering Chinese cabbage and is upregulated by gibberellin and low temperatures. Overexpression of BraSWEET12 in Arabidopsis can increase sucrose content at the stem tip, upregulate the expression of AtAP1 and AtLFY, and advance the flowering time. Subsequently, our results indicate that BraSWEET12 is involved in sucrose accumulation at the stem tip of flowering Chinese cabbage and plays a crucial role in flowering regulation. These results provide a reference for elucidating the regulatory mechanisms underlying flowering Chinese cabbage bolting and flowering.
Effects of Ethylene Inhibitors on the Long-Term Maintenance of the Embryogenic Callus of Vitis vinifera L.
Authors: Forleo Lucia Rosaria , Basile Teodora , Suriano Bruna , Maggiolini Flavia Angela Maria , D’Amico Margherita , Cardone Maria Francesca , Velasco Riccardo , Bergamini Carlo
Published: September 2024

Vitis vinifera is an important fruit crop which is mainly consumed fresh or used for the production of wine. Genetic improvement programs through New Genomic Techniques (NGTs) aim to develop grapevine varieties resistant to biotic and abiotic stresses or enhancing nutraceutical properties. In order to apply NGTs, maintaining embryogenic calluses from flower tissues is critical. Optimizing culture conditions—pH, gelling agents, temperature, light, growth regulators, and gas composition—is essential for inducing efficient embryogenic responses tailored to each genotype/explant. Ethylene, a pivotal gaseous plant hormone, significantly influences tissue culture by affecting organogenesis and embryogenesis processes in several plants. Modulating ethylene levels shows promise for improving tissue culture vitality. This study evaluates in Vitis vinifera the effects of silver thiosulfate (STS) and salicylic acid (SA) on embryogenic callus growth, specifically investigating their roles in maintaining and inducing embryogenic competence. STS, particularly at 40 µM and 60 µM concentrations, effectively preserved embryogenic competence in Italia and Red Globe calluses, while high SA concentrations showed varied and occasionally adverse effects. At the same time, STS markedly suppressed the non-embryogenic callus growth in recalcitrant variety Italia, potentially increasing the ratio between embryogenic to non-embryogenic calluses development.
The Role of Protein Post-Translational Modifications in Fruit Ripening
Authors: Li Ting , Zeng Jing , Yang Xinquan , Garcia-Caparros Pedro , Duan Xuewu
Published: September 2024

Fruit ripening represents a multifaceted biological process intricately controlled by an array of plant hormones, transcription factors, and epigenetic modifications. These regulatory mechanisms are crucial in determining fruit quality and post-harvest shelf life. Recent advancements in proteomics have shifted the focus toward understanding protein post-translational modifications (PTMs), which play a crucial role in modulating protein function. PTMs enhance protein activity and stability by altering their properties after biosynthesis, thereby adding an additional layer of regulation to the ripening process. This paper provides a comprehensive review of the roles of PTMs, including ubiquitination, phosphorylation, redox modifications, and glycosylation in regulating fruit ripening. Emphasis is placed on the intricate interplay between these PTMs and key regulator factors such as plant hormones, transcriptional mechanisms, and epigenetic modifications. By exploring these interactions, this review seeks to enhance our understanding of the complex regulatory network underlying fruit ripening and to offer novel perspectives on strategies for fruit preservation.
Analytical Techniques for the Authenticity Evaluation of Chokeberry, Blackberry and Raspberry Fruit Wines: Exploring FT-MIR Analysis and Chemometrics
Authors: Petric Ivana Vladimira , Duralija Boris , Leder Renata
Published: September 2024

The modern analytical technique of Fourier-transform mid-infrared spectroscopy (FT-MIR) has found its place in routine wine quality control. It allows rapid and nondestructive analysis, with easy sample preparation and without the need for chemical pretreatment or expensive reagents. The objective of this research was to apply these advantages to fruit wines in order to create a tool for the authentication of fruit wines produced from different fruit species (chokeberry, blackberry, and raspberry). The aim of this work was to establish a chemometric model from FT-MIR spectra and to find a “fingerprint” of specific fruit wines, enabling the classification of fruit wines by plant species. Physicochemical analysis of 111 Croatian fruit wine samples (38 liqueur fruit wines and 73 fruit wines) revealed content levels of the following parameters: alcoholic strength (5.0–15.2% vol.), total dry extract (60.4–253.3 g/L), total sugars (1.2–229.9 g/L), pH (3.13–4.98), total acidity (4.2–18.3 g/L) and volatile acidity (0.2–1.5 g/L). For statistical data processing, spectral ranges between 926 and 1450 cm−1 and between 1801 and 2951 cm−1 were used. The first principal component (PC1) explained 70.4% of the observed variation, and the second component (PC2) explained 16.7%, clearly separating chokeberry fruit wines from blackberry and raspberry fruit wines. Soft Independent Modeling Class Analogy (SIMCA) was performed following the development of a PCA model showing that the chokeberry and blackberry wine samples form clearly separated clusters. Key discriminators for classifying chokeberry vs. blackberry wines were identified at 1157, 1304, and 1435 cm−1, demonstrating high discrimination power (DP 26, 17, and 14, respectively). FT-MIR spectroscopy, in combination with chemometric methods, has shown promising potential for the authenticity assessment of fruit wines.
Correction: Kim et al. Neuroprotective Effect of Statins in a Rat Model of Chronic Ocular Hypertension. Int. J. Mol. Sci. 2021, 22, 12500
Authors: Kim Mi-Lyang , Sung Kyung Rim , Kwon Junki , Choi Go Woon , Shin Jin-A
Published: September 2024

