Search Results (597)

Let ${\mathcal{R}}_{LP}$ denote a newly introduced subclass of bounded turning functions. The primary aim of this study is to investigate the sharp bounds of the coefficients of $|d_2|,|d_3|,|d_4|,|d_5|$, as well as to establish precise estimates for the second- and third-order Hankel determinants $H_{2,1},H_{2,2},H_{2,3}$, and $H_{3,1}$ for functions belonging to this class. The coefficient bounds and Hankel determinant estimates derived herein are all shown to be sharp. Full article

Let p be a prime number and m be a positive integer. In this paper, we investigate cyclic codes of length n over the local non-Frobenius ring $R=GR(p^2,m)\left[u\right]$, where $u^2=0$ and $pu=0$. We first determine the algebraic structure of cyclic codes of arbitrary length n. For the case $\gcd (n,p)=1$, we explicitly describe the generators of cyclic codes over R. Moreover, we establish necessary and sufficient conditions for the existence of self-dual and LCD codes, together with their enumeration. Several illustrative examples and tables are presented, highlighting the mass formula for cyclic self-orthogonal codes, cyclic LCD codes, and families of new cyclic codes that arise from our results. Full article

Objective: This study aimed to elucidate the regulatory mechanisms of the long intergenic non-protein coding RNA 02381 (LINC02381)/microRNA-let-7g-5p (let-7g-5p)/thrombospondin 1 (THBS1) signaling axis in osteosarcoma (OS). Methods: The expression levels of LINC02381, let-7g-5p, and THBS1 were quantified in OS and adjacent normal tissues via reverse transcription quantitative polymerase chain reaction. Their correlations with clinicopathological features were analyzed. Expression patterns were further validated in OS cell lines (143B, U-2OS, Saos-2, MNNG-HOS, MG-63) and normal osteoblast cell line hFOB1.19. The molecular interaction between LINC02381 and let-7g-5p and the targeting relationship of let-7g-5p with THBS1 were verified via dual-luciferase reporter and RNA pull-down assays. Functional effects were assessed using cell counting kit-8, colony formation, Transwell migration, and xenograft tumor models. Results: Compared to adjacent normal tissues, LINC02381 and THBS1 were upregulated in OS tissues (fold change > 3.0, p < 0.001), while let-7g-5p was downregulated (fold change ≈ 0.038, p < 0.001). Similar expression trends were observed in U-2OS cells. Knockdown of LINC02381 or overexpression of let-7g-5p reduced cell proliferation, colony formation, migration, THBS1 expression, and tumor volume (p < 0.001). These inhibitory effects were partially reversed by let-7g-5p inhibitors, restoring cell viability and migration by approximately 70%. Mechanistically, LINC02381 functioned as a competing endogenous RNA (ceRNA), directly binding to let-7g-5p and mitigating its suppression of THBS1. Conclusions:LINC02381 promotes OA progression by acting as a ceRNA for let-7g-5p, thereby upregulating THBS1 expression. This signaling axis represents a potential therapeutic target for OS. Full article

Intracranial aneurysms (IAs) are potentially devastating cerebrovascular lesions, and predicting rupture risk remains a major clinical challenge. Conventional radiological and clinical scores offer only partial risk stratification, highlighting the need for complementary approaches. Liquid biopsy represents a promising non-invasive strategy to identify circulating biomarkers that reflect aneurysm biology and instability. We conducted a systematic review according to PRISMA 2020 guidelines, screening PubMed, Scopus, and Web of Science up to August 2025. Forty-eight eligible studies, encompassing 3515 IA patients, evaluated circulating RNA species, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in serum, plasma, blood, or cerebrospinal fluid. Multiple candidates emerged as consistently dysregulated: upregulation of miR-21, miR-126, and miR-200a-3p, and downregulation of miR-143 and let-7b-5p were recurrently observed across independent cohorts. LncRNAs, such as MALAT1 and MIAT, and circRNAs, including circ_0000690 and circ_0021001, demonstrated diagnostic and prognostic potential, with some correlating with rupture status and clinical severity indices. Despite encouraging findings, heterogeneity in study design, sample handling, and analytic methods limits reproducibility. Large-scale, multicenter validation studies are essential to translate these biomarkers into clinical practice. Full article

