Search Results (8,260)

This paper presents a hybrid pipeline based on zero-shot vision models for automatic node count estimation in Lisianthus (Eustoma grandiflorum) cultivation and a system for real-time growth information sharing. The multistage image analysis pipeline integrates Grounding DINO for zero-shot leaf-region detection, MiDaS for monocular depth estimation, and a YOLO-based classifier, using daily time-lapse images from low-cost fixed cameras in commercial greenhouses. The model parameters are derived from field measurements of 2024 seasonal crops (Trial 1) and then applied to different cropping seasons, growers, and cultivars (Trials 2 and 3) without any additional retraining. Trial 1 indicates high accuracy (R² = 0.930, mean absolute error (MAE) = 0.73). Generalization performance is confirmed in Trials 2 (MAE = 0.45) and 3 (MAE = 1.14); reproducibility across multiple growers and four cultivars yields MAEs of approximately ±1 node. The model effectively captures the growth progression despite variations in lighting, plant architecture, and grower practices, although errors increase during early growth stages and under unstable leaf detection. Furthermore, an automated Discord-based notification system enables real-time sharing of node trends and analytical images, facilitating communication. The feasibility of combining zero-shot vision models with cloud-based communication tools for sustainable and collaborative floricultural production is thus demonstrated. Full article

Non-AIDS-defining cancers (NADCs) have emerged as an increasingly prominent cause of non-AIDS-related morbidity and mortality among people living with HIV (PLWH). However, the scarcity of NADC clinical samples, compounded by privacy and security constraints, continues to present formidable obstacles to advancing pathological and clinical investigations. In this study, we adopted a joint analysis strategy and deeply integrated and analyzed transcriptomic data from 12,486 PLWH and cancer patients to systematically identify potential key regulators for 23 NADCs. This effort culminated in NADCdb—a database specifically engineered for NADC pathological exploration, structured around three mechanistic frameworks rooted in the interplay of immunosuppression, chronic inflammation, carcinogenic viral infections, and HIV-derived oncogenic pathways. The “rNADC” module performed risk assessment by prioritizing genes with aberrant expression trajectories, deploying bidirectional stepwise regression coupled with logistic modeling to stratify the risks for 21 NADCs. The “dNADC” module, synergized patients’ dysregulated genes with their regulatory networks, using Random Forest (RF) and Conditional Inference Trees (CITs) to identify pathogenic drivers of NADCs, with an accuracy exceeding 75% (in the external validation cohort, the prediction accuracy of the HIV-associated clear cell renal cell carcinoma model exceeded 90%). Meanwhile, “iPredict” identified 1905 key immune biomarkers for 16 NADCs based on the distinct immune statuses of patients. Importantly, we conducted multi-dimensional profiling of these key determinants, including in-depth functional annotations, phenotype correlations, protein–protein interaction (PPI) networks, TF-miRNA-target regulatory networks, and drug prediction, to deeply dissect their mechanistic roles in NADC pathogenesis. In summary, NADCdb serves as a novel, centralized resource that integrates data and provides analytical frameworks, offering fresh perspectives and a valuable platform for the scientific exploration of NADCs. Full article

