Search Results (2,084)

Litopenaeus vannamei, commonly known as the Pacific white shrimp, is one of the most economically significant species in global aquaculture, valued for its rapid growth and adaptability. However, the mechanisms regulating its growth, especially under high-density farming and environmental stress, remain poorly understood. Previous study predicted that LvSlc12A2 was involved in growth regulation. To further reveal the function of this gene in the growth regulation of the whiteleg shrimp, in this study, we explore its function using RT-qPCR, RNA interference, overexpression, and tissue in situ hybridization. RT-qPCR results showed that LvSlc12A2 was highly expressed in gills (about 62%), followed by the hepatopancreas, with the lowest expression in muscle (0.08%, compared to the gills). Myostatin (LvMstn) was mainly expressed in the heart, and molt-inhibiting hormone (LvMIH) in the ventral nerve. In situ hybridization of gill tissues using the mRNA of the gene as a probe revealed strong LvSlc12A2 signals in the gill stratum and epithelial cells. Overexpression of LvSlc12A2, significantly decreased the osmotic gene aquaporin (LvAqp), while knockdown increased its expression. Additionally, levels of growth-related inhibitory genes LvMstn and LvMIH increased significantly after LvSlc12A2 overexpression and were downregulated after its knockdown, suggesting LvSlc12A2 negatively regulates growth, possibly in synergy with LvMstn and LvMIH. These findings indicate LvSlc12A2 influences growth both by negative regulation and by modulating osmotic balance in gill tissues. Full article

Context and objective: Post-amputation pain (PAP) is an umbrella term that includes residual limb pain (RLP) and phantom limb pain (PLP), posing a significant challenge to recovery and quality of life after limb loss. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has gained interest for its potential to manage PAP, particularly in refractory cases. This narrative review explores the efficacy of ketamine for PAP and the emerging role of pharmacogenomics in guiding its use. Methods: A literature review of PubMed, Embase, and Cochrane databases was conducted, focusing on clinical trials, systematic reviews, and genetic influences on ketamine metabolism and response. Studies suggest that perioperative ketamine can reduce PAP severity and opioid use. However, outcomes vary, with some patients experiencing transient relief and others achieving prolonged benefit. Results: This variability may be linked to genetic differences in CYP2B6, CYP3A4/5, COMT Val158Met, SLC6A2, and KCNS1, which affect ketamine’s metabolism, efficacy and side effect profile. Understanding these pharmacogenomic factors could enable more personalized and effective ketamine therapy. Conclusion: Despite its promise, inconsistent dosing regimens and limited integration of genetic data hinder standardization. Further research into genotype-guided ketamine protocols may improve treatment outcomes and support precision analgesia in amputee care. Full article

Background: Paroxysmal dyskinesias (PDs) are rare, episodic movement disorders characterized by sudden and involuntary hyperkinetic motor events. In paediatric populations, their diagnosis is often complicated by clinical overlap with epilepsy and other neurological conditions. Genetic underpinnings have increasingly been recognized as key to understanding phenotypic heterogeneity and guiding treatment. Objectives: This systematic review aims to provide a comprehensive overview of paediatric PD, with a focus on genetic aetiologies, clinical features, subtype classification, and therapeutic approaches, including genotype–treatment correlations. Methods: We systematically reviewed the literature from 2014 to 2025 using PubMed. Inclusion criteria targeted paediatric patients (aged 0–18 years) with documented paroxysmal hyperkinetic movements and genetically confirmed or clinically suggestive PD. Data were extracted regarding demographics, dyskinesia subtypes, age at onset, genetic findings, and treatment efficacy. Gene categories were classified as PD-specific or pleiotropic based on functional and clinical features. Results: We included 112 studies encompassing 605 paediatric patients. The most common subtype was Paroxistic Kinesigenic Dyskinesia (PKD). Male sex was more frequently reported. The mean onset age was 5.99 years. A genetic diagnosis was confirmed in 505 patients (83.5%), involving 38 different genes. Among these, PRRT2 was the most frequently implicated gene, followed by SLC2A1 and ADCY5. Chromosomal abnormalities affecting the 16p11.2 region were identified in ten patients, including deletions and duplications. Among the 504 patients with confirmed monogenic variants, 390 (77.4%) had mutations in PD-specific genes, while 122 (24.2%) carried pleiotropic variants. Antiseizure drugs—particularly sodium channel blockers such as carbamazepine and oxcarbazepine—were the most frequently reported treatment, with complete efficacy documented in 59.7% of the studies describing their use. Conclusions: Paediatric PDs exhibit significant clinical and genetic heterogeneity. While PRRT2 remains the most common genetic aetiology, emerging pleiotropic genes highlight the need for comprehensive diagnostic strategies. Sodium channel blockers are effective in a subset of genetically defined PD, particularly PRRT2-positive cases. Patients with pathogenic variants in other genes, such as ADCY5 and SLC2A1, may benefit from specific therapies that can potentially change their clinical course and prognosis. These findings support genotype-driven management approaches and underscore the importance of genetic testing in paediatric movement disorders. Full article

