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16 pages, 3432 KB  
Article
Genetic Architecture and Meta-QTL Identification of Yield Traits in Maize (Zea mays L.)
by Xin Li, Xiaoqiang Zhao, Siqi Sun, Meiyue He, Jing Wang, Xinxin Xiang and Yining Niu
Plants 2025, 14(19), 3067; https://doi.org/10.3390/plants14193067 (registering DOI) - 4 Oct 2025
Abstract
Yield components are the most important breeding objectives, directly determining maize high-yield breeding. It is well known that these traits are controlled by a large number of quantitative trait loci (QTL). Therefore, deeply understanding the genetic basis of yield components and identifying key [...] Read more.
Yield components are the most important breeding objectives, directly determining maize high-yield breeding. It is well known that these traits are controlled by a large number of quantitative trait loci (QTL). Therefore, deeply understanding the genetic basis of yield components and identifying key regulatory candidate genes can lay the foundation for maize marker-assisted selection (MAS) breeding. In this study, our aim was to identify the key genomic regions that regulate maize yield component formation through bioinformatic methods. Herein, 554 original QTLs related to 11 yield components, including ear length (EL), hundred-kernel weight (HKW), ear weight (EW), cob weight (CW), ear diameter (ED), cob diameter (CD), kernel row number (KRN), kernel number per row (KNR), kernel length (KL), grain weight per plant (GW), and kernel width (KW) in maize, were collected from the MaizeGDB, national center for biotechnology information (NCBI), and China national knowledge infrastructure (CNKI) databases. The consensus map was then constructed with a total length of 7154.30 cM. Approximately 80.32% of original QTLs were successfully projected on the consensus map, and they were unevenly distributed on the 10 chromosomes (Chr.). Moreover, 44 meta-QTLs (MQTLs) were identified by the meta-analysis. Among them, 39 MQTLs controlled two or more yield components, except for the MQTL4 in Chr. 1, which was associated with HKW; MQTL11 in Chr. 2, which was responsible for EL; MQTL19 in Chr. 3, which was related to KRN; MQTL26 in Chr. 5, which was involved in HKW; and MQTL36 in Chr. 7, which regulated EL. These findings were consistent with the Pearson correlation results, indicating that these traits exhibited co-linked heredity phenomena. Meanwhile, 159 candidate genes were found in all of the above MQTLs intervals, of which, 29 genes encoded E3 ubiquitin protein ligase, which was related with kernel size and weight. Other genes were involved in multiple metabolic processes, including plant hormones signaling transduction, plant growth and development, sucrose–starch synthesis and metabolism, and reproductive growth. Overall, the results will provide reliable genetic resources for high-yield molecular breeding in maize. Full article
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35 pages, 8491 KB  
Article
Pathogen Survey in Agrocybe chaxingu and Characterization of the Dominant Pathogen Fuligo gyrosa
by Xutao Chen, Guoliang Meng, Mengqian Liu, Jiancheng Dai, Guanghua Huo, Caihong Dong and Yunhui Wei
Horticulturae 2025, 11(10), 1190; https://doi.org/10.3390/horticulturae11101190 - 2 Oct 2025
Abstract
Agrocybe chaxingu is a commercially important edible mushroom in China, valued for its rich bioactive compounds and distinctive umami flavor. In recent years, frequent disease outbreaks have severely limited production, as many pathogens spread rapidly and are difficult to control, posing a significant [...] Read more.
