Search Results (2,261)

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a systemic ciliopathy resulting from loss-of-function mutations in the PKD1 and PKD2 genes, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC1 and PC2 regulate mechanosensation, calcium signaling, and key pathways controlling tubular epithelial structure and function. Loss of PC1/PC2 disrupts calcium homeostasis, elevates cAMP, and activates proliferative cascades such as PKA–B-Raf–MEK–ERK, mTOR, and Wnt, driving cystogenesis via epithelial proliferation, impaired apoptosis, fluid secretion, and fibrosis. Recent evidence also implicates novel signaling axes in ADPKD progression including, the Hippo pathway, where dysregulated YAP/TAZ activity enhances c-Myc-mediated proliferation; the stimulator of interferon genes (STING) pathway, which is activated by mitochondrial DNA release and linked to NF-κB-driven inflammation and fibrosis; and the TWEAK/Fn14 pathway, which mediates pro-inflammatory and pro-apoptotic responses via ERK and NF-κB activation in tubular cells. Mitochondrial dysfunction, oxidative stress, and maladaptive extracellular matrix remodeling further exacerbate disease progression. A refined understanding of ADPKD’s complex signaling networks provides a foundation for precision medicine and next-generation therapeutics. This review gathers recent molecular insights and highlights both established and emerging targets to guide targeted treatment strategies in ADPKD. Full article

The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies to personalized therapy. While thiopurine methyltransferase (TPMT) was initially the primary focus, the discovery of nudix hydrolase 15 (NUDT15) appears as a more comprehensive determinant of thiopurine intolerance. This review aims to consolidate and critically evaluate the advancement achieved in unraveling the biological mechanism and clinical significance of NUDT15 pharmacogenetics in thiopurine therapy. Foundational studies showed the vital role of NUDT15 in the detoxification of active thiopurines, with common genetic variants (for instance, p. Arg139Cys) significantly disrupting its activity, leading to the accumulation of toxic metabolites. Observational studies consistently associated NUDT15 variants with severe myelosuppression, notably in Asian populations. Recent randomized controlled trials (RCTs) confirmed that NUDT15 genotype-guided dosing effectively reduces thiopurine-induced toxicity without interfering with the therapeutic outcome. Despite these advancements, challenges remain present, including the incomplete characterization of rare variants, limited data in the diverse Asian populations, and the need for standardized integration with metabolite monitoring. In conclusion, NUDT15 pharmacogenetics is essential for improving patient safety and thiopurine dosage optimization in the treatment of ALL. For thiopurine tailored medicine to be widely and fairly implemented, future research should focus on increasing genetic data across different populations, improving the dose adjustment algorithm, and harmonizing therapeutic guidelines. Full article

Vaccinium oldhamii, a blueberry species native to Korea, is a deciduous shrub in the Ericaceae family. Its fruit possesses various pharmacological properties, including anti-inflammatory effects and potential for treating osteoporosis. This study evaluated the effects of five fertilization concentration levels using Multifeed 20 (N:P:K = 20:20:20) on the growth and physiological characteristics of one-year-old V. oldhamii container seedlings. Treatments included 0 g·L⁻¹ (control), 0.5, 1.0, 1.5, and 2.0 g·L⁻¹. Increases in stem thickness, root length, and total dry weight were observed in the control, 0.5, 1.0, and 1.5 g·L⁻¹ treatments, whereas growth declined at 2.0 g·L⁻¹. Mortality rates exceeded 15% at concentrations above 1.0 g·L⁻¹. Photosynthetic capacity and chlorophyll content increased with fertilization. However, while growth improved with increasing fertilizer up to a certain level, it declined at the highest concentration. A fertilization rate of 0.5 g·L⁻¹ proved to be the most economically and environmentally efficient for producing healthy seedlings. This study provides the first fertilization threshold for V. oldhamii, offering practical guidance for nursery production and forming a foundation for future domestication strategies. Full article