Objective: This study aims to investigate the pharmacodynamic effects and underlying mechanisms of the Chinese herbal formula RuHaoDaShi (RHDS) granules against the influenza virus in experimental models. Methods: This study aims to employ network pharmacology to identify the active components of RHDS and its potential targets and mechanisms of action against H1N1. The molecular docking approach validated the interactions between the core targets and the RHDS compounds. In vitro, the antiviral activity of RHDS was assessed by therapeutic, prophylactic, and premixed administration to H1N1-infected A549 cells. An in vivo experiment was conducted using a mouse H1N1 pneumonia model. The model was treated with a dose of 1.04, 2.08, and 4.16 g/kg of RHDS, administered via gavage daily. The study’s objective was to evaluate the antiviral activity and mechanism of action of RHDS in mice. Mice were evaluated on day 6 by assessing survival, viral load (RT-qPCR), lung pathology (HE staining), inflammatory cytokines (ELISA, immunohistochemistry), and ferroptosis markers (WB, qPCR). Results: Network pharmacology identified 77 biologically active RHDS compounds (e.g., quercetin and kaempferol) and 32 core targets common to RHDS, H1N1, and ferroptosis. Molecular docking was used to verify a high affinity for binding between the core targets HIF-1α, MAPK3, and key RHDS compounds. In vitro studies demonstrated that RHDS exhibited protective properties against H1N1-infected cells, with the therapeutic delivery method proving the most efficacious. In vivo studies have shown that RHDS reduces mortality, lung index, and viral load in mice while attenuating histopathological damage. The study demonstrated a reduction in the release of inflammatory cytokines, including IL-6, IFN-γ, and IL-17A, and decreased expression levels of MPO and F4/80 proteins in lung tissue. Mechanistically, the administration of RHDS resulted in the up-regulation of the expression levels of GPX4, SLC7A11, and Nrf2 proteins while concomitantly inhibiting the expression of HIF-1α, COX2, and ACSL4. These findings confirm the modulatory effect of RHDS on the GPX4/SLC7A11/Nrf2 pathway. Conclusions: RHDS demonstrated a protective effect against H1N1-induced cytopathy in vitro and was effective in attenuating H1N1-induced pneumonia in murine models. The study suggests that RHDS has antiviral potential to treat H1N1 viral pneumonia by modulating inflammatory cytokines and the GPX4/SLC7A11/Nrf2 pathway. Full article

Air moving-target detection is crucial for national defense, civil aviation, and airspace supervision. Spaceborne synthetic aperture radar (SAR) provides high-resolution, continuous observations for this task, but faces challenges including target attitude variation-induced weak signals and Doppler defocusing from targets’ high-speed motion, which hinder target-background separation. To address this, we propose a novel method combining sub-aperture segmentation with GoDec+ low-rank decomposition to enhance signal-to-noise ratio and suppress defocusing. Critically, ADS-B flight data is integrated as ground truth for spatio-temporal validation. Experiments using Sentinel-1 SM mode SLC imagery across farmland, forest, and mountainous regions confirm the method’s effectiveness and robustness in real airspace scenarios. Full article