Chronic back pain (CBP) associated with intervertebral disc degeneration (IVDD) is a leading cause of medical consultations, decreased quality of life, and temporary and permanent disability. The mechanisms of CBP development and persistence in patients with IVDD have been studied for many years, but this issue remains far from resolved. The search for predictive biomarkers that could help identify patients with IVDD at high risk for CBP continues. In recent decades, research has shown increasing interest in identifying epigenetic biomarkers for this disorder. to summarize the results of preclinical and clinical studies on the role of microRNAs (miRs) as epigenetic biomarkers of the development and progression of CBP in patients with IVDD. English-language articles; original experimental (preclinical) studies; original clinical study; assessment of changes in systemic (in blood) and/or local (in intervertebral disk (IVD)) levels of miR expression in IVDD, either independently or in comparison with healthy controls; and studies that were completed and the results of which were published. PubMed, Springer, Google Scholar, Scopus, Oxford Press, Cochrane, and e-Library databases. Charting for this scoping review involved developing a data extraction form to summarize extracts and organize data from included studies. This was an iterative process where the charting tables and figures may be refined as the review progresses. 126 studies were analyzed in detail, focusing on their study designs and comparing changes in miR expression in animal models of IVDD and in patients with IVDD compared to healthy controls. During the preparation of this scoping review and upon subsequent detailed review of the original publications, it turned out that the results of one study were not justified by the authors due to identified technological problems (the article was withdrawn by the editorial board of the journal). Therefore, we excluded the results of this study from the subsequent analysis. As a result, this section summarizes the results of 60 preclinical and 65 clinical studies. Some miRs (e.g., miR-21 and miR-132) are associated with the regulation of inflammatory pathways that contribute to increased degradation of IVD extracellular matrix and enhanced nociceptive signaling through various mechanisms, contributing to the progression of CBP. Other miRs (e.g., miR-145 and miR-223) exert protective effects, enhance regenerative potential, and alleviate CBP. Despite the promising results of these studies, there are limitations in the use of miRs as perspective epigenetic biomarkers of CBP in patients with IVDD because the pattern of potentially predictive and protective miRs in relation to the mechanisms of CBP formation and progression in IVDD has not yet been sufficiently studied. The results of some preclinical and clinical studies are contradictory. Further research is needed to clarify the role of miR signatures in animal models and clinical trials on IVDD-specific CBP. Full article

Avobenzone (AVO) and ethylhexyl salicylate (EHS) are widely used organic UV filters with distinct photochemical properties and reported biological effects. Experimental and predictive evidence suggests that some lipophilic UV filters may reach systemic circulation and potentially cross the blood–brain barrier (BBB), raising concerns about possible central nervous system effects, although direct evidence for AVO and EHS remains limited. This study evaluated the effects of subcytotoxic concentrations (0.01–1 µM) of AVO and EHS on differentiated SH-SY5Y human neuroblastoma cells, focusing on early stress-related molecular responses. Cell viability and reactive oxygen species production were not significantly affected at any tested concentration. Integrated analyses of microRNA, gene, and protein expression revealed modest and variable modulation of miR-200a-3p and miR-29b-3p. Western blot analysis showed increased phosphorylation of AKT and ERK, no significant changes in mTOR activation, and an increased Bax/Bcl-2 ratio. Overall, these findings indicate that AVO and EHS trigger an early stress-adaptive response involving PI3K/AKT and MAPK/ERK signaling and modulation of apoptosis-related pathways. Such responses reflect a dynamic balance between cellular adaptation and pro-apoptotic signaling, which may become relevant under prolonged or higher-intensity exposure conditions. Full article

Prediabetes is accompanied by early β-cell stress and oxidative imbalance before overt hyperglycemia. Circulating extracellular vesicle (EV) microRNAs (miRNAs) may capture early metabolic disturbances, but their mechanistic relevance remains unclear. Plasma EV miRNA profiles were analyzed across normoglycemia, prediabetes, and newly diagnosed type 2 diabetes, with validation in an independent cohort (n = 150). Functional studies were performed in pancreatic β-cells exposed to glucolipotoxic stress to examine miRNA regulation, IFN-α signaling, mitochondrial redox status, and insulin secretion. Six EV miRNAs, including miR-186-5p, were consistently reduced in prediabetes and correlated with glycemic and insulin resistance indices. In β-cells, glucolipotoxic stress selectively suppressed miR-186-5p, leading to derepression of IFNA2, activation of IFN-α–JAK/STAT signaling, increased mitochondrial ROS, impaired ATP/ADP dynamics, and reduced glucose-stimulated insulin secretion. Restoration of miR-186-5p or pharmacologic JAK inhibition mitigated these defects, and luciferase assays confirmed IFNA2 as a direct target of miR-186-5p. EV-associated miR-186-5p represents an early marker of metabolic stress in prediabetes and provides mechanistic insight into IFN-α–driven oxidative and secretory dysfunction in β-cells. Full article

