Search Results (1,205)

MicroRNA (miRNA), as a key post-transcriptional regulatory factor, plays a crucial role in embryonic development. The coordination of endoderm cell convergence and cardiac precursor cell (CPC) migration is critical for cardiac tube fusion. Defects in endoderm can impair the normal migration of CPCs towards the midline, leading to cardia bifida. Although the role of the microRNA-183 family (miR-183, miR-96 and miR-182) in cardiovascular diseases has been reported, the mechanism by which they regulate early heart development remains unclear. In this study, we used zebrafish as a model to elucidate the roles of the microRNA-183 family in early heart development. miRNA mimics were injected into Tg (cmlc2: eGFP) and Tg (sox17: eGFP) transgenic embryos to overexpress the miR-183 family. The results showed that, at 36 hpf, single or co-injection of miR-183/96/182 mimics caused defects in endoderm convergence, with a hole in the endoderm, and a significant down-regulation of the endoderm marker gene sox32. Additionally, embryos with single or co-injection of miR-183/96/182 mimics exhibited cardia bifida and tail blisters, with significantly down-regulated expression levels of genes related to heart development, including cmlc2, vmhc, amhc, nppa, gata4, gata5, nkx2.5, bmp2b, and bmp4. The phenotype caused by overexpression of the miR-183 family is highly consistent with loss of the sphingosine 1-phosphate receptor S1Pr2. Bioinformatics analysis result found that miR-183 can bind to 3′-UTR of the s1pr2 to regulate its expression; overexpression of miR-183 led to a significant decrease in the expression of the s1pr2 gene. Dual luciferase assay results suggest that s1pr2 is a bona fide target of miR-183. In summary, the miR-183 family regulates endoderm convergence and cardiac precursor cell migration via the S1Pr2 signaling pathway. This study reveals that the miR-183 family is a key regulatory factor in endoderm convergence and cardiac precursor cell migration during the early zebrafish development, elucidating the molecular mechanisms underlying early cardiac precursor cell and endoderm cell movement. Full article

Background/Objectives: Spheroid cultures in Matrigel are routinely used to study cell behaviour in complex 3D settings, thereby generating preclinical models of disease. Ideally, researchers would like to modulate gene expression ‘in situ’ for testing novel gene therapies while conserving the spheroid architecture. Here, we aim to provide an efficient method to transfect small RNAs (such as microRNAs and small interfering RNAs, i.e., siRNAs) into human induced pluripotent stem cell (iPSC)-derived 3D lung spheroids, specifically alveolar type II epithelial cells (iAT2) and basal cell (iBC) spheroids. Methods: Transfection of iAT2 spheroids within 3D Matrigel ‘in situ’, whole spheroids released from Matrigel or spheroids dissociated to single cells was explored via flow cytometry using a fluorescently labelled siRNA. Validation of the transfection method was performed in iAT2 and iBC spheroids using siRNA and miRNA mimics and measurement of specific target expression post-transfection. Results: Maximal delivery of siRNA was achieved in serum-free conditions in whole spheroids released from the Matrigel, followed by whole spheroids ‘in situ’. ‘In situ’ transfection of SFTPC-siRNA led to a 50% reduction in the SFTPC mRNA levels in iAT2 spheroids. Transfection of miR-29c mimic and miR-21 pre-miR into iAT2 and iBC spheroids, respectively, led to significant miRNA overexpression, together with a significant decrease in protein levels of the miR-29 target FOXO3a. Conclusions: This study demonstrates successful transfection of iPSC-derived lung spheroids without disruption of their 3D structure using a simple and feasible approach. Further development of these methods will facilitate functional studies in iPSC-derived spheroids utilizing small RNAs. Full article