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with hypercholesterolemia identified as a major, but modifiable risk factor. This review serves as the second part of a comprehensive analysis of dyslipidemia management. The first installment laid the groundwork by detailing the key pathophysiological mechanisms of lipid metabolism, the development of atherosclerosis, major complications of hyperlipidemia, and the importance of cardiovascular risk assessment in therapeutic decision-making. It also examined non-pharmacological interventions and conventional therapies, with a detailed focus on statins and ezetimibe. Building upon that foundation, the present article focuses exclusively on emerging pharmacological therapies designed to overcome limitations of standard treatment. It explores the mechanisms, clinical applications, safety profiles, and pharmacogenetic aspects of novel agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab, evolocumab), small interfering RNA (siRNA) therapy (inclisiran), adenosine triphosphate–citrate lyase (ACL) inhibitor (bempedoic acid), microsomal triglyceride transfer protein (MTP) inhibitor (lomitapide), and angiopoietin-like protein 3 (ANGPTL3) inhibitor (evinacumab). These agents offer targeted strategies for patients with high residual cardiovascular risk, familial hypercholesterolemia (FH), or statin intolerance. By integrating the latest advances in precision medicine, this review underscores the expanding therapeutic landscape in dyslipidemia management and the evolving potential for individualized care. Full article

Background/Objectives: Myelodysplastic syndrome (MDS) is a heterogeneous clonal hematopoietic disorder characterized by ineffective hematopoiesis and leukemic transformation risk. Current therapies show limited efficacy, with ~50% of patients failing hypomethylating agents. This review aims to synthesize recent discoveries through an integrated network model and examine translation into precision therapeutic approaches. Methods: We reviewed breakthrough discoveries from the past three years, analyzing single-cell multi-omics technologies, epitranscriptomics, stem cell architecture analysis, and precision medicine approaches. We examined cell-type-specific splicing aberrations, distinct stem cell architectures, epitranscriptomic modifications, and microenvironmental alterations in MDS pathogenesis. Results: Four interconnected mechanisms drive MDS: genetic alterations (splicing factor mutations), aberrant stem cell architecture (CMP-pattern vs. GMP-pattern), epitranscriptomic dysregulation involving pseudouridine-modified tRNA-derived fragments, and microenvironmental changes. Splicing aberrations show cell-type specificity, with SF3B1 mutations preferentially affecting erythroid lineages. Stem cell architectures predict therapeutic responses, with CMP-pattern MDS achieving superior venetoclax response rates (>70%) versus GMP-pattern MDS (<30%). Epitranscriptomic alterations provide independent prognostic information, while microenvironmental changes mediate treatment resistance. Conclusions: These advances represent a paradigm shift toward personalized MDS medicine, moving from single-biomarker to comprehensive molecular profiling guiding multi-target strategies. While challenges remain in standardizing molecular profiling and developing clinical decision algorithms, this systems-level understanding provides a foundation for precision oncology implementation and overcoming current therapeutic limitations. Full article

Platelet-rich plasma (PRP) is widely applied in veterinary regenerative medicine due to its rich composition of growth factors that promote tissue repair. However, the direct pro-angiogenic function of canine PRP (cPRP) has not been thoroughly validated through controlled in vitro and in vivo experimentation. Human umbilical vein endothelial cells (HUVECs) were used to assess cell proliferation, migration, and tube formation after exposure to cPRP. In addition, a rabbit corneal micropocket assay was employed to evaluate in vivo angiogenic responses. Treatment with 20% cPRP significantly enhanced HUVEC proliferation and migration and induced robust tube formation. In the in vivo model, we observed dose-dependent neovascularization, with the earliest vascular sprouting seen on day 1 in the 40% group. Both models consistently demonstrated that cPRP stimulates vascular development in a concentration-dependent manner. This study provides novel evidence of cPRP’s capacity to induce neovascularization, supporting its therapeutic value for treating nonhealing wounds in dogs, especially in cases involving chronic inflammation, aging, or immune dysregulation. These findings offer a scientific foundation for the broader clinical application of cPRP in veterinary regenerative practice. Full article