Background/Objectives: Peri-implantitis is a chronic inflammatory condition affecting tissues surrounding dental implants and is characterized by progressive marginal bone loss that can ultimately lead to implant failure. Reduced vascularization and impaired immune clearance in peri-implant tissues contribute to persistent inflammation and limited therapeutic efficacy. MicroRNAs (miRNAs), particularly miR-21, have emerged as key regulators of inflammatory responses and bone remodeling. The objective of this study was to develop a bioactive dental implant coating capable of locally delivering miR-21 to modulate inflammation and promote peri-implant tissue regeneration, thereby preventing peri-implantitis. Methods: Cationic nanoparticles were synthesized using lecithin and low-molecular-weight polyethylenimine (PEI) as a non-viral delivery system for miR-21. Lecithin was employed to enhance biocompatibility, while PEI functionalization provided a positive surface charge to improve miRNA complexation and cellular uptake. The resulting lecithin–PEI nanoparticles (LEC–PEI NPs) were incorporated into a chitosan-based coating and applied to titanium implant surfaces to obtain a sustained miR-21–releasing system (miR21-implant). Transfection efficiency and biological activity were evaluated in human periodontal ligament fibroblasts (hPDLFs) and compared with a commercial transfection reagent (Lipofectamine). Release kinetics and long-term activity of miR-21 from the coating were also assessed. Results: MiR-21-loaded LEC–PEI nanoparticles demonstrated significantly higher transfection efficiency than Lipofectamine and retained marked biological activity in hPDLFs relevant to peri-implantitis prevention. The chitosan-based nanoparticle coating enabled controlled and sustained miR-21 release over time, supporting prolonged modulation of inflammatory and osteogenic signaling pathways involved in peri-implant tissue homeostasis. Conclusions: The miR21-implant system, based on lecithin–PEI nanoparticles incorporated into a chitosan coating, represents a promising therapeutic strategy for peri-implantitis prevention. By enabling sustained local delivery of miR-21, this approach has the potential to preserve peri-implant bone architecture, modulate chronic inflammation, and enhance the osseointegration of titanium dental implants. Full article

Graves’ disease (GD) and Thyroid Eye Disease (TED) are autoimmune disorders characterized by significant heterogeneity in treatment response. Up to 50% of GD patients relapse after antithyroid drug (ATD) withdrawal, and a substantial portion of TED patients (20–50%) are resistant to first-line glucocorticoid (GC) therapy. This review evaluates the current evidence on epigenetic modifications as predictive biomarkers to guide personalized treatment. We synthesized recent findings (up to 2025) from PubMed, focusing on DNA methylation and microRNAs (miRNAs). For GD, ATD relapse risk is linked to a persistent “epigenetic memory” in T cells, notably the hypomethylation of Th17-associated genes. Circulating miRNA signatures, including miR-346, miR-23b-5p, and miR-92a-3p, also show promise in predicting remission. For TED, GC sensitivity is strongly correlated with specific circulating miRNAs. High pre-treatment levels of miR-146a predict a positive response (100% positive predictive value), while low levels of miR-224-5p predict non-responsiveness. While DNA methylation is confirmed in TED pathogenesis, its predictive role is unstudied. Major research gaps persist, particularly the near-total absence of data on histone modifications as predictive markers and the lack of epigenetic predictors for new biologics treatments, which currently rely on genetic or pharmacokinetic markers. Epigenetic biomarkers represent a promising frontier for stratifying patients and optimizing therapeutic strategies in Graves’ autoimmunity. Full article