Zinc is an essential trace element involved in critical physiological functions such as gene expression, immune regulation, and cellular proliferation. This review explores the link between zinc homeostasis and cancer, with a specific focus on LIV-1 zinc transporters and their potential relevance to cancer research and treatment priorities in Saudi Arabia, as informed by global data. Zinc homeostasis is maintained by two major transporter families: ZIP (SLC39A) and ZnT (SLC30A). The dysregulation of specific ZIP transporters, particularly ZIP4, ZIP7, ZIP6, and ZIP10, has been implicated in cancer progression. Bioinformatic analyses revealed the significant overexpression of ZIP4, ZIP7, and ZIP6 in breast cancer and ZIP4 in colorectal cancer, which are the most common cancers among Saudi women and men, respectively. Notably, ZIP4 and ZIP7 upregulation correlated with poorer clinical outcomes, whereas ZIP6 was positively associated with survival in breast cancer. These findings underscore the potential of zinc transporters as prognostic biomarkers and therapeutic targets. Despite the substantial global evidence, research on zinc transporters in the Saudi population remains limited. Considering the Kingdom’s rising cancer burden and unique genetic, environmental, and dietary factors, understanding zinc metabolism in this context is important. Targeted research may support precision medicine strategies and improve outcomes in line with Saudi Arabia’s healthcare transformation goals. Full article

Background: Monocarboxylate-transporter-8-(MCT8) deficiency, or Allan–Herndon–Dudley syndrome (AHDS), is a rare X-linked disorder caused by pathogenic variants in the SLC16A2 gene, leading to impaired transport of thyroid hormones, primarily T3 and T4, across cell membranes. The resulting central hypothyroidism and peripheral hyperthyroidism cause neurodevelopmental impairment and thyrotoxicosis. Despite the availability of therapy options, e.g., with triiodothyroacetic acid (TRIAC), diagnosis is often delayed, partly due to normal TSH levels or incomplete genetic panels. MCT8 deficiency is not yet included in newborn-screening programs worldwide. Case Description: We present a case of an infant genetically diagnosed with MCT8 deficiency at 5 months of age after presenting with muscular hypotonia, lack of head control, and developmental delay. Thyroid function testing revealed a normal TSH, low free T4, and significantly elevated free T3 and free T3/T4 ratio. Treatment with TRIAC (Emcitate^®) was initiated promptly, with close drug monitoring. Despite persistent motor deficits and dystonia, some developmental progress was observed, as well as reduction in hyperthyroidism. Discussion/Conclusions: This case underscores the importance of early free T3 and fT3/fT4 ratio testing in infants with unexplained developmental delay. Broader inclusion of SLC16A2 in genetic panels and consideration of newborn screening could improve early diagnosis and outcomes in this rare but treatable condition. Full article

Meat quality is influenced by genetic, nutritional, and microbial factors, with increasing attention on the role of gut-derived metabolites. In this study, we conducted untargeted metabolomics of 10 gut tract sites and RNA sequencing (RNA-seq) of longissimus dorsi muscles in Meigu goats and Liangshan black sheep raised under standardized conditions. Results showed that goat muscle contained significantly higher levels of essential amino acids (e.g., methionine) and specific fatty acids (e.g., C18:3_N6, C20:4_N6), suggesting improved nutritional quality. Transcriptomic analysis identified 3133 differentially expressed genes (DEGs), among which ADCY1 and SLC38A4 were upregulated in goats and strongly associated with meat traits. Using integrative correlation analysis, we uncovered 17 genes and 19 gut metabolites that were significantly correlated with more than eight meat quality parameters across multiple gut sites. Notably, these metabolites included bioactive compounds such as L-tyrosine ethyl ester and pelargonidin 3-O-glucoside, while genes were enriched in pathways related to amino acid transport, cAMP signaling, and muscle development. Together, these findings highlight a potential gut–muscle axis involving metabolite-mediated modulation of muscle gene expression, contributing to breed-specific differences in meat composition and quality. This study provides a valuable framework for improving ruminant meat quality through integrative multi-omics analysis. Full article