In the original publication [...]
Defects in the Maturation of Mitochondrial Iron–Sulfur Proteins: Biophysical Investigation of the MMDS3 Causing Gly104Cys Variant of IBA57
Authors: Bargagna Beatrice , Staderini Tommaso , Lang Steven H. , Banci Lucia , Camponeschi Francesca
Published: September 2024

Multiple mitochondrial dysfunctions syndrome type 3 (MMDS3) is a rare autosomal recessive mitochondrial leukoencephalopathy caused by biallelic pathogenic variants in the IBA57 gene. The gene protein product, IBA57, has an unknown role in iron–sulfur (Fe-S) cluster biogenesis but is required for the maturation of mitochondrial [4Fe-4S] proteins. To better understand the role of IBA57 in MMDS3, we have investigated the impact of the pathogenic p.Gly104Cys (c.310G > T) variant on the structural and functional properties of IBA57. The Gly104Cys variant has been associated with a severe MMDS3 phenotype in both compound heterozygous and homozygous states, and defects in the activity of mitochondrial respiratory complexes and lipoic acid-dependent enzymes have been demonstrated in the affected patients. Size exclusion chromatography, also coupled to multiple angle light scattering, NMR, circular dichroism, and fluorescence spectroscopy characterization has shown that the Gly104Cys variant does not impair the conversion of the homo-dimeric [2Fe-2S]–ISCA22 complex into the hetero-dimeric IBA57–[2Fe-2S]–ISCA2 but significantly affects the stability of IBA57, in both its isolated form and in complex with ISCA2, thus providing a rationale for the severe MMDS3 phenotype associated with this variant.
Animal Models of Autistic-like Behavior in Rodents: A Scoping Review and Call for a Comprehensive Scoring System
Authors: Ornoy Asher , Echefu Boniface , Becker Maria
Published: September 2024

Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as autism spectrum disorder (ASD) necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior to expected measurable behavioral features in animals. If possible, the severity of the symptoms should also be assessed. Indeed, at least in rodents, adequate neurobehavioral and neurological tests have been developed. Since ASD is characterized by a number of specific behavioral trends with significant severity, animal models of autistic-like behavior have to demonstrate the specific characteristic features, namely impaired social interactions, communication deficits, and restricted, repetitive behavioral patterns, with association to several additional impairments such as somatosensory, motor, and memory impairments. Thus, an appropriate model must show behavioral impairment of a minimal number of neurobehavioral characteristics using an adequate number of behavioral tests. The proper animal models enable the study of ASD-like-behavior from the etiologic, pathogenetic, and therapeutic aspects. From the etiologic aspects, models have been developed by the use of immunogenic substances like polyinosinic-polycytidylic acid (PolyIC), lipopolysaccharide (LPS), and propionic acid, or other well-documented immunogens or pathogens, like Mycobacterium tuberculosis. Another approach is the use of chemicals like valproic acid, polychlorinated biphenyls (PCBs), organophosphate pesticides like chlorpyrifos (CPF), and others. These substances were administered either prenatally, generally after the period of major organogenesis, or, especially in rodents, during early postnatal life. In addition, using modern genetic manipulation methods, genetic models have been created of almost all human genetic diseases that are manifested by autistic-like behavior (i.e., fragile X, Rett syndrome, SHANK gene mutation, neuroligin genes, and others). Ideally, we should not only evaluate the different behavioral modes affected by the ASD-like behavior, but also assess the severity of the behavioral deviations by an appropriate scoring system, as applied to humans. We therefore propose a scoring system for improved assessment of ASD-like behavior in animal models.
Selection and Regulatory Network Analysis of Differential CircRNAs in the Hypothalamus of Goats with High and Low Reproductive Capacity
Authors: Mao Shuaixiang , Wu Cuiying , Feng Guanghang , Li Yaokun , Sun Baoli , Guo Yongqing , Deng Ming , Liu Dewu , Liu Guangbin
Published: September 2024