Oncolytic coxsackievirus B3 (oCVB3) strain PD-H has shown potent oncolytic efficacy and a remarkable safety profile in the treatment of colorectal cancer in vivo after intratumoral (i.t.) injection. In this study, we investigated the safety and efficiency of PD-H following intravenous (i.v.) virus administration. When injected i.v. into Balb/C mice bearing subcutaneous Colon-26 tumors, PD-H led to slightly reduced tumor progression and a significant increase in animal survival, but it also caused multi-organ infection and tissue damage. To improve the safety profile of PD-H, we inserted microRNA target sites (miR-TS) of the heart-specific miR-1, pancreas-specific miR-375, liver-specific miR-122, and brain-specific miR-124 or the tumor-suppressor miR-145 into the genome of PD-H and generated the viruses PD-622TS and PD-145TS. Both viruses replicated similarly and induced cytotoxicity comparable to that of PD-H in the colorectal carcinoma cell lines Colon-26 and CT-26Luc. Their replication was inhibited in HEK293T cells transiently transfected with the cognate microRNAs. In vivo, i.v. administration of PD-145TS and PD-622TS to healthy Balb/C mouse resulted in significantly lower viral titers in the organs of mice and led to significantly less-intense pathological alterations compared to PD-H. PD-622TS injected i.v. into Balb/C mice with CT-26Luc-induced peritoneal carcinomatosis did not induce off-target alterations in normal organs, but it failed to induce a therapeutic effect. These data indicate that PD-H or microRNA-regulated PD derivatives exhibit only limited therapeutic efficacy following i.v. injection in colorectal tumor-bearing mice. However, the newly engineered microRNA-regulated PD-H variants demonstrate improved safety profiles. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype, with limited diagnostic options and no targeted early detection tools. Liquid biopsy represents a minimally invasive approach for detecting tumor-derived molecular alterations in body fluids. This scoping review aimed to comprehensively synthesize all liquid biopsy-derived molecular biomarkers evaluated for the diagnosis of TNBC in adults. Methods: This review followed the Arksey and O’Malley framework and PRISMA-ScR guidelines. Systematic searches of PubMed, Scopus, Embase, and Web of Science identified primary human studies evaluating circulating molecular biomarkers for TNBC diagnosis. Non-TNBC, non-human, hereditary, treatment-response, and nonmolecular studies were excluded. Data on study design, patient characteristics, biospecimen type, analytical platforms, biomarker class, and diagnostic performance were extracted and synthesized descriptively by biomolecule class. Results: Thirty-two studies met the inclusion criteria, comprising 15 protein-based, 12 RNA-based, and 6 DNA-based studies (one reporting both protein and RNA). In total, 1532 TNBC cases and 3137 participants in the comparator group were analyzed. Protein biomarkers were the most frequently studied, although only APOA4 appeared in more than one study, with conflicting results. RNA-based biomarkers identified promising candidates, particularly miR-21, but validation cohorts were scarce. DNA methylation markers showed promising diagnostic accuracy yet lacked replication. Most studies were small retrospective case–control designs with heterogeneous comparators and inconsistent diagnostic reporting. Conclusions: Evidence for liquid biopsy-derived biomarkers in TNBC remains limited, heterogeneous, and insufficiently validated. No biomarker currently shows reproducibility suitable for clinical implementation. Robust, prospective, and standardized studies are needed to advance liquid biopsy-based diagnostics in TNBC. Full article

MicroRNAs (miRNAs) are promising biomarkers for the early detection of various diseases, particularly cancer, driving active development of highly sensitive and selective detection technologies. This study aims to establish a novel miRNA detection technique that utilizes image analysis to track the Brownian motion (diffusivity) of fluorescent probe-modified miRNA particles. This method identifies the presence and concentration of miRNAs by exploiting the change in particle size upon hybridization with the target. Furthermore, the use of a probe modified with a photo-crosslinkable artificial nucleic acid (CNV-D) enables the covalent capture of the target miRNA, ensuring high selectivity in biological samples even under stringent washing conditions. By integrating Hybridization Chain Reaction (HCR), the complex size is significantly amplified, dramatically enhancing the detection sensitivity. Consequently, we successfully demonstrated the highly sensitive and specific detection of the cancer biomarker miR-21 in serum, achieving an exceptionally low limit of detection (LOD) of 1 fM. This technology holds great potential to contribute to the early diagnosis of cancer. Full article