Immune dysregulation presents a significant clinical challenge due to its rapid progression and complex interplay between hyperinflammatory and immunosuppressive responses. Different responses from the innate and adaptive immune systems can result in diseases such as immunoparalysis, cytokine storms, and secondary infections. Current diagnostic methods remain non-specific and time-consuming, delaying targeted interventions. A compartmentalized approach to immune monitoring, distinguishing innate and acquired immune response functional differentiation, is essential for distinguishing between hyperactivation and suppression. Key biomarkers, including cytokines, Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), and CD4/CD8 counts, as well as Programmed Death Ligand-1 (PDL-1) and V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) regulators, can guide personalized treatment strategies. Although they need more clinical validation, novel therapeutic methods such as cytokine inhibitors, immunological stimulants, and immunomodulators have demonstrated promise. Early diagnosis and precision medicine developments could lead to better patient outcomes. Advances in non-coding RNAs have led to specific diagnostic panels based on microRNA (MiRNA) levels. A deeper understanding of immune imbalance in sepsis is critical for optimizing treatment and reducing mortality rates. This review highlights emerging diagnostic and therapeutic strategies to address the multifaceted nature of sepsis-related immune dysregulation. Full article

Background: Managing hypercholesterolemia is essential for reducing health risks and costs. Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors are recommended for patients with high low-density lipoprotein cholesterol (LDL-C) levels at risk for cardiovascular disease, especially those on maximum doses of statins and ezetimibe. However, their cost-effectiveness is unclear, particularly in Saudi Arabia, where cardiovascular disease is prevalent. The main objective of this study was to evaluate the costs and outcomes of PCSK9 inhibitors versus statins and ezetimibe. Methods: A multicenter retrospective study reviewed charts of adults (≥18 years) with hypercholesterolemia treated with PCSK9 inhibitors (evolocumab or alirocumab) for at least 12 months. Outcomes included LDL-C reduction and cardiovascular-related hospitalizations, with direct medical costs estimated via micro-costing and adjusted for confounders. Results: The analysis included 118 patients on PCSK9 inhibitors and 304 on statins plus ezetimibe. Mean LDL-C reductions were 1.432 mmol/L [95% CI: 0.964 to 1.899] for PCSK9 inhibitors and 0.644 mmol/L [95% CI: 0.464 to 0.823] for the other group. Cardiovascular-related hospitalizations averaged 0.645 for PCSK9 inhibitors compared to 0.808 for statins plus ezetimibe. The annual cost for PCSK9 inhibitors ranged from USD 4024 [95% CI: 3786.80 to 7947.91] to USD 7559 [95% CI: 7331.35 to 11,509.66]. In 99.13% and 98.78% of bootstrap distributions, PCSK9 inhibitors led to greater LDL-C reductions and fewer hospitalizations. Conclusions: The use of PCSK9 inhibitors for managing hypercholesterolemia was associated with a greater reduction in LDL-C levels and fewer cardiovascular-related hospitalizations. However, the more modest LDL-C reduction compared to clinical trials, combined with the high acquisition cost of PCSK9 inhibitors, underscores the need to provide significant price reductions to improve patient access to these lipid-lowering agents. Full article

Vascular calcification (V) is an independent risk factor for all-cause and cardiovascular mortality. Vascular smooth muscle cells (VSMCs) play a major role in VC as they can acquire mineralizing properties when exposed to osteogenic conditions. Despite its clinical impact, there are still no dedicated therapeutic strategies targeting VC. To address this issue, we used human calcified and non-calcified atherosclerotic arteries (ECLAGEN Biocollection) to screen and identify microRNA (miR) associated with VC. We combined non-biased miRNomic (microfluidic arrays) and transcriptomic analysis to select miR candidates and their putative target genes with expression associated with VC and ossification. We further validated miR functional regulation and function in relation to cell mineralization using primary human VSMCs. Our study identified 12 miRs associated with VC in carotid and femoral arteries. Among those, we showed that miR136, miR155, and miR183 expression were regulated during VSMC mineralization and that overexpression of these miRs promoted VSMC mineralization. Cross-analysis of this miRNomic and a transcriptomic analysis led to the identification of CD73 and Smad3 pathways as putative target genes responsible for mediating the miR155 pro-mineralizing function. These results highlight the potential benefit of miR155 inhibition in limiting VC development in peripheral atherosclerotic arteries. Full article