Agrocybe chaxingu is a commercially important edible mushroom in China, valued for its rich bioactive compounds and distinctive umami flavor. In recent years, frequent disease outbreaks have severely limited production, as many pathogens spread rapidly and are difficult to control, posing a significant threat to the sustainable development of the industry. In this study, a systematic disease survey across major A. chaxingu cultivation areas in Jiangxi Province led to the isolation and identification of 17 potential fungal pathogens and 2 potential myxomycete pathogens using combined morphological characterization and multilocus phylogenetic analyses including the internal transcribed spacer (ITS) region, 28S large subunit ribosomal RNA (LSU), translation elongation factor (tef1), RNA polymerase largest subunit (rpb1), RNA polymerase second largest subunit (rpb2), Histone (H3), Beta tubulin (tub2), and 18S ribosomal RNA (18S rRNA). Among the identified diseases, white slime disease showed the highest incidence (17.3%) and was attributed to the slime mold Fuligo gyrosa, with pathogenicity confirmed according to Koch’s postulates. F. gyrosa proved highly virulent to both fruiting bodies and mycelia, enveloping host mycelium via plasmodial expansion, inhibiting growth, inducing structural rupture, and causing progressive degradation. Infection was accompanied by the deposition of characteristic stress-related pigments in the mycelium. This study provides the first detailed characterization of F. gyrosa infection dynamics in A. chaxingu mycelium. These findings provide new insights into the myxomycete pathogenesis in edible fungi and provide a foundation for the accurate diagnosis, targeted prevention, and sustainable management of diseases in A. chaxingu cultivation. Full article
(This article belongs to the Special Issue Advances in Propagation and Cultivation of Mushroom)
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16 pages, 648 KB  
Review
Clean to Prevent, Monitor to Protect: A Scoping Review on Strategies for Monitoring Cleaning in Hospitals to Prevent HAIs
by Biagio Santella, Antonio Donato, Luigi Fortino, Vittoria Satriani, Rosaria Flora Ferrara, Emanuela Santoro, Walter Longanella, Gianluigi Franci, Mario Capunzo and Giovanni Boccia
Infect. Dis. Rep. 2025, 17(5), 120; https://doi.org/10.3390/idr17050120 - 21 Sep 2025
Viewed by 272
Abstract
Background/Objectives: Hospital environmental contamination represents a significant source of healthcare-associated infections, yet standardized monitoring approaches are still inconsistent globally. This scoping review aimed to find and assess various tools and strategies used to monitor hospital environmental cleaning and disinfection practices, mapping current evidence [...] Read more.
Background/Objectives: Hospital environmental contamination represents a significant source of healthcare-associated infections, yet standardized monitoring approaches are still inconsistent globally. This scoping review aimed to find and assess various tools and strategies used to monitor hospital environmental cleaning and disinfection practices, mapping current evidence and finding research gaps to inform evidence-based recommendations for healthcare facilities. Methods: Following PRISMA Scoping Review guidelines, we conducted comprehensive searches on PubMed and Scopus databases from 2010–2025 using terms related to environmental monitoring, surface sampling, air sampling, and infection control in hospital settings. Eighteen studies met inclusion criteria; data were extracted using standardized forms and synthesized narratively, organizing findings by monitoring approach categories. Results: These studies revealed diverse monitoring approaches including fluorescent markers (22.2%), ATP bioluminescence assays (33.3%), microbiological methods (44.4%), and direct observation techniques (27.8%). MRSA was the most frequently targeted pathogen (55.6%), with limited attention to Gram-negative multidrug-resistant organisms and fungi. Studies showed significant variability in pass/fail thresholds (ATP: 50–500 RLU) and lack of standardized benchmarks. Recent research (50% post-2021) increasingly incorporates molecular techniques and digital technologies, though implementation remains resource intensive. Conclusions: A multimodal approach combining visual inspection, ATP assays, and microbiological methods appears most effective for comprehensive environmental monitoring. Critical gaps include lack of standardized thresholds, limited pathogen diversity focus, and insufficient integration of emerging digital technologies. Future research should focus on setting universal standards, expanding pathogen coverage, and assessing cost-effective monitoring strategies, all while ensuring legal compliance with hygiene regulations to enhance patient safety. Full article
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26 pages, 2824 KB  
Review
The Mechanisms of Resistance to JAK Inhibitors in Lymphoid Leukemias: A Scoping Review of Evidence from Preclinical Models and Case Reports
by Daniel Martínez Anaya, Marian Valladares Coyotecatl, Maria del Pilar Navarrete Meneses, Sergio Enríquez Flores and Patricia Pérez-Vera
Int. J. Mol. Sci. 2025, 26(18), 9111; https://doi.org/10.3390/ijms26189111 - 18 Sep 2025
Viewed by 177
Abstract
The use of JAK inhibitors (JAKi) represents a promising therapeutic approach for patients with lymphoid leukemias (Lym-L). Clinical trials are ongoing to evaluate the safety and efficacy of JAK inhibitors. Over the last years, there have been reports of preclinical Lym-L models that [...] Read more.