The objectives of this investigation were to identify differentially expressed circular RNAs (circRNAs) in the hypothalamus of goats with high and low prolificacy and construct a circRNA-mRNA regulatory network to uncover key potential circRNAs that influence goat prolificacy. Transcriptome analysis was performed on hypothalamus samples from low-prolificacy (n = 5) and high-prolificacy (n = 6) Chuanzhong black goats to identify circRNAs that influence prolificacy in these goats. Differential expression analysis identified a total of 205 differentially expressed circRNAs, comprising 100 upregulated and 105 downregulated circRNAs in the high-prolificacy group compared with the low-prolificacy group. Enrichment analysis of these differentially expressed circRNAs indicated significant enrichment in Gene Ontology terms associated with mammalian oogenesis, negative regulation of neurotransmitter secretion, reproductive developmental processes, hormone-mediated signaling pathways, and negative regulation of hormone secretion. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted significant enrichment in the oxytocin signaling pathway, GnRH signaling pathway, and hormone-mediated oocyte maturation. The hypothalamus of low- and high-prolificacy goats contains circular RNAs (circRNAs), including chicirc_063269, chicirc_097731, chicirc_017440, chicirc_049641, chicirc_008429, chicirc_145057, chicirc_030156, chicirc_109497, chicirc_030156, chicirc_176754, and chicirc_193363. Chuanzhong black goats have the potential to influence prolificacy by modulating the release of serum hormones from the hypothalamus. A circRNA-miRNA regulatory network was constructed, which determined that miR-135a, miR-188-3p, miR-101-3p, and miR-128-3p may interact with differentially expressed circRNAs, thereby regulating reproductive capacity through the hypothalamic-pituitary-gonadal axis. The results of this study enhance our knowledge of the molecular mechanisms that regulate prolificacy in Chuanzhong black goats at the hypothalamic level.
Translational Research and Therapies for Neuroprotection and Regeneration of the Optic Nerve and Retina: A Narrative Review
Authors: Oshitari Toshiyuki
Published: September 2024

Most retinal and optic nerve diseases pose significant threats to vision, primarily due to irreversible retinal neuronal cell death, a permanent change, which is a critical factor in their pathogenesis. Conditions such as glaucoma, retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration are the top four leading causes of blindness among the elderly in Japan. While standard treatments—including reduction in intraocular pressure, anti-vascular endothelial growth factor therapies, and retinal photocoagulation—can partially delay disease progression, their therapeutic effects remain limited. To address these shortcomings, a range of neuroprotective and regenerative therapies, aimed at preventing retinal neuronal cell loss, have been extensively studied and increasingly integrated into clinical practice over the last two decades. Several of these neuroprotective therapies have achieved on-label usage worldwide. This narrative review introduces several neuroprotective and regenerative therapies for retinal and optic nerve diseases that have been successfully translated into clinical practice, providing foundational knowledge and success stories that serve as valuable references for researchers in the field.
The MCIB Model: A Novel Theory for Describing the Spatial Heterogeneity of the Tumor Microenvironment
Authors: Guo Minghao , Sun Yinan , Wang Xiaohui , Wang Zikun , Yuan Xun , Chen Xinyi , Yuan Xianglin , Wang Lu
Published: September 2024

The tumor microenvironment (TME) can be regarded as a complex and dynamic microecosystem generated by the interactions of tumor cells, interstitial cells, the extracellular matrix, and their products and plays an important role in the occurrence, progression and metastasis of tumors. In a previous study, we constructed an IEO model (prI-, prE-, and pOst-metastatic niche) according to the chronological sequence of TME development. In this paper, to fill the theoretical gap in spatial heterogeneity in the TME, we defined an MCIB model (Metabolic, Circulatory, Immune, and microBial microenvironment). The MCIB model divides the TME into four subtypes that interact with each other in terms of mechanism, corresponding to the four major links of metabolic reprogramming, vascular remodeling, immune response, and microbial action, providing a new way to assess the TME. The combination of the MCIB model and IEO model comprehensively depicts the spatiotemporal evolution of the TME and can provide a theoretical basis for the combination of clinical targeted therapy, immunotherapy, and other comprehensive treatment modalities for tumors according to the combination and crosstalk of different subtypes in the MCIB model and provide a powerful research paradigm for tumor drug-resistance mechanisms and tumor biological behavior.
Opportunities for Riboswitch Inhibition by Targeting Co-Transcriptional RNA Folding Events
Authors: Stephen Christine , Palmer Danea , Mishanina Tatiana V.
Published: September 2024