Load balancing is a widely adopted strategy in modern distributed systems because it distributes workloads across servers, mitigating overload and improving overall performance. However, the rapid growth of such systems has created a need for more adaptive strategies to ensure optimal utilization and responsiveness of resources. Traditional algorithms such as Round Robin (RR) and Weighted Round Robin (WRR) assign requests without considering server states or request characteristics. We implement a machine learning (ML)–based predictive load balancer, forecasting the latency of a request based on the request itself and container parameters, specifically the average latency of the last 50 requests and the count of active requests, and evaluate it against RR and WRR. For the experiment, synthetic data were generated to replicate real-world requests by creating random URL and method combinations, attaching a task size in Million Instructions (MI), and distributing them among three containers with varying resources according to the load balancing strategies described above. Under the conditions tested, the ML approach achieved the worst performance, trailing both RR and WRR in terms of throughput and average latency, although the model accuracy was sufficiently high (R² = 0.8+). Post hoc analysis indicates that limited and occasionally stale runtime features caused the load balancer to direct all requests to a single container until the next statistics update, since that container was considered the ‘best’ during that interval. Full article

MicroRNAs are key post-transcriptional regulators in breast cancer, but their time-dependent dynamics and downstream oncogenic effects are not fully understood. miR-548c-3p has been proposed as a tumor suppressor, yet its temporal behavior and impact on cell cycle drivers remain unclear. This study investigated the time-dependent expression of miR-548c-3p and its post-transcriptional regulation of E2F3 and FOXM1 in MCF-7 breast cancer cells. Cells were analyzed at multiple time points (2–72 h) by quantitative real-time PCR to assess dynamic changes in miR-548c-3p, E2F3, and FOXM1 mRNA levels. Bioinformatic validation using TCGA-BRCA datasets and public platforms evaluated gene expression, promoter methylation, and prognostic significance. miR-548c-3p showed a progressive time-dependent decline, with the lowest levels at 72 h, whereas E2F3 and FOXM1 were significantly upregulated over time, supporting a post-transcriptional derepression mechanism. TCGA-based analyses confirmed overexpression and hypomethylation of E2F3 and FOXM1 in breast cancer, particularly in triple-negative tumors, and high expression of both genes was associated with poor survival. These findings indicate that time-dependent loss of miR-548c-3p contributes to E2F3 and FOXM1 activation through a post-transcriptional regulatory mechanism, highlighting this miRNA–oncogene axis as a potential prognostic signature and therapeutic target in breast cancer. Full article

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an immune-mediated neurological disorder driven by dysregulated neuroimmune interactions, yet the molecular architecture linking tumor-associated immune activation, peripheral immunity, and neuronal dysfunction remains insufficiently understood. In this study, we established an integrative computational framework that combines multi-tissue transcriptomic profiling, weighted gene co-expression network analysis, immune deconvolution, and machine learning-based feature prioritization to systematically characterize the regulatory landscape of the disease. Joint analysis of three independent GEO datasets spanning ovarian teratoma tissue and peripheral blood transcriptomes identified 2001 consistently dysregulated mRNAs, defining a shared tumor–immune–neural transcriptional axis. Across multiple feature selection algorithms, ACVR2B and MX1 were reproducibly prioritized as immune-associated candidate genes and were consistently downregulated in anti-NMDAR encephalitis samples, showing negative correlations with neutrophil infiltration. Reconstruction of an integrated mRNA-miRNA-lncRNA regulatory network further highlighted a putative core axis (ENSG00000262580–hsa-miR-22-3p–ACVR2B), proposed as a hypothesis-generating regulatory module linking non-coding RNA regulation to immune-neuronal signaling. Pathway and immune profiling analyses demonstrated convergence of canonical immune signaling pathways, including JAK-STAT and PI3K-Akt, with neuronal communication modules, accompanied by enhanced innate immune signatures. Although limited by reliance on public datasets and small sample size, these findings delineate a systems-level neuroimmune regulatory program in anti-NMDAR encephalitis and provide a scalable, network-based multi-omics framework for investigating immune-mediated neurological and autoimmune disorders and for guiding future experimental validation. Full article