The use of JAK inhibitors (JAKi) represents a promising therapeutic approach for patients with lymphoid leukemias (Lym-L). Clinical trials are ongoing to evaluate the safety and efficacy of JAK inhibitors. Over the last years, there have been reports of preclinical Lym-L models that developed JAKi resistance, and reports of patients treated with JAKi who experienced treatment failure. Although evidence shows that there are diverse JAKi mechanisms, no review studies have been performed that summarize and discuss this information. This scoping review aimed to provide an updated overview of the mechanisms underlying JAKi molecular resistance in Lym-L. According to a scoping review PRISMA guidelines, a search was conducted in the PubMed and Europe PMC databases for studies published from 2010 to 2024. We included articles that described the molecular resistance to JAKi in Lym-L preclinical models or patients. The search was complemented by a review of laboratory-engineered resistant mutations in genomic datasets to obtain more information about their presence in patients with Lym-L. Twenty-two articles were eligible for this review, and six different mechanisms of molecular resistance were identified: (1) point mutations in the kinase domain, (2) cooperation between double-JAK mutants, (3) inactivation of phosphatases, (4) evasion of JAK inhibition due to trans-phosphorylation of JAK family proteins, (5) upregulation of pro-survival proteins, and (6) activation of kinase cross-signaling pathways. The integrated evidence enabled the identification of specific mechanisms of molecular resistance to JAKi in Lym-L, as well as promising therapeutic approaches to prevent them. These include selecting a sensitive JAKi, choosing an effective dosage regimen, and combining inhibitory molecules. Full article
(This article belongs to the Special Issue Advances in Molecular Target and Anti-Cancer Therapies)
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15 pages, 562 KB  
Article
The Effect of a Four-Month Low-Carbohydrate Diet on Visceral Adipose Tissue in Obese Subjects with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
by Ornella Rotolo, Caterina Bonfiglio, Rosa Reddavide, Anna Maria Cisternino, Rosa Inguaggiato and Gianluigi Giannelli
Nutrients 2025, 17(17), 2905; https://doi.org/10.3390/nu17172905 - 8 Sep 2025
Viewed by 691
Abstract
Background: Previous studies have shown a relationship between Visceral Adipose Tissue (VAT) and Hepatic Fat Content (HFC), and increases in HFC are linked to metabolic abnormalities similar to those associated with elevated VAT. Several short-term and long-term studies have supported these findings. Lifestyle [...] Read more.
Background: Previous studies have shown a relationship between Visceral Adipose Tissue (VAT) and Hepatic Fat Content (HFC), and increases in HFC are linked to metabolic abnormalities similar to those associated with elevated VAT. Several short-term and long-term studies have supported these findings. Lifestyle interventions remain the cornerstone of treatment for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), although the ideal dietary regimen is still under debate. Methods: Data on 2040 patients were extracted from the Clinical Nutrition Unit database between 2017 and 2019. Of these, 474 subjects with MASLD and Body Mass Index (BMI) ≥ 35 kg/m2 were treated with a four-month low-carbohydrate dietary intervention called the “Strong Diet” (StD). VAT and liver stiffness were measured at baseline and after four months of treatment using ultrasound. Results: Our study demonstrates the significant efficacy of StD in reducing VAT in MASLD patients with moderate hepatic steatosis. In subjects with severe steatosis, there is no statistically significant response to dietary intervention. This may be attributed to several irreversible molecular mechanisms that fundamentally alter the hepatic microenvironment and limit the liver’s capacity for regeneration and metabolic recovery. Conclusions: Improvements were largely confined to patients with moderate MASLD, with limited benefit in severe disease. Although dietary intervention remains the cornerstone of MASLD management, patients with severe steatosis should be informed about the potential limited resolution of steatosis, even with optimal metabolic control. Full article
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17 pages, 1171 KB  
Review
Applications and Challenges of Modern Analytical Techniques for the Identification of Plant Gum in the Polychrome Cultural Heritage
by Liang Xu, Weijia Zhu, Xi Chen and Xinyou Liu
Coatings 2025, 15(9), 1042; https://doi.org/10.3390/coatings15091042 - 5 Sep 2025
Viewed by 357
Abstract
Plant gums have long served as essential binding media in polychrome cultural heritage, contributing to pigment adhesion, surface cohesion, and long-term stability. This review evaluates recent advances in analytical technologies, including FTIR, Raman spectroscopy, GC-MS, LC-MS/MS, MALDI-TOF MS, hyperspectral imaging, and immunological assays, [...] Read more.