Background/Objectives: To investigate microRNA (miRNA) expression profiles in the anterior lens capsules of patients with glucocorticoid-induced cataracts (GIC) and to identify miRNAs potentially associated with glucocorticoid (GC) exposure and posterior subcapsular cataract (PSC) formation. Methods: A total of 33 participants were divided into four groups based on their GC usage history and cataract type: GIC (n = 10), age-related PSC (n = 6), GC-treated age-related cataract (ARC) (n = 7), and normal control (n = 10). Anterior lens capsule samples were obtained during cataract surgery and total RNA was extracted for quantitative real-time polymerase chain reaction (qRT-PCR). The expression levels of 12 selected miRNAs were quantified using a customized miScript miRNA PCR array. Results: Among the twelve miRNAs analyzed, seven (let-7a-5p, let-7d-5p, miR-15a-5p, miR-16-5p, miR-23b-3p, miR-26a-5p, and miR-125a-5p) were significantly differentially expressed among the groups (p < 0.05). In the GIC group, let-7a-5p, miR-23b-3p, miR-26a-5p, and miR-125a-5p were significantly upregulated, whereas let-7d-5p, miR-15a-5p and miR-16-5p were significantly downregulated compared to that in the normal control group. No significant differences in miRNA expression were observed between the GIC and age-related PSC groups or between the GIC and GC-treated ARC groups. Conclusions: This study demonstrates distinct miRNA expression patterns in the anterior lens capsules of patients with GIC. Altered expression of specific miRNAs may be linked to the pathogenesis of GC-induced PSC formation. These findings provide a molecular basis for further investigation into the regulatory roles of miRNAs in GC-associated cataracts. Full article

Alpine wetlands, key carbon sinks and biodiversity hubs, remain understudied, especially under climate change pressures. Hence, the present study was conducted to assess the variability in soil enzyme activity (SEA) and the carbon management index (CMI) and to utilize principal component analysis (PCA) to explore the variation and correlation between SEA and CMI as influenced by altitudinal gradients in alpine wetlands. This information is essential for exploring the impacts of soil degradation and guiding restoration efforts. The study was designed in blocks (catchments) with six altitudinal variations (from 2500 to 3155 m a.s.l), equivalent to alpine wetlands from three catchments (Senqunyane, Khubelu and Sani) as follows: Khorong and Tenesolo in Senqunyane; Khamoqana and Khalong-la-Lichelete in Sani; and Lets’eng-la-Likhama and Koting-Sa-ha Ramosetsana in Khubelu. The soil samples were collected in February 2025 (autumn season, i.e., wet season) at depths of 0–15 and 15–30 cm and analyzed for bulk density, texture, pH, electrical conductivity (EC), soil organic carbon (SOC), SEA, and carbon pools, and the CMI was computed following standard procedures. The results demonstrated that the soil was loam to sandy loam and was slightly acidic and non-saline in nature in the 0–15 cm layer across the wetlands. The significant decreases in SEA were 45.33%, 32.20% and 15.11% (p < 0.05) for dehydrogenase, fluorescein di-acetate and β-Galactosidase activities, respectively, in KSHM compared with those in Khorong (lower elevated site). The passive carbon pool (C_PSV) was dominant over the active carbon pool (C_ACT) and contributed 76–79% of the SOC to the total organic carbon, with a higher C_PSV (79%) observed at KSHM. The CMI was also greater (91.05 and 75.88) under KSHM at the 0–15 cm and 15–30 cm soil depths, respectively, than in all the other alpine wetlands, suggesting better carbon management at higher altitudinal gradients and less enzymatic activity. These trends shape climate change outcomes by affecting soil carbon storage, with high-altitude regions serving as significant, though relatively less active, carbon reservoirs. The PCA-Biplot graph revealed a negative correlation between the CMI and SEA, and these variables drove more variation across sites, highlighting a complex interaction influenced by higher altitude with its multiple ecological drivers, such as temperature variation, nutrient dynamics, and shifts in microbial communities. Further studies on metagenomics in alpine soils are needed to uncover altitude-driven microbial adaptations and their role in carbon dynamics. Full article

Let ${\lambda }_1,{\lambda }_2,{\lambda }_3$ be nonzero real numbers, not all of the same sign; let ${\lambda }_1/{\lambda }_2$ be irrational; and let $\eta$ be any real number. We investigate the solvability of the inequality $|{\lambda }_1{p}_1+{\lambda }_2{p}_2+{\lambda }_3{p}_3^2+\eta |<{\left(\max p_j\right)}^{-1/12+\theta }$, $\theta >0$ in the prime variables $p_1$, $p_2$, and $p_3$. We require that $p_1+2$ and $p_2+2$ have no more than 20 prime factors, while $p_3+2$ has no more than 42 prime factors. Full article