Sex-specific factors can influence the onset and progression of osteoarthritis (OA), yet the molecular mechanisms underlying their impact remain poorly defined. This study investigated whether plasma microRNAs (miRNAs) correlate to sex-dependent OA progression, based on evidence of enhanced spontaneous osteoclastogenesis in peripheral blood mononuclear cells (PBMCs) derived from OA patients. miRNAs were evaluated on OA-plasma (n = 20 men, 20 women with knee OA; KL grade I–II) and their role on OA signaling was investigated through bioinformatic analysis. Seven miRNAs were identified as significantly upregulated in men’ vs. women’ samples: hsa-miR-107, hsa-miR-23a-3p, hsa-miR-103a-3p, hsa-let-7g-5p, hsa-miR-22-3p, hsa-miR-106a-5p, hsa-miR-142-3p, and were associated with OA-related tissues and pathways. Notably, two common targets were identified: Adenosine Triphosphate Citrate Lyase (ACLY), a key enzyme linking citrate metabolism to epigenetic regulation, and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), a component of the phosphatidylinositol-3-kinase PI3K/AKT/mTOR pathway. In men, increased miRNA expression may repress ACLY and PIK3R1, affecting catabolic gene expression, inflammation, and OA progression. Conversely, their lower expression in women may mitigate these effects by counterbalancing the OA-promoting influences driven by sex hormones. A functional validation is needed to confirm miRNA–ACLY/PIK3R1 interactions and their sex-specific roles in early OA pathophysiology. Full article

Background/Objectives: Testicular toxicity is one of the most important chemotherapeutic adverse effects of Cisplatin (Cisp), which restricts its use and effectiveness. This study investigated the preventive effects of Vitis vinifera L. extract on Cisp-induced testicular injury in rats. Methods: Forty adult albino male rats were allocated into four groups: control, Vitis vinifera L. extract, Cisp, and co-treated (Vitis vinifera L. extract + Cisp). Sperm motility and count, serum reproductive hormones, oxidative/antioxidant biomarkers, pro-inflammatory cytokines, ferroptosis biomarkers, and gene expression profiles were evaluated. Results: Cisp administration markedly impaired reproductive performance, as evidenced by significant declines in serum FSH, LH, testosterone, and sperm motility and count. Cisp also induced oxidative stress by elevating MDA, GSSG, GPx, and 8-OHdG, while reducing SOD, Catalase, NRF2, and Ho-1 along with total and reduced GSH levels. Moreover, it triggered strong inflammatory responses and ferroptosis activation, with notable up-regulation of NFκB, TNF-α, IL-1β, ferritin, and cathepsin. Gene expression analysis revealed down-regulation of ARNTL, PI3K, and miR-125b and up-regulation of ASCL4, GSK3B, and COX2 following Cisp exposure. Conversely, co-treatment with Vitis vinifera L. extract significantly ameliorated these alterations, restoring sperm quality, hormone balance, antioxidant defenses, and modulating inflammatory, ferroptosis, and genetic responses toward normalcy in addition to restoring testicular and epididymal histoarchitecture without any significant effect in NRF2 and ARNTL expression. Additionally, co-treated groups with Vitis vinifera L. extract showed a significant decline in NF-kB p65 and increased PCNA testicular immunoreactivity with a substantial down-regulation in NF-kB p65 and PCNA epididymal immunoreactivity. Vitis vinifera L. extract alone did not affect any studied parameters as compared to the control group. Conclusions: These findings suggested that Vitis vinifera L. extract has a significant protective effect against Cisp-related testicular injury through antioxidative, anti-inflammatory, and anti-ferroptotic mechanisms. Full article