Plant gums have long served as essential binding media in polychrome cultural heritage, contributing to pigment adhesion, surface cohesion, and long-term stability. This review evaluates recent advances in analytical technologies, including FTIR, Raman spectroscopy, GC-MS, LC-MS/MS, MALDI-TOF MS, hyperspectral imaging, and immunological assays, for the identification of gums such as gum arabic, peach gum, and tragacanth in diverse cultural contexts. Drawing on case studies from 19th-century watercolours, ancient Egyptian coffins, and Maya murals, the paper demonstrates how these methods enable precise chemical characterization even in complex, aged, and mineral-rich matrices. Such information directly aids conservators in selecting compatible restoration materials, tailoring treatment protocols, and assessing deterioration mechanisms. Persistent challenges remain, including gum degradation, spectral interference from pigments and restoration materials, sample heterogeneity, and limited reference libraries, particularly for non-European species. Future research directions emphasize multi-modal, non-invasive workflows that integrate hyperspectral imaging with spectroscopic and chromatographic methods, drone-assisted micro-Raman for inaccessible surfaces, machine learning-assisted spectral databases, and bio-inspired adhesives replicating historical rheology. By linking molecular identification to conservation decision-making, plant gum analysis not only deepens our understanding of historical material practices but also strengthens the scientific basis for sustainable heritage preservation strategies. Full article
(This article belongs to the Section Surface Characterization, Deposition and Modification)
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14 pages, 1200 KB  
Article
Mutational Characterization of Astrocytoma, IDH-Mutant, CNS WHO Grade III in the AACR GENIE Database
by Elijah Torbenson, Beau Hsia, Nigel Lang and Peter Silberstein
DNA 2025, 5(3), 43; https://doi.org/10.3390/dna5030043 - 4 Sep 2025
Viewed by 536
Abstract
Background/Objectives: Astrocytoma, IDH-mutant, CNS WHO grade 3, is a diffuse glioma with poor prognosis, molecularly defined by IDH mutations and frequently co-occurring TP53 and ATRX alterations. This study aimed to delineate the genomic landscape and identify clinically relevant molecular features of astrocytoma, IDH-mutant, [...] Read more.
Background/Objectives: Astrocytoma, IDH-mutant, CNS WHO grade 3, is a diffuse glioma with poor prognosis, molecularly defined by IDH mutations and frequently co-occurring TP53 and ATRX alterations. This study aimed to delineate the genomic landscape and identify clinically relevant molecular features of astrocytoma, IDH-mutant, CNS WHO grade 3 using this resource. Methods: Patients in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (AACR Project GENIE) database were selected based on histological diagnosis of “anaplastic astrocytoma”, confirmed IDH1/2 mutation, and exclusion of CDKN2A/B homozygous deletions. We analyzed frequencies of somatic mutations, copy number alterations (CNAs), structural variants (SVs), assessed co-occurrence/exclusivity patterns, and explored associations with available demographic and limited survival data. Results: The most common somatic mutations were in IDH1 (98.0%), TP53 (94.8%), and ATRX (55.2%). The observed ATRX mutation frequency was lower than some historical reports (e.g., ~86%). Other recurrent alterations included phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (6.9%), Notch receptor 1 (NOTCH1) (6.9%), and platelet-derived growth factor receptor alpha (PDGFRA) (mutations 4.3%; CNAs also observed). Conclusions: This study provides a comprehensive genomic characterization of astrocytoma, IDH-mutant, CNS WHO grade 3 using the AACR GENIE database, confirming core mutational signatures while also highlighting potential variations in alteration frequencies, such as for ATRX. The findings establish a valuable real-world genomic benchmark for this tumor type, while promoting the need for continued data integration with robust clinical outcomes to identify actionable prognostic and therapeutic targets. Full article
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18 pages, 1842 KB  
Review
The Impact of HIV Infection and Aging on Periodontitis
by Sophia DeVore, Dalia Seleem and Miou Zhou
Oral 2025, 5(3), 64; https://doi.org/10.3390/oral5030064 - 1 Sep 2025
Viewed by 575
Abstract
Background: Periodontal disease is a common chronic inflammatory disease affecting the oral cavity involving the tissues supporting teeth. It is a significant oral health concern worldwide, particularly amongst individuals living with human immunodeficiency virus (HIV). Biological aging is associated with a natural decline [...] Read more.