Heart failure (HF) is a complex and multifactorial syndrome with high morbidity and mortality rates worldwide. Accumulative evidence suggests that microRNAs (miRNAs) play critical roles in maintaining cardiac homeostasis. The dysregulation of various miRNAs has been reported in different studies on failing human hearts. However, little is known about their circulatory profile. In this study, comprehensive miRNA profiling was performed by next-generation sequencing for plasma samples of 24 HF and 24 age and sex-matched, non-HF patients. A total of 1391 miRNAs were detected, of which 228 miRNAs and 261 miRNAs were commonly expressed in the HF and non-HF groups, respectively. Eight miRNAs (hsa-let-7b-3p, hsa-miR-92b-5p, hsa-miR-145-3p, hsa-miR-206, hsa-miR-664a-5p, hsa-miR-1307-5p, hsa-miR-1908-5p, and hsa-miR-3074-5p) were found to be dysregulated between HF and non-HF patients. The expression of another seven miRNAs (hsa-miR-589-5p, hsa-miR-30b-5p, hsa-miR-654-3p, hsa-miR-1292-5p, hsa-miR-659-5p, hsa-miR-548d-5p, and hsa-miR-7847-3p) was frequently observed in HF patients but not in non-HF cases. Subsequent analyses of target gene prediction and associated pathways revealed the enrichment of pathways related to vascular development, the cell cycle, and transcriptional activity. These data reveal the expression profile and the dysregulation of circulating miRNAs in our patients with HF. Full article

Network reliability refers to a probabilistic measure of a network system’s ability to maintain its intended service functionality within a specified time interval and under given operating conditions. Let $\Omega (n,m)$ be the set of all simple two-terminal networks on n vertices and m edges. If each edge operates independently with the same fixed probability $p\in [0,1]$, then the two-terminal reliability, denoted by $R_2(G,P))$, is the probability that there exists a path between two target vertices s and t. For a given number of vertices n and edges m, there are some graphs within $\Omega (n,m)$ that have higher reliability than others, and these are known as extremely optimal graphs. In this work, we determine the sets of extremely optimal graphs in two classes of two-terminal network with sizes $m={\displaystyle \frac{n(n-1))}{2}}-2$ and $m={\displaystyle \frac{n(n-1))}{2}}-3$, consisting of 2 and 5 networks, respectively. Moreover, we identify one class of graphs obtained by deleting some edges among non-target vertices in the complete two-terminal graph, and we count the number of graphs of this class with size ${\displaystyle \frac{n(n-1)}{2}}-\lfloor {\displaystyle \frac{n-2}{2}}\rfloor \le m\le {\displaystyle \frac{n(n-1))}{2}}-1$ by applying the Pólya counting principle. Full article

Ovarian cancer (OvCa) is one of the most life-threatening female malignancies that affects 300,000 women annually worldwide. Impaired mechanisms of DNA repair are the leading cause of mutations underlying the OvCa development. microRNAs are short non-coding RNAs that regulate the expression of genes by binding to their transcripts and inducing mRNA degradation or inhibition of translation. Here, we review the miRNA-mediated dysregulation of genes involved in DNA damage response (DDR) and DNA repair pathways in OvCa. Apparently, miRNAs are capable of targeting the crucial mediators of DDR (e.g., miR-203a-3p targeting ATM (Ataxia Telangiectasia Mutated)), homologous repair (such as BRCA1 targeted by miR-9, miR-1255b, miR-193b, and miR-148b), non-homologous end joining (with RNF8 being regulated by miR-214), nucleotide excision repair (involving DDB2 targeted by miR-328-3p), or translesion DNA synthesis (involving RAD18, participating also in homologous repair and targeted by miR-379-5p). We also discuss miRNAs (such as miR-519a-3p, let-7e, miR-216b), which affect responses to OvCa therapy by targeting PARP1 (Poly(ADP-Ribose) Polymerase-1). Finally, we also discuss why, despite the identification of multiple miRNAs capable of regulating DNA repair genes, as well as those involved in the response to therapy, no miRNA-based drugs have been approved for OvCa treatment in clinics. Full article