SLC5A8 is a protein coded by the SLC5A8 gene, and has been proposed as a tumor suppressor and iodide transporter. Its expression is reduced in papillary thyroid carcinoma (PTC), yet the mechanisms underlying this phenomenon are largely unknown. We hypothesized that SLC5A8 expression in PTC is reduced by microRNAs and can be modulated by their inhibition. We used real-time PCR to analyze the expression of SLC5A8 and the microRNAs of interest in a set of 49 PTC/normal tissue pairs. We used an in silico approach to identify microRNAs upregulated in PTC and putatively binding to the SLC5A8 transcript. Luciferase assays were performed to confirm the direct binding of synthetic microRNAs to the 3′UTR of SLC5A8. Subsequently, using mir-expressing plasmids and microRNA sponges, including a microRNA sponge designed to simultaneously inhibit three selected microRNAs, we checked the impact of the modulation of microRNAs on endogenous SLC5A8. Finally, we investigated if modulation of SLC5A8 induces changes in transcriptomes. We confirmed the downregulation of SLC5A8 in PTC. In silico analysis revealed microRNAs potentially targeting SLC5A8. Luciferase assay confirmed direct binding between the 3′UTR of SLC5A8 and miR-181a-5p, miR-182-5p, and miR-494-3p. MiR-181a-5p and miR-182-5p were upregulated in PTC. In HEK293 cell lines, transfection with mir-181a- and mir-182-expressing plasmids decreased endogenous SLC5A8 mRNA, while silencing of miR-181a-5p, miR-182-5p, miR-494-3p, and all three microRNAs simultaneously increased SLC5A8 expression; however, only simultaneous inhibition was able to induce changes visible for SLC5A8 protein. Changes in SLC5A8 expression did not alter the whole transcriptome significantly. This study shows microRNA-dependent regulation of SLC5A8 expression and underlines the potential effectiveness of simultaneous inhibition of a few microRNAs to derepress their common target. Full article

Background and Objectives: Hypocitraturia is a major risk factor for calcium-containing kidney stone disease. Citrate inhibits stone formation by binding calcium in the urine. The SLC13A2 gene encodes the sodium-dependent dicarboxylate cotransporter 1 (NaDC1), a membrane transport protein that facilitates citrate reabsorption in the proximal renal tubules. Variants in this gene, such as rs11568476 (V477M), have been shown to significantly impair transporter activity. This study aimed to investigate the presence of the rs11568476 polymorphism in SLC13A2 and its association with hypocitraturia in Turkish patients with calcium-containing kidney stones. To our knowledge, this is the first genetic study evaluating this polymorphism in a Turkish cohort. Materials and Methods: This prospective cross-sectional study included 90 patients diagnosed with calcium-containing kidney stones at Düzce University Faculty of Medicine, Department of Urology. Based on 24 h urinary citrate levels, patients were divided into two groups: normocitraturic (n = 38) and hypocitraturic (n = 52). Blood and 24 h urine samples were analyzed for biochemical parameters. The rs11568476 polymorphism in SLC13A2 was analyzed using Real-Time PCR. Results: There were no significant differences between the two groups in terms of age, gender, and most biochemical parameters. Serum uric acid levels were significantly higher in the hypocitraturic group (p = 0.002), whereas family history of stone disease was more prevalent in the normocitraturic group (p = 0.024). Genetic analysis revealed no polymorphism in the rs11568476 region; all patients exhibited the homozygous wild-type genotype (GG). Conclusions: No association was observed between the rs11568476 polymorphism and hypocitraturia in this cohort. The absence of the polymorphism suggests that this variant may be rare or absent in the Turkish population. These findings highlight the importance of investigating additional genetic and environmental contributors to hypocitraturia and nephrolithiasis through larger, multicenter studies. Full article