Background: Periodontal disease is a common chronic inflammatory disease affecting the oral cavity involving the tissues supporting teeth. It is a significant oral health concern worldwide, particularly amongst individuals living with human immunodeficiency virus (HIV). Biological aging is associated with a natural decline in the immune system, which can also affect the severity of periodontitis and other potential risk factors. In people living with HIV (PLWH), the contribution of both the HIV infection and the aging process can lead to increased susceptibility to periodontal disease. Objectives: This paper aims to review the recent literature about the relationships between HIV infection and early aging and their impact on periodontitis, and to inform interested clinicians about the current literature on the intersection between and within these topics. Methods: This review explores the recent literature on the complex relationship between HIV, aging, and periodontitis. The PubMed, ScienceDirect, and Medline databases were used to find clinical research studies within the last 10 years to identify significant correlations between HIV, aging, and periodontitis. Results: These studies identify key pathogens, molecules, or cellular pathways that contribute to a more comprehensive understanding of the pathophysiologic processes that link HIV, aging, and periodontitis. This complex relationship is multifactorial, involving immune dysfunction, microbial dysbiosis, and inflammatory pathways that still need further research. Conclusions: Overall, this exploration through molecular and cellular mechanisms underlying the relationships between aging, HIV, and periodontitis can provide therapeutic implications for dental clinicians to prevent and treat their affected patients. Full article
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38 pages, 867 KB  
Review
Medicinal Plants for Child Mental Health: Clinical Insights, Active Compounds, and Perspectives for Rational Use
by Giovanna Rigillo, Joan M. C. Blom, Arianna Cocchi, Valentina Martinucci, Francesca Favaro, Giulia Baini, Giorgio Cappellucci, Fabio Tascedda and Marco Biagi
Children 2025, 12(9), 1142; https://doi.org/10.3390/children12091142 - 28 Aug 2025
Viewed by 1148
Abstract
Background/Objectives: Anxiety, agitation, and mood disturbances are increasingly common among children and adolescents. Given the limitations of conventional pharmacological treatments in the pediatric population, particularly for subthreshold or mild conditions, interest in complementary approaches such as phytotherapy is growing. This review aims to [...] Read more.
Background/Objectives: Anxiety, agitation, and mood disturbances are increasingly common among children and adolescents. Given the limitations of conventional pharmacological treatments in the pediatric population, particularly for subthreshold or mild conditions, interest in complementary approaches such as phytotherapy is growing. This review aims to critically evaluate the clinical evidence supporting the use of herbal medicines and botanical food supplements for mental health symptoms in youths and to explore the pharmacological basis of their activity. Methods: A systematic search was conducted across main databases for clinical trials involving herbal products for psychologically related symptoms in children and adolescents. Eligible studies included those using registered herbal medicines, as well as authorized food supplements, that evaluated behavioral or cognitive outcomes. In addition, bioinformatic analyses were performed on selected phytocompounds to predict their molecular targets. Results: Twenty-nine clinical trials were identified, including eighteen targeting pathological conditions (notably attention deficit/hyperactivity disorder (ADHD), anxiety, and depression) and eleven addressing borderline symptoms such as nervous agitation, restlessness, or sleep disturbances. Herbal products showing clinical promise include Bacopa monnieri (L.) Wettst., Crocus sativus L., Ginkgo biloba L., Hypericum perforatum L., Lavandula angustifolia Mill., Melissa officinalis L., Panax ginseng C.A. Meyer, Passiflora incarnata L., Pinus pinaster Aiton, Valeriana officinalis L., and Withania somnifera (L.) Dunal. Bioinformatic predictions revealed polypharmacological activity profiles involving neuroinflammatory, neuroprotective, and neurotransmitter-related pathways. Conclusions: This review highlights both the potential and the current limitations of herbal products in pediatric mental health care. Evidence supports their use for selected indications, provided that standardized preparations and clinical oversight are ensured. Further research is essential, particularly to inform dosing, safety, and integrative care strategies. Full article
(This article belongs to the Special Issue Advances in Mental Health and Well-Being in Children (2nd Edition))
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16 pages, 1181 KB  
Article
Histone-, Receptor-, and Integrin-Related Gene Products and ADAM28 as Relevant to B-Cell Acute Lymphoblastic Leukemia (B-ALL)
by Makayla R. K. Wilkins and Brett E. Pickett
Curr. Issues Mol. Biol. 2025, 47(9), 699; https://doi.org/10.3390/cimb47090699 - 28 Aug 2025
Viewed by 474
Abstract
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with pediatric ALL having a ~90 percent cure rate, while the adult cure rate is considerably lower. B-cell acute lymphoblastic leukemia (B-ALL) is the most common subtype of ALL and is generally treated [...] Read more.