Rising volumes of textile waste necessitate the development of more efficient recycling systems, with a primary focus on the optimization of sorting technologies. Near-infrared (NIR) spectroscopy is a state-of-the-art method for fiber identification; however, its accuracy in quantifying textile blends, particularly common polyester/cotton blend textiles, still requires refinement. This study explores the potential and limitations of NIR spectroscopy for quantifying cotton content in post-consumer textiles. A lab-scale NIR sorter and a handheld NIR spectrometer in complementary wavelength ranges were applied to a diverse range of post-consumer textile samples to test model accuracies. Results show that the commonly assumed 10% accuracy threshold in industrial sorting can be exceeded, especially when excluding textiles with <35% cotton content. Identifying and excluding the range of non-linearity significantly improved the model’s performance. The final models achieved an RMSEP of 6.6% and bias of −0.9% for the NIR sorter and an RMSEP of 3.1% and bias of −0.6% for the handheld NIR spectrometer. This study also assessed how textile characteristics—such as color, structure, product type, and alkaline treatment—affect spectral behavior and model accuracy, highlighting their importance for refining quantification when high-purity inputs are needed. By identifying current limitations and potential sources of errors, this study provides a foundation for improving NIR-based models. Full article

Background: Colorectal cancer (CRC) is a prevalent gastrointestinal malignancy, ranking third in incidence and second in cancer-related mortality. Despite therapeutic advances, challenges such as chemotherapy toxicity and drug resistance persist. Thus, there is an urgent need for novel CRC treatments. However, developing new drugs is time-consuming and resource-intensive. As a more efficient approach, drug repurposing offers a promising alternative for discovering new therapies. Methods: In this study, we screened 1068 small molecular compounds from an FDA-approved drug library in CRC cells. Menadione was selected for further study based on its activity profile. Mechanistic analysis included a cell death pathway PCR array, differential gene expression, enrichment, and network analysis. Gene expressions were validated by RT-qPCR. Results: We identified menadione as a potent anti-tumor drug. Menadione induced three programmed cell death (PCD) signaling pathways: necroptosis, apoptosis, and autophagy. Furthermore, we found that the anti-tumor effect induced by menadione in CRC cells was mediated through a key gene: MAPK8. Conclusions: By employing methods of cell biology, molecular biology, and bioinformatics, we conclude that menadione can induce multiple forms of PCD in CRC cells by activating MAPK8, providing a foundation for repurposing the “new use” of the “old drug” menadione in CRC treatment. Full article

Cryotherapy could stimulate immune responses and induce abscopal effects. A novel technique was developed for treating spinal bone tumors involving the use of frozen tumor-containing autologous bone grafts for anterior spinal reconstruction following total en-bloc spondylectomy, with the aim of activating cryoimmunity. This study focused on analyzing changes in the T-cell receptor (TCR) repertoire after surgery to evaluate T-cell diversity. Blood samples were collected pre- and post-operatively, with subsequent RNA extraction and immunosequencing. Compared to pre-surgery samples, the diversity and abundance of the Complementarity-Determining Region 3, regions of the TCR α and β chains decreased, suggesting that more selective clones may have emerged and influenced immune responses. Through TCR repertoire analysis, this study demonstrated that transplantation of frozen tumor-containing autologous bone impacted the immune system. This study is expected to provide a foundation for developing treatments that may enhance immune activation. Full article