Community-Based Tourism (CBT) refers to forms of tourism owned and managed by local communities, designed to enhance participation, empowerment, and equitable benefit-sharing. This study investigates how climate-induced migration and donor investment disparities shape the uneven development of CBT across Vietnam. The research pursues three aims: (1) to evaluate how macro- and micro-level funding structures influence CBT readiness; (2) to analyze how spatial justice and post-development critique illuminate structural inequalities in tourism investment; and (3) to assess the implications for climate-vulnerable and ethnic minority communities, including their underrepresentation in CBT research and policy discourse. Methodologically, the study undertakes a systematic review of CBT literature (2014–2025), a thematic analysis of donor and government reports (World Bank, ADB, IFAD), and an estimation of regional funding flows using narrative coding and text-based pattern analysis. Findings reveal a persistent geographic and institutional bias toward the Southern Mekong Delta, which benefits from climate-resilience projects and tourism-specific investments, while Northern Highlands regions remain marginalized, receiving only poverty-focused funding. The paper contributes by integrating spatial justice and post-development critique into tourism studies, demonstrating how donor-led “resilience” agendas can inadvertently reinforce spatial inequalities, and offering policy recommendations for more equitable CBT planning, funding, and scholarly attention across Vietnam’s diverse regions. Full article

Beyond well-known genetic drivers, microRNA dysregulation has emerged as a key contributor to thyroid tumorigenesis. Central to this process is Dicer1, a ribonuclease essential for microRNA maturation, whose expression is often reduced in papillary thyroid carcinoma (PTC). Evidence from previous studies suggest Dicer1 functions as a context-dependent haplo-insufficient tumor suppressor gene: partial loss may promote tumor development, whereas complete loss may disrupt essential cellular functions, causing cell death and tumor suppression. However, the effects of partial or complete Dicer1 loss in thyroid cancer remain unclear. To explore this, we genetically inactivated one (heterozygous) or both (homozygous) Dicer1 alleles specifically in thyroid follicular cells of a RET/PTC3 transgenic mouse model using an inducible Cre-Lox system. Our findings deepen the current understanding of the RET/PTC3-driven PTC model by revealing an increased number of vimentin-positive cells and disruption in redox homeostasis. Additionally, whereas heterozygous Dicer1 loss did not alter tumor progression in RET/PTC3 mice, total loss reduced tumor growth and led to accumulated DNA damage and cell death. These findings highlight the crucial role of Dicer1 dosage in thyroid cancer progression and underscore its potential as a therapeutic target for aggressive PTC and other malignancies characterized by aberrant Dicer1 expression. Full article

Background/Objectives: Urothelial bladder carcinoma (UBC) is one of the most prevalent malignancies worldwide, and efforts have intensified to identify molecular markers that improve the prognosis and reduce treatment costs. Among the regulators of tumor behavior, microRNAs (miRNAs) have emerged as promising biomarkers for cancer diagnoses and treatment. The modulation of miR-25-3p has been associated with pancreatic, colorectal, and lung cancers; its role in UBC remains poorly explored. In this study, we investigated the effects of miR-25-3p modulation in a high-grade and muscle-invasive bladder cancer (MIBC) cell line (T24), using in vitro functional assays and bioinformatics approaches. Results: Bioinformatics analyses using TCGA-BLCA datasets revealed that miR-25-3p is upregulated in tumor tissues compared to non-tumor tissues, prompting an investigation into its molecular targets and related pathways. The transfection of T24 cells with an miR-25-3p mimic and inhibitor led to respective overexpression (11.16-fold) and downregulation (-2.82-fold) compared to the negative control. Functionally, miR-25-3p overexpression increased cell proliferation, viability, and migration, while its inhibition decreased the cell migration capacity. A gene expression analysis revealed that miR-25-3p overexpression resulted in the downregulation of TP53, AIFM1, NFE2L2, TFRC, ACSL4, SLC7A11, and SLC3A2, whereas MMP9, MMP11, and GPX4 were upregulated, suggesting a role in both migration and ferroptosis regulation. In the inhibitor group, increased SLC3A2 and decreased MMP11 expression further supported this connection. Our results using an in vitro model for MIBC with the transfection of T24 cells suggest that miR-25-3p influences key pathways involved in oxidative stress and cell death, promoting a more aggressive tumor phenotype. Conclusions: The modulation of miR-25-3p impacts the behavior of T24 bladder cancer cells and may indicate its role in disease progression. Our results underscore the potential of miR-25-3p as a prognostic biomarker and support further studies considering its therapeutic relevance in managing high-grade and muscle-invasive bladder cancer. Full article