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with pediatric ALL having a ~90 percent cure rate, while the adult cure rate is considerably lower. B-cell acute lymphoblastic leukemia (B-ALL) is the most common subtype of ALL and is generally treated through a variety of chemotherapy drugs that can cause undesired side effects, adverse events, or other complications. Consequently, there is a need for improved understanding of the shared gene expression profiles and underlying molecular mechanisms shared among various B-ALL subtypes. In this study, 259 publicly available RNA-sequencing samples were evaluated and retrieved from the NCBI Gene Expression Omnibus (GEO) database and then pre-processed using a robust computational workflow. Differential gene expression, pathway enrichment, marker prediction, and drug repurposing analyses were then performed to facilitate a better mechanistic understanding of disease. We found both previously identified as well as novel differentially expressed genes. Specifically, we observed upregulation in the HIST2H2AA3, EPHA7, and MPR1 genes; while downregulation was observed for the IGHA1, ANGPTL1, and CHAD genes. We identified multiple pathways, including “Integrins in Angiogenesis”, to be significantly affected in B-ALL. We then used these significant pathways to predict and rank 306 existing therapeutic targets that could potentially be repurposed for B-ALL, including three that have not been evaluated in human clinical trials. Using a tree-based classification algorithm, we also predicted ADAM28 as a possible mechanistic marker. The results of this study have potential implications for patients who have been diagnosed with B-ALL by providing improved mechanistic understanding and information on possible diagnostics and repurposed therapeutics for B-ALL. Full article
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17 pages, 1414 KB  
Review
Precision Medicine in Orthobiologics: A Paradigm Shift in Regenerative Therapies
by Annu Navani, Madhan Jeyaraman, Naveen Jeyaraman, Swaminathan Ramasubramanian, Arulkumar Nallakumarasamy, Gabriel Azzini and José Fábio Lana
Bioengineering 2025, 12(9), 908; https://doi.org/10.3390/bioengineering12090908 - 24 Aug 2025
Viewed by 1155
Abstract
The evolving paradigm of precision medicine is redefining the landscape of orthobiologic therapies by moving beyond traditional diagnosis-driven approaches toward biologically tailored interventions. This review synthesizes current evidence supporting precision orthobiologics, emphasizing the significance of individualized treatment strategies in musculoskeletal regenerative medicine. This [...] Read more.
The evolving paradigm of precision medicine is redefining the landscape of orthobiologic therapies by moving beyond traditional diagnosis-driven approaches toward biologically tailored interventions. This review synthesizes current evidence supporting precision orthobiologics, emphasizing the significance of individualized treatment strategies in musculoskeletal regenerative medicine. This narrative review synthesized literature from PubMed, Embase, and Web of Science databases (January 2015–December 2024) using search terms, including ‘precision medicine,’ ‘orthobiologics,’ ‘regenerative medicine,’ ‘biomarkers,’ and ‘artificial intelligence’. Biological heterogeneity among patients with ostensibly similar clinical diagnoses—reflected in diverse inflammatory states, genetic backgrounds, and tissue degeneration patterns—necessitates patient stratification informed by molecular, genetic, and multi-omics biomarkers. These biomarkers not only enhance diagnostic accuracy but also improve prognostication and monitoring of therapeutic responses. Advanced imaging modalities such as T2 mapping, DTI, DCE-MRI, and molecular PET offer non-invasive quantification of tissue health and regenerative dynamics, further refining patient selection and treatment evaluation. Simultaneously, bioengineered delivery systems, including hydrogels, nanoparticles, and scaffolds, enable precise and sustained release of orthobiologic agents, optimizing therapeutic efficacy. Artificial intelligence and machine learning approaches are increasingly employed to integrate high-dimensional clinical, imaging, and omics datasets, facilitating predictive modeling and personalized treatment planning. Despite these advances, significant challenges persist—ranging from assay variability and lack of standardization to regulatory and economic barriers. Future progress requires large-scale multicenter validation studies, harmonization of protocols, and cross-disciplinary collaboration. By addressing these limitations, precision orthobiologics has the potential to deliver safer, more effective, and individualized care. This shift from generalized to patient-specific interventions holds promise for improving outcomes in degenerative and traumatic musculoskeletal disorders through a truly integrative, data-informed therapeutic framework. Full article
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23 pages, 2805 KB  
Article
Systematic Analysis of Alternative Splicing in Transcriptomes of Multiple Sclerosis Patient Brain Samples
by Müge Sak, Julia H. Chariker and Eric C. Rouchka
Int. J. Mol. Sci. 2025, 26(17), 8195; https://doi.org/10.3390/ijms26178195 - 23 Aug 2025
Viewed by 746
Abstract
Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease affecting approximately 1 million people in the United States. Despite extensive research into the mechanisms of disease development, many aspects of the biological changes during MS progression and the varying symptoms among patients remain [...] Read more.
Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease affecting approximately 1 million people in the United States. Despite extensive research into the mechanisms of disease development, many aspects of the biological changes during MS progression and the varying symptoms among patients remain unclear. In the era of high-throughput sequencing, transcriptome databases are flooded with data. However, bulk RNA sequencing (RNA-seq) data are typically used only for differential gene expression analysis. Alternative splicing, a key process that alters the transcriptome, can also be identified from bulk data. Here, we accessed 11 studies with bulk RNA-seq data of postmortem MS patients’ brain samples via NCBI’s Gene Expression Omnibus (GEO). We extracted additional information from these data by identifying exclusively alternatively spliced genes via replicate multivariate analysis of transcript splicing (rMATS) analysis. Our analyses revealed that changes in RNA splicing mediate distinct biological signals compared to those driven by differential gene expression. Gene ontology and protein do-main analyses of genes exclusively regulated by alternative splicing revealed distinct molecular differences between progressive and relapsing–remitting MS as well as among lesions from different brain regions and between white and gray matter. These findings highlight the critical role of alternative splicing and its associated pathways in MS disease development and progression. Full article
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14 pages, 2452 KB  
Article
Genome Survey Sequencing of Indigofera pseudotinctoria and Identification of Its SSR Markers
by Jing Chen, Qifan Ran, Yuandong Xu, Junming Zhao, Xiao Ma, Wei He and Yan Fan
Genes 2025, 16(9), 991; https://doi.org/10.3390/genes16090991 - 23 Aug 2025
Viewed by 443
Abstract
Background: Indigofera pseudotinctoria, a traditional Chinese forage and medicine widely used in East Asia, holds significant economic and agricultural value. Despite this, genomic information regarding I. pseudotinctoria remains conspicuously lacking. Methods: In this study, we utilized genome survey sequencing to elucidate the [...] Read more.
Background: Indigofera pseudotinctoria, a traditional Chinese forage and medicine widely used in East Asia, holds significant economic and agricultural value. Despite this, genomic information regarding I. pseudotinctoria remains conspicuously lacking. Methods: In this study, we utilized genome survey sequencing to elucidate the complete genome sequence of this species. Results: The genome size of I. pseudotinctoria to be around 637–920 Mb with a heterozygosity rate of 0.98% and a repeat rate of 66.3%. A total of 240,659 simple sequence repeat (SSR) markers were predicted in the genome of I. pseudotinctoria. Substantial differences were observed among nucleotide repeat types, for instance, mononucleotide repeats were found to be predominant (62.47%), whereas pentanucleotide repeats were notably scarce (0.24%). Furthermore, among dinucleotide and trinucleotide repeats, sequence motifs AT/AT (66.57%) and AAT/ATT (54.15%) were found to be particularly abundant. Among the identified unigenes, 58,790 exhibited alignment with known genes in established databases, including 33,218 genes within the Gene Ontology (GO) database and 10,893 genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Conclusions: This study marks the first attempt to both sequence and delineate the genomic landscape of I. pseudotinctoria. Importantly, it will serve as a foundational reference for subsequent comprehensive genome-wide deep sequencing and the development of SSR molecular markers within the scope of I. pseudotinctoria research. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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44 pages, 3081 KB  
Review
From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer’s Disease Landscape
by Anastasia Bougea, Manuel Debasa-Mouce, Shelly Gulkarov, Mónica Castro-Mosquera, Allison B. Reiss and Alberto Ouro
Medicina 2025, 61(8), 1462; https://doi.org/10.3390/medicina61081462 - 14 Aug 2025
Cited by 1 | Viewed by 1962
Abstract
Background and Objectives: Over the past few years, there has been a significant shift in focus from developing better diagnostic tools to detecting Alzheimer’s disease (AD) earlier and initiating treatment interventions. This review will explore four main objectives: (a) the role of [...] Read more.