This paper presents a novel approach employing localized annealing through Joule heating to enhance the performance of Thin-Film Piezoelectric-on-Silicon (TPoS) MEMS resonators that are crucial for applications in sensing, energy harvesting, frequency filtering, and timing control. Despite recent advancements, piezoelectric MEMS resonators still suffer from anchor-related energy losses and limited quality factors (Qs), posing significant challenges for high-performance applications. This study investigates interface modification to boost the quality factor (Q) and reduce the motional resistance, thus improving the electromechanical coupling coefficient and reducing insertion loss. To balance the trade-off between device miniaturization and performance, this work uniquely applies DC current-induced localized annealing to TPoS MEMS resonators, facilitating metal diffusion at the interface. This process results in the formation of platinum silicide, modifying the resonator’s stiffness and density, consequently enhancing the acoustic velocity and mitigating the side-supporting anchor-related energy dissipations. Experimental results demonstrate a Q-factor enhancement of over 300% (from 916 to 3632) and a reduction in insertion loss by more than 14 dB, underscoring the efficacy of this method for reducing anchor-related dissipations due to the highest annealing temperature at the anchors. The findings not only confirm the feasibility of Joule heating for interface modifications in MEMS resonators but also set a foundation for advancements of this post-fabrication thermal treatment technology. Full article

MOTS-c is a mitochondrial peptide that plays a crucial role in regulating energy metabolism, gene expression, and immune processes. However, current research primarily focuses on mammals like humans and mice, with no reports on avian MOTS-c. This study aimed to identify and characterize MOTS-c coding sequences across major poultry species through bioinformatics analysis and experimental validation. The alignment results showed high sequence similarity in the MOTS-c coding regions between avian and mammalian species. However, a single nucleotide deletion was identified in avian sequences at the position corresponding to the fourth amino acid residue of mammalian homologs, resulting in divergent downstream amino acid sequences. Despite this deletion, several residues were conserved across species. Phylogenetic analysis of mRNA sequences grouped pigeons with mammals, while protein sequence analysis revealed that poultry and mammals form separate branches, highlighting the divergence between avian and mammalian MOTS-c sequences. Tissue expression profiling demonstrated widespread distribution of chicken MOTS-c across multiple tissues, with the highest expression levels in the heart. Fasting significantly reduced heart MOTS-c expression, suggesting potential metabolic regulatory functions. Functional analysis of MOTS-c in primary hepatocytes revealed significant enrichment of the ribosome, oxidative phosphorylation, and key signaling pathways (PI3K-AKT and JAK-STAT) following 24 hours of treatment. Western blot validation confirmed MOTS-c-mediated activation of the AKT signaling pathway. This study represents the first comprehensive characterization of avian MOTS-c, providing critical insights into its evolutionary conservation and its potential functional roles in gene expression and cellular metabolism. Our findings establish a foundation for further investigation into the functions of mitochondrial-encoded peptides in avian species. Full article

Trust in Traditional Thai Medicine (TTM) among Thai people has been reduced due to a lack of objective standards and the susceptibility of the general population to false information. The emergence of generative artificial intelligence (Gen AI) has significantly impacted various industries, including traditional medicine. However, previous Gen AI models have primarily focused on prescription generation based on Traditional Chinese Medicine (TCM), leaving TTM unexplored. To address this gap, we propose a novel fast-learning fine-tuned language model fortified with TTM knowledge. We utilized textual data from two TTM textbooks, Wat Ratcha-orasaram Ratchaworawihan (WRO), and Tamra Osot Phra Narai (NR), to fine-tune Unsloth’s Gemma-2 with 9 billion parameters. We developed two specialized TTM tasks: treatment prediction (TrP) and herbal recipe generation (HRG). The TrP and HRG models achieved precision, recall, and F1 scores of 26.54%, 28.14%, and 24.00%, and 32.51%, 24.42%, and 24.84%, respectively. Performance evaluation against TCM-based generative models showed comparable precision, recall, and F1 results with a smaller knowledge corpus. We further addressed the challenges of utilizing Thai, a low-resource and linguistically complex language. Unlike English or Chinese, Thai lacks explicit sentence boundary markers and employs an abugida writing system without spaces between words, complicating text segmentation and generation. These characteristics pose significant difficulties for machine understanding and limit model accuracy. Despite these obstacles, our work establishes a foundation for further development of AI-assisted TTM applications and highlights both the opportunities and challenges in applying language models to traditional medicine knowledge systems in Thai language contexts. Full article