As the laying cycle is prolonged, the egg albumen quality exhibits a declining trend. A Haugh unit (HU) is a standard measure of the albumen quality, which reflects viscosity and freshness. During the late laying period, the HU not only decreased significantly, but also exhibited greater variability among individuals. The magnum, as the primary site of albumen synthesis, plays a central role in this process; however, the mechanisms by which it regulates the albumen quality remain unclear. To address this, we obtained genomic and transcriptomic data from 254 individuals, along with single-cell RNA sequencing (scRNA-seq) data of the magnum tissue. Genome-wide association studies (GWAS) across five laying stages (66, 72, 80, 90, and 100 weeks of age) identified 77 HU-associated single-nucleotide polymorphisms (SNPs). Expression quantitative trait locus (eQTL) mapping linked these variants to the expression of 12 genes in magnum tissue. In addition, transcriptomic analysis using linear regression and random forest models identified 259 genes that significantly correlated with the HU. Single-cell RNA sequencing further revealed two key cell types, plasma cells and a subset of epithelial cells, marked by ADAMTSL1 and OVAL, which are functionally relevant to the HU. Through integrated Transcriptome-Wide Association Study (TWAS) and Summary-data-based Mendelian Randomization (SMR) analyses, we identified four robust regulators of the albumen quality: CISD1, NQO2, SLC22A23, and CMTM6. These genes are functionally involved in mitochondrial function, antioxidant defense, and membrane transport. Overall, our findings uncovered the genetic and cellular mechanisms underlying age-related decline in the albumen quality and identified potential targets for improving the egg quality in aging flocks. Full article

Tumor-initiating cells (TICs) constitute a subpopulation of cancer cells with stem-like properties contributing to tumorigenesis, progression, recurrence, and therapeutic resistance. Despite their biological importance, their molecular signatures that distinguish them from non-TICs remain incompletely characterized. This study aimed to comprehensively analyze transcriptomic differences between TICs and non-TICs, identify TIC-specific gene expression patterns, and construct a machine learning-based classifier that could accurately predict TIC status. RNA sequencing data were obtained from four human cell lines representing TIC (TS10 and TS32) and non-TIC (32A and Epi). Transcriptomic profiles were analyzed via principal component, hierarchical clustering, and differential expression analysis. Gene-Ontology and Kyoto-Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted for functional interpretation. A logistic-regression model was trained on differentially expressed genes to predict TIC status. Model performance was validated using synthetic data and external projection. TICs exhibited distinct transcriptomic signatures, including enrichment of non-coding RNAs (e.g., MIR4737 and SNORD19) and selective upregulation of metabolic transporters (e.g., SLC25A1, SLC16A1, and FASN). Functional pathway analysis revealed TIC-specific activation of oxidative phosphorylation, PI3K-Akt signaling, and ribosome-related processes. The logistic-regression model achieved perfect classification (area under the curve of 1.00), and its key features indicated metabolic and translational reprogramming unique to TICs. Transcriptomic state-space embedding analysis suggested reversible transitions between TIC and non-TIC states driven by transcriptional and epigenetic regulators. This study reveals a unique transcriptomic landscape defining TICs and establishes a highly accurate machine learning-based TIC classifier. These findings enhance our understanding of TIC biology and show promising strategies for TIC-targeted diagnostics and therapeutic interventions. Full article

Background/Objectives: Genetic variation has been thought to alter the human dietary requirement for choline and subsequent circulating levels of its metabolites betaine and dimethylglycine (DMG). The aim of this genome-wide association study (GWAS) was to identify single nucleotide polymorphisms (SNPs) associated with serum choline, betaine, and dimethylglycine (DMG) as well as choline-to-betaine and betaine-to-DMG ratios. Methods: Data from the Collaborative Study of Genes, Nutrients and Metabolites (CSGNM; n = 2402) were used to model individual associations of choline, betaine, and DMG circulating metabolites and their ratios with 680,975 SNPs, using linear regression. Models were unadjusted (model 1), adjusted for age and sex (model 2), and further adjusted for selected principal components (model 3) and B₁₂, B₉, B₆, and holotranscobalamin (model 4). Statistical significance was set at p < 5.0 × 10⁻⁵. Affected SNPs in the dbSNP (database of Single Nucleotide Polymorphisms) were then identified. Results: GWAS revealed both intuitive and novel results, including the recently described SLC25A48, several intronic variants in the gene encoding LYPLAL1, and a pair of SNPs present in the intronic region of PID1 related to serum choline. SNPs related to betaine and DMG included SLCA12, BHMT, DMGDH, and additional SLC family transporters that require further validation. While exploratory, GWAS of the choline-to-betaine and betaine-to-DMG ratios revealed common targets with direct links to choline and one-carbon metabolism. Conclusions: These results suggest that metabolic handling of choline has genetic determinants not formerly recognized in the scientific literature. Replication is needed in larger cohorts due to low statistical power. Full article