Chronic obstructive pulmonary disease (COPD) involves persistent inflammation and dysregulated lipid metabolism, with foamy macrophages playing a central role in disease progression. Exosomes—vesicles transporting microRNAs (miRNAs)—mediate intercellular communication, but their contribution to foamy macrophage-driven COPD remains unclear. This study investigates the role of exosomal miRNAs, particularly let-7, in modulating lipid metabolism and inflammation in foamy macrophages. Bone marrow-derived macrophages (BMDMs) were treated with oxidized low-density lipoprotein (oxLDL) and lipopolysaccharide (LPS) to induce foamy macrophage formation. Exosomal miRNA profiles were analyzed, and the function of let-7c-3p was assessed via transfection. Foamy macrophages released significantly more exosomes (392.7 × 10⁷ particles) than controls (284.9–302.5 × 10⁷), without differences in exosome size or molecular content. The miRNA sequencing and qRT-PCR confirmed downregulation of exosomal let-7c-3p in foamy macrophages, correlating with increased RNF8 and decreased RXR expression—markers of disrupted PPAR/RXR signaling. Pathway analysis implicated let-7c-3p in regulating PPAR/RXR, WNT/β-catenin, and pulmonary fibrosis pathways. Transfection with let-7 mimics reduced lipid accumulation (52% to 19%), suppressed RNF8, restored RXR, and lowered IL-6 and TNF-α levels, indicating strong anti-inflammatory and lipid-modulating effects. Loss of exosomal let-7c-3p aggravates lipid dysregulation and inflammation in COPD by impairing PPAR/RXR signaling. Restoring let-7 expression reverses these effects, highlighting its potential as a diagnostic biomarker and therapeutic target. Full article

Oxidative stress destabilizes microRNA homeostasis in the retinal pigment epithelium (RPE), driving apoptosis and the epithelial-to-mesenchymal transition, which contribute to age-related macular degeneration. We investigated whether Quantum Molecular Resonance (QMR^®) electrostimulation, alone or combined with Patient Blood-Derived (PBD) secretoma, can reprogram the RPE miRNome and mitigate stress-induced damage. Human ARPE-19 cells were exposed to tert-butyl-hydroperoxide and treated with QMR^®, PBD secretome, or their combination. The deep sequencing of small RNAs at 24 h and 72 h, followed by differential expression and pathway enrichment analyses, delineated treatment-driven miRNA signatures. Oxidative stress deregulated > 50 miRNAs, enriching pro-apoptotic, fibrotic, and inflammatory pathways. QMR^® restored roughly 40% of these miRNAs and upregulated additional cytoprotective species such as miR-590-3p, a known regulator of the NF-κB and NLRP3 pathways according to validated target databases. While these observations suggest the potential involvement of inflammatory and stress-related cascades, functional assays will be required to directly confirm such effects. Secretome treatment preferentially increased anti-inflammatory miR-146a-5p and regenerative miR-204-5p while suppressing pro-fibrotic let-7f-5p. Combined QMR^® + secretome triggered the broadest miRNA response, normalizing over two-thirds of stress-altered miRNAs. These changes are predicted to influence antioxidant, anti-apoptotic, and anti-fibrotic pathways, although they did not translate into additional short-term cytoprotection compared with QMR^® alone. These data indicate that QMR^® and PBD secretome modulate complementary miRNA programs that converge on stress response networks. This broader molecular reprogramming may reflect regulatory complementarity, but functional validation is needed to determine whether it provides benefits beyond those observed with QMR^® alone. These findings offer molecular insights into potential non-invasive, cell-free strategies for retinal degeneration, although in vivo validation will be required before any clinical translation to Age-Related Macular Degeneration (AMD) therapy. Full article

Background: Despite clinical and pathological risk tools, predicting outcomes in non-muscle-invasive bladder cancer (NMIBC), particularly high-grade (HG) cases, remains challenging due to its unpredictable recurrence and progression. There is an urgent need for molecular biomarkers to enhance risk stratification and guide treatment. Methods: We assessed the prognostic potential of eight miRNAs (miR-9, miR-143, miR-182, miR-205, miR-27a, miR-369, let-7c, and let-7g) in a cohort of ninety patients with primary bladder cancer. Expression data were retrieved from our previously published studies. Kaplan–Meier’s and Cox’s regression analyses were used to evaluate the associations with overall survival (OS), metastasis-free survival (MFS), and clinical outcomes. Principal component analysis (PCA) was performed to identify informative miRNA combinations. Target gene prediction, pathway enrichment (DAVID), and drug–gene interaction mapping (DGIdb) were conducted in silico. Results: A high expression of let-7g and miR-9 was significantly associated with better OS in HG NMIBC and MIBC, respectively (p = 0.013 and p = 0.000). MiR-9 downregulation correlated with metastasis in MIBC (p = 0.018). Among all combinations, miR-205 and miR-27a best predicted intermediate-risk NMIBC progression and recurrence (r² = 0.982, p = 0.000). A functional analysis revealed that these miRNAs regulate key cancer-related pathways (MAPK, mTOR, and p53) through genes such as TP53, PTEN, and CDKN1A. Drug interaction mapping identified nine target genes (e.g., DAPK1, ATR, and MTR) associated with eight FDA-approved bladder cancer therapies, including cisplatin and gemcitabine. Conclusions: Let-7g, miR-9, miR-143, miR-182, and miR-205 emerged as promising biomarkers for outcome prediction in NMIBC. Their integration into liquid biopsy platforms could support non-invasive monitoring and personalized treatment strategies. These findings warrant validation in larger, prospective studies and through functional assays. Full article