Antibiotic resistance is a critical global health concern, causing millions of prolonged bacterial infections every year and straining our healthcare systems. Novel antibiotic strategies are essential to combating this health crisis and bacterial non-coding RNAs are promising targets for new antibiotics. In particular, a class of bacterial non-coding RNAs called riboswitches has attracted significant interest as antibiotic targets. Riboswitches reside in the 5′-untranslated region of an mRNA transcript and tune gene expression levels in cis by binding to a small-molecule ligand. Riboswitches often control expression of essential genes for bacterial survival, making riboswitch inhibitors an exciting prospect for new antibacterials. Synthetic ligand mimics have predominated the search for new riboswitch inhibitors, which are designed based on static structures of a riboswitch’s ligand-sensing aptamer domain or identified by screening a small-molecule library. However, many small-molecule inhibitors that bind an isolated riboswitch aptamer domain with high affinity in vitro lack potency in vivo. Importantly, riboswitches fold and respond to the ligand during active transcription in vivo. This co-transcriptional folding is often not considered during inhibitor design, and may explain the discrepancy between a low Kd in vitro and poor inhibition in vivo. In this review, we cover advances in riboswitch co-transcriptional folding and illustrate how intermediate structures can be targeted by antisense oligonucleotides—an exciting new strategy for riboswitch inhibitor design.
Telomere Reprogramming and Cellular Metabolism: Is There a Link?
Authors: Rubtsova Maria P. , Nikishin Denis A. , Vyssokikh Mikhail Y. , Koriagina Maria S. , Vasiliev Andrey V. , Dontsova Olga A.
Published: September 2024

Telomeres—special DNA–protein structures at the ends of linear eukaryotic chromosomes—define the proliferation potential of cells. Extremely short telomeres promote a DNA damage response and cell death to eliminate cells that may have accumulated mutations after multiple divisions. However, telomere elongation is associated with the increased proliferative potential of specific cell types, such as stem and germ cells. This elongation can be permanent in these cells and is activated temporally during immune response activation and regeneration processes. The activation of telomere lengthening mechanisms is coupled with increased proliferation and the cells’ need for energy and building resources. To obtain the necessary nutrients, cells are capable of finely regulating energy production and consumption, switching between catabolic and anabolic processes. In this review, we focused on the interconnection between metabolism programs and telomere lengthening mechanisms during programmed activation of proliferation, such as in germ cell maturation, early embryonic development, neoplastic lesion growth, and immune response activation. It is generally accepted that telomere disturbance influences biological processes and promotes dysfunctionality. Here, we propose that metabolic conditions within proliferating cells should be involved in regulating telomere lengthening mechanisms, and telomere length may serve as a marker of defects in cellular functionality. We propose that it is possible to reprogram metabolism in order to regulate the telomere length and proliferative activity of cells, which may be important for the development of approaches to regeneration, immune response modulation, and cancer therapy. However, further investigations in this area are necessary to improve the understanding and manipulation of the molecular mechanisms involved in the regulation of proliferation, metabolism, and aging.
The Use of Patient-Derived Organoids in the Study of Molecular Metabolic Adaptation in Breast Cancer
Authors: Glibetic Natalija , Bowman Scott , Skaggs Tia , Weichhaus Michael
Published: September 2024

Around 13% of women will likely develop breast cancer during their lifetime. Advances in cancer metabolism research have identified a range of metabolic reprogramming events, such as altered glucose and amino acid uptake, increased reliance on glycolysis, and interactions with the tumor microenvironment (TME), all of which present new opportunities for targeted therapies. However, studying these metabolic networks is challenging in traditional 2D cell cultures, which often fail to replicate the three-dimensional architecture and dynamic interactions of real tumors. To address this, organoid models have emerged as powerful tools. Tumor organoids are 3D cultures, often derived from patient tissue, that more accurately mimic the structural and functional properties of actual tumor tissues in vivo, offering a more realistic model for investigating cancer metabolism. This review explores the unique metabolic adaptations of breast cancer and discusses how organoid models can provide deeper insights into these processes. We evaluate the most advanced tools for studying cancer metabolism in three-dimensional culture models, including optical metabolic imaging (OMI), matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), and recent advances in conventional techniques applied to 3D cultures. Finally, we explore the progress made in identifying and targeting potential therapeutic targets in breast cancer metabolism.