As the global demand for clean and efficient energy continues to grow, the development of advanced energy storage technologies is becoming increasingly important. This study explores the influence of the dead volume coefficient and pulse-width modulation (PWM) control strategy on the performance of a piston expander in a micro-compressed air energy storage system. Simulation results showed that low dead volume values, combined with short air supply durations with PWM values between 0.1 and 0.2, led to improved energy utilization. This was achieved through complete piston strokes and stable power output. In contrast, high dead volume values and high PWM settings, such as 0.9, resulted in incomplete air expansion, excessive air consumption, and a significant reduction in overall system efficiency, even though peak power output may increase. Sensitivity analysis confirmed that PWM had a major impact on efficiency, with the highest value of 0.76 achieved for a dead volume coefficient of 0.05 and a PWM value of 0.2. Under these operating conditions, the expander delivered a generated power output of 970 W. Additionally, PWM enabled flexible control of power output, without requiring modifications to the system’s physical design. The study highlights the importance of adjusting the air admission strategy to match the internal volume characteristics. Full article

Cutaneous melanoma is an aggressive form of skin cancer and a leading cause of cancer-related mortality. In this sense, Raman Spectroscopy (RS) could represent a fast and effective method for melanoma-related diagnosis. We therefore introduced a new method based on RS to distinguish Compound Naevi (CN) from Primary Cutaneous Melanoma (PCM) from ex vivo solid biopsies. To this aim, integrating Confocal Raman Micro-Spectroscopy (CRM) with four Machine Learning (ML) algorithms: Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), Support Vector Machine (SVM), and Random Forest Classifier (RFC). We focused our attention on the comparison between traditional pre-processing operations with Continuous Wavelet Transform (CWT). In particular, CWT led to the maximum classification accuracy, which was ∼89.0%, which highlighted the method as promising in view of future implementations in devices for everyday use. Full article

The exposure parameters in stereolithography with liquid crystal display (SLA-LCD) influence the functional properties of photopolymers, which is particularly important for tribological applications. In this study, the influence of the exposure time of the layers (2–8 s) on the surface topography (ISO 25178), Brinell hardness (HB) and chemical structure (FTIR spectroscopy) of UV-cured resin samples is investigated. Both insufficient and excessive UV irradiation led to undesirable effects ranging from incomplete cross-linking and surface irregularities to excessive curing, micro-cracking and increased surface kurtosis (high Sku values). The most balanced mechanical and topographical performance was observed at a layer exposure time of 6 s, characterised by low Spk values, uniform surface texture and high cohesion between layers. FTIR analysis confirmed the progressive cross-linking with increasing exposure time. The results show that precise control of irradiation parameters enables optimisation of the interrelationships between microstructure, mechanical properties and surface functionality, which is critical for improving the durability and performance of components operating under boundary or mixed lubrication. Full article

The increasing demand on combustion-based micro-power generation systems, mainly due to the high energy density of hydrocarbon fuels, created a great opportunity to develop portable power devices, which can be applied on micro unmanned aerial vehicles, micro-satellite thrusters, or micro chemical reactors and sensors. Also, the need for better and cheaper communications networks and control systems has led space companies to invest in micro and meso satellites, such as CubeSat. In this study, we conducted a comprehensive and meticulous study of micro-combustion within wavy channel micro-propulsion systems, which can be applied on micro unmanned aerial vehicles or CubeSat. The primary objective was to gain a deeper comprehension of the dynamics within these complex non-linear geometries and analyze the effect of different materials on the combustion dynamics and propulsion efficiency. Full article