Background: Freeze tolerance is an uncommon but highly effective strategy that allows certain vertebrates to survive prolonged exposure to subzero temperatures in a frozen, ischemic state. While past studies have characterized the metabolic and biochemical adaptations involved, including cryoprotectant accumulation and metabolic rate suppression, the contribution of post-transcriptional gene regulation by microRNAs (miRNAs) remains largely unexplored. This study investigated freeze-responsive miRNAs in cardiac tissue of the gray tree frog, Dryophytes versicolor, to better understand the molecular mechanisms that support ischemic survival and tissue preservation. Methods: Adult frogs were subjected to controlled freezing at −2.5 °C, and cardiac tissue was collected from frozen and control animals. Total RNA was extracted and analyzed via small RNA sequencing to identify differentially expressed miRNAs, followed by target gene prediction and KEGG pathway enrichment analysis. Results: A total of 3 miRNAs were differentially expressed during freezing, with significant upregulation of miR-93-5p and let-7b-5p and downregulation of miR-4485-3p. Predicted targets of upregulated miRNAs included genes involved in immune signaling pathways (e.g., cytokine–cytokine receptor interaction), steroid hormone biosynthesis, and neuroactive ligand–receptor interaction, suggesting suppression of energetically costly signaling processes. Downregulation of miRNAs targeting cell cycle, insulin signaling, and WNT pathways indicates possible selective preservation of cytoprotective and repair functions. Conclusion: Overall, these results suggest that D. versicolor employs miRNA-mediated regulatory networks to support metabolic suppression, maintain essential signaling, and prevent damage during prolonged cardiac arrest. This work expands our understanding of freeze tolerance at the molecular level and may offer insights into biomedical strategies for cryopreservation and ischemia–reperfusion injury. Full article

Background/Objectives: Despite the significant advancements made in the diagnosis of lung cancer, the traditional diagnostic methods remain limited because they are often invasive, expensive, and not suitable for regular screening, creating a need for more accessible and non-invasive alternatives. In this context, the analysis of miRNAs in EVs and free circulating microRNA may be used as liquid biopsies in lung cancer to identify individuals at risk. This study aimed to compare miRNA profiles in the serum and EVs derived from lung cancer patients by focusing on Let-7a-5p and miR-21-3p. Materials and Methods: Serum and EVs were isolated from lung cancer patients and healthy controls. EVs were characterized using nanoparticle tracking analysis, electron microscopy, and Western blotting for surface markers (CD63, CD81, TSG101). Total miRNA levels were quantified in the serum and EVs, and specific miRNAs (hsa-let-7a-5p and hsa-miR-21-3p) were analyzed using RT-qPCR. Statistical analysis evaluated miRNA expression across clinicopathological features, including age, gender, smoking status, tumor stage, cancer type, and EGFR mutation status. Results: Total miRNA levels were significantly enriched in EVs compared to the serum. Let-7a-5p was downregulated in EVs from patients with advanced-stage lung cancer (Stage III–IV) compared to those with early-stage cancer and controls (p < 0.05), while no differences were observed in the serum. Conversely, miR-21-3p was significantly upregulated in EVs and serum from advanced-stage patients (p < 0.01) and in adenocarcinoma compared to squamous cell carcinoma (p < 0.05). No significant differences were observed for age, gender, or smoking status. Conclusions: Our findings highlight the differential expression of miRNAs in EVs and the serum, emphasizing the diagnostic potential of EV-associated Let-7a-5p and miR-21-3p in lung cancer. These results suggest that EVs are a more robust source for miRNA biomarkers compared to the serum. Full article