Background and Objectives: Over the past few years, there has been a significant shift in focus from developing better diagnostic tools to detecting Alzheimer’s disease (AD) earlier and initiating treatment interventions. This review will explore four main objectives: (a) the role of biomarkers in enhancing the diagnostic accuracy of AD, highlighting the major strides that have been made in recent years; (b) the role of neuropsychological testing in identifying biomarkers of AD, including the relationship between cognitive performance and neuroimaging biomarkers; (c) the amyloid hypothesis and possible molecular mechanisms of AD; and (d) the innovative AD therapeutics and the challenges and limitations of AD research. Materials and Methods: We have searched PubMed and Scopus databases for peer-reviewed research articles published in English (preclinical and clinical studies as well as relevant reviews and meta-analyses) investigating the molecular mechanisms, biomarkers, and treatments of AD. Results: Genome-wide association studies (GWASs) discovered 37 loci associated with AD risk. Core 1 biomarkers (α-amyloid Aβ42, phosphorylated tau, and amyloid PET) detect early AD phases, identifying both symptomatic and asymptomatic individuals, while core 2 biomarkers inform the short-term progression risk in individuals without symptoms. The recurrent failures of Aβ-targeted clinical studies undermine the amyloid cascade hypothesis and the objectives of AD medication development. The molecular mechanisms of AD include the accumulation of amyloid plaques and tau protein, vascular dysfunction, neuroinflammation, oxidative stress, and lipid metabolism dysregulation. Significant advancements in drug delivery technologies, such as focused Low-Ultrasound Stem, T cells, exosomes, nanoparticles, transferin, nicotinic and acetylcholine receptors, and glutathione transporters, are aimed at overcoming the BBB to enhance treatment efficacy for AD. Aducanumab and Lecanemab are IgG1 monoclonal antibodies that retard the progression of AD. BACE inhibitors have been explored as a therapeutic strategy for AD. Gene therapies targeting APOE using the CRISPR/Cas9 genome-editing system are another therapeutic avenue. Conclusions: Classic neurodegenerative biomarkers have emerged as powerful tools for enhancing the diagnostic accuracy of AD. Despite the supporting evidence, the amyloid hypothesis has several unresolved issues. Novel monoclonal antibodies may halt the AD course. Advances in delivery systems across the BBB are promising for the efficacy of AD treatments. Full article
(This article belongs to the Section Neurology)
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20 pages, 1995 KB  
Systematic Review
MALDI-TOF MS Biomarkers for Methicillin-Resistant Staphylococcus aureus Detection: A Systematic Review
by Pedro Santos, Irina Alho and Edna Ribeiro
Metabolites 2025, 15(8), 540; https://doi.org/10.3390/metabo15080540 - 8 Aug 2025
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Abstract
Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) infections remain a significant challenge in healthcare. Conventional and molecular techniques used for MRSA identification are either time-consuming or costly. Alternatively, Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) offers a rapid method for microbial identification and has [...] Read more.
Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) infections remain a significant challenge in healthcare. Conventional and molecular techniques used for MRSA identification are either time-consuming or costly. Alternatively, Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) offers a rapid method for microbial identification and has the potential to detect biomarkers that distinguish methicillin resistance in S. aureus isolates. The aim of this study was to identify methicillin-resistant discriminative biomarkers for S. aureus obtained using MALDI-TOF MS. Methods: A systematic review was conducted by searching databases such as PubMed and Web of Science for studies that focused on MRSA detection with biomarkers by MALDI-TOF MS, including all relevant studies published up to July 2024. The review protocol was registered in PROSPERO registry. Results: A total of 15 studies were selected for analysis. Data were extracted on study location, sample size, MALDI-TOF MS analyzer, sample preparation, methicillin resistance and sensitivity biomarkers, and the use of Artificial Intelligence (AI) models. Notably, PSM-mec and delta toxin were frequently reported as informative biomarkers, detectable at 2414 ± 2 Da and 3006 ± 2 Da, respectively. Additionally, eight studies used AI models to identify specific biomarkers differentiating methicillin-resistant and methicillin-sensitive strains, based on differences in peak intensities or the exclusive presence of certain peaks. Moreover, two studies employed detection of MRSA in low concentrations from biological samples and others employed an optimized matrix solution for improved analysis. Conclusions: Overall, MALDI-TOF MS is not only a powerful tool for the identification of bacterial isolates but also shows strong potential for rapid, cost-effective detection of methicillin resistance in S. aureus through biomarker analysis. Given that it is already implemented in several clinical laboratories, this approach could be adopted without significant additional cost. Full article
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