Laser powder bed fusion (L-PBF) enables the fabrication of complex lattice-type structures composed of thin struts, offering lightweight, high-strength advantages in aerospace and biomedical applications, among others. While extensive research has examined full lattices and process parameter effects individually, the combined influence of strut geometry, configuration, and processing conditions on mechanical properties remains less understood. This study investigates how the strut number, strut size, cross-sectional shape, and laser energy input affect the mechanical properties of thin-strut L-PBF tensile specimens. Ti-6Al-4V struts were designed and fabricated using an EOS M270 system using five linear energy density (LED) levels. The fabricated specimens were measured in porosity using micro-scaled computed tomography and further evaluated using a tensile tester. The results showed that increasing the strut number leads to significant reductions in tensile strength, even with the same overall cross-sectional area, especially at low LED levels. Size effects on mechanical strengths were observed, though mostly minimal, except at the smallest strut size, where defects tend to be more critical. Circular and square shapes performed similarly under general LED conditions; however, square struts exhibited inferior behavior at the lowest LED level. Overall, LED is the most influential factor, with the greatest tensile strength occurring near 0.2 J/mm; further decreasing or increasing the LED both increase the porosity, degrading mechanical strengths. Full article

This study advances alkali-activated cementitious materials (AACMs) by developing a ground-granulated blast furnace slag/high-calcium fly ash (GGBS/HCFA) composite that incorporates Tuokexun desert sand and by establishing a clear linkage between activator chemistry, mix proportions, curing regimen, and microstructural mechanisms. The innovation lies in valorizing industrial by-products and desert sand while systematically optimizing the aqueous glass modulus, alkali equivalent, HCFA dosage, and curing temperature/time, and coupling mechanical testing with XRD/FTIR/SEM to reveal performance–structure relationships under thermal and chemical attacks. The optimized binder (aqueous glass modulus 1.2, alkali equivalent 6%, and HCFA 20%) achieved 28-day compressive and flexural strengths of 52.8 MPa and 9.5 MPa, respectively; increasing HCFA beyond 20% reduced compressive strength, while flexural strength peaked at 20%. The preferred curing condition was 70 °C for 12 h. Characterization showed C-(A)-S-H as the dominant gel; elevated temperature led to its decomposition, acid exposure produced abundant CaSO₄, and NaOH exposure formed N-A-S-H, each correlating with strength loss. Quantitatively, acid resistance was weaker than alkali resistance and both deteriorated with concentration: in H₂SO₄, 28-day mass loss rose from 1.22% to 4.16%, with compressive/flexural strength retention dropping to 75.2%, 71.2%, 63.4%, and 57.4% and 65.3%, 61.6%, 58.9%, and 49.5%, respectively; in NaOH (0.2/0.5/0.8/1.0 mol/L), 28-day mass change was +0.74%, +0.88%, −1.85%, and −2.06%, compressive strength declined in all cases (smallest drop 7.77% at 0.2 mol/L), and flexural strength increased at lower alkalinity, consistent with a pore-filling micro-densification effect before gel dissolution/cracking dominates. Practically, the recommended mix and curing window deliver structural-grade performance while improving high-temperature and acid/alkali resistance relative to non-optimized formulations, offering a scalable, lower-carbon route to utilize regional desert sand and industrial wastes in durable cementitious applications. Full article

This study investigates how Iyengar yoga postures influence autonomic nervous system (ANS) activity by analyzing multimodal physiological signals collected via wearable sensors. The goal was to explore whether subtle postural variations elicit measurable autonomic responses and to identify which sensor features most effectively capture these changes. Participants performed a sequence of yoga poses while wearing synchronized sensors measuring electrodermal activity (EDA), heart rate variability, skin temperature, and motion. Interpretable machine learning models, including linear classifiers, were trained to distinguish physiological states and rank feature relevance. The results revealed that even minor postural adjustments led to significant shifts in ANS markers, with phasic EDA and RR interval features showing heightened sensitivity. Surprisingly, micro-movements captured via accelerometry and transient electrodermal reactivity, specifically EDA peak-to-RMS ratios, emerged as dominant contributors to classification performance. These findings suggest that small-scale kinematic and autonomic shifts, which are often overlooked, play a central role in the physiological effects of yoga. The study demonstrates that wearable sensor analytics can decode a more nuanced and granular physiological profile of mind–body practices than traditionally appreciated, offering a foundation for precision-tailored biofeedback systems and advancing objective approaches to yoga-based interventions. Full article