Ferroptosis is an iron-dependent form of regulated cell death marked by lipid peroxidation in polyunsaturated phospholipids. In head and neck cancer (HNC), where resistance to chemotherapy and immunotherapy is common, ferroptosis offers a mechanistically distinct strategy to overcome therapeutic failure. However, cancer cells often evade ferroptosis via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of antioxidant and iron-regulatory genes. HNC remains therapeutically challenging due to therapy resistance driven by redox adaptation. This review highlights the ferroptosis pathway—a form of regulated necrosis driven by iron and lipid peroxidation—and its regulation by Nrf2, a master antioxidant transcription factor. We detail how Nrf2 contributes to ferroptosis evasion in HNC and summarize emerging preclinical studies targeting this axis. The review aims to synthesize molecular insights and propose therapeutic perspectives for overcoming resistance in HNC by modulating Nrf2–ferroptosis signaling. We conducted a structured narrative review of the literature using PubMed databases. Relevant studies from 2015 to 2025 focusing on ferroptosis, Nrf2 signaling, and head and neck cancer were selected based on their experimental design, novelty, and relevance to clinical resistance mechanisms. In HNC, Nrf2 mediates resistance through transcriptional upregulation of GPX4 and SLC7A11, epigenetic stabilization by PRMT4 and ALKBH5, and activation by FGF5 and platelet-derived extracellular vesicles. Epstein–Barr virus (EBV) infection also enhances Nrf2 signaling in nasopharyngeal carcinoma. More recently, loss-of-function KEAP1 mutations have been linked to persistent Nrf2 activation and upregulation of NQO1, which confer resistance to both ferroptosis and immune checkpoint therapy. Targeting NQO1 in KEAP1-deficient models restores ferroptosis and reactivates antitumor immunity. Additionally, the natural alkaloid trigonelline has shown promise in reversing Nrf2-mediated ferroptosis resistance in cisplatin-refractory tumors. Pharmacologic agents such as auranofin, fucoxanthin, carnosic acid, and disulfiram/copper complexes have demonstrated efficacy in sensitizing HNC to ferroptosis by disrupting the Nrf2 axis. This review summarizes emerging mechanisms of ferroptosis evasion and highlights therapeutic strategies targeting the Nrf2–ferroptosis network. Integrating ferroptosis inducers with immune and chemotherapeutic approaches may provide new opportunities for overcoming resistance in head and neck malignancies. Full article

The mammalian amygdala is located in the temporal lobe of the telencephalon and plays a key role in limbic processing. Recently, our group proposed a radial morphological model to understand the glutamatergic (pallial) part of this nuclear complex in terms of separate progenitor domains. This model explains the amygdala region as consisting of several adjacent developmental radial progenitor units, disposing their distinct periventricular, intermediate, and superficial strata from the ventricle to the pial surface. It was expected that cell populations belonging to specific progenitor domains would present greater molecular similarity to each other than to neighboring developmental units. In this work, we aim to corroborate the existence of several radial domains in the pallial amygdala at the transcriptomic level. snRNAseq experiments in the amygdala of adult mice of both sexes indicated that at low resolution, the whole pallial amygdala was found to divide into two super-radial domains distinguished by differential expression of Slc17a6 and Slc17a7; the former partly imitates molecularly the subpallial (output) amygdalar regions, whereas the rest of the pallial amygdala is molecularly more akin to the surrounding cortical areas. In addition, our snRNAseq transcriptomic analysis fully supports the postulated amygdalar radial model of four main radial domains. Full article