Traditional intensive agricultural system impedes ecological functions, such as nutrient cycling and biodiversity conservation, resulting in excessive nitrogen discharge, CH₄ emission, and ecosystem service losses. To enhance critical ecosystem services and mitigate environmental externalities in paddy fields, we developed a multi-objective agricultural system (MIA system), which combines two eco-functional units: paddy wetlands and Beitang (irrigation water collection pond). Pilot study results demonstrated that the MIA system enhanced biodiversity and inhibited pest outbreak, with only a marginal reduction in rice production compared with the control. Additionally, the paddy wetland effectively removed nitrogen, with removal rates of total nitrogen and dissolved inorganic nitrogen ranging from 0.06 to 0.65 g N m⁻² d⁻¹ and from 0.02 to 0.22 g N m⁻² d⁻¹, respectively. Continuous water flow in the paddy wetland reduced the CH₄ emission by 84.4% compared with the static water conditions. Furthermore, a simulation experiment indicated that tide flow was more effective in mitigating CH₄ emission, with a 68.3% reduction compared with the drying–wetting cycle treatment. The emergy evaluation demonstrated that the MIA system outperformed the ordinary paddy field when considering both critical ecosystem services and environmental externalities. The MIA system exhibited higher emergy self-sufficiency ratio, emergy yield ratio, and emergy sustainable index, along with a lower environmental load ratio. Additionally, the system required minimal transformation, thus a modest investment. By presenting the case of the MIA system, we provide a theoretical foundation for comprehensive management and assessment of agricultural ecosystems, highlighting its significant potential for widespread application. Full article

To elucidate the photosynthetic physiological mechanisms influencing alfalfa (Medicago sativa L.) yield and quality under varying planting densities, the cultivar ‘Zhongmu No.1’ was used as experimental material. The effects of different row spacing (R1, R2, R3) and seeding rate (S1, S2, S3, S4, S5) combinations on chlorophyll content (ChlM), nitrogen flavonol index (NFI), chlorophyll fluorescence parameters, forage quality, and hay yield were systematically analyzed. Results showed that alfalfa under R1S3 treatment achieved peak values for ChIM, NFI, EE, and hay yield, whereas R1S4 treatment yielded the highest Fv/Fm and CP content. Redundancy analysis further indicated that yield was most strongly associated with ChlM, NFI, Y (II), and qP. Y (II), and qP significantly influenced alfalfa forage quality, exerting negative effects on ADF and NDF, while demonstrating positive effects on CP and EE. In conclusion, narrow row spacing (15 cm) with moderate seeding rates (22.5–30 kg·hm⁻²) optimizes photosynthetic performance while concurrently enhancing both productivity and forage quality in alfalfa cultivated, establishing a theoretical foundation for photosynthetic regulation in high-quality and high-yield alfalfa cultivation. Full article

Equine piroplasmosis (EP) is a tick-borne disease caused by Theileria equi, Theileria haneyi and Babesia caballi. It affects equids, representing significant health and economic concerns for the equine industry. EP is endemic in Portugal, so developing and implementing preventive strategies is essential. Accessing veterinarians’ knowledge, attitudes and practices (KAP) through a survey is a suitable approach, and no such studies have been conducted in Portugal until now. A KAP survey was applied to 41 Portuguese equine vets, representing mainly the Alentejo region. The average knowledge score went from medium to high, correctly identifying the causative agents, transmission routes and clinical signs. Knowledge gaps mostly concerned the identification of T. haneyi as an agent, transplacental transmission, duration of infection and diagnostic methods. Reported practices were appropriate overall, including enhancing breeders’ awareness of the disease and its prevention. Diagnostic and treatment protocols were generally consistent with current recommendations; however, these protocols are not yet fully standardized. Our findings highlight key areas where increasing expertise is needed and could serve as a foundation for future evidence-based guidelines to improve EP control in Portugal. Full article