ABSTRACT Silica nanoparticles (SiO 2 NPs) are widely used in biomedical and industrial applications, raising concerns about chronic exposure effects. This study investigated the impact of 90‐day oral SiO 2 NP exposure on male reproductive function in Wistar rats ( n = 6). In accordance with OECD 408 guidelines and our 14‐day range‐finding study, doses of 500, 1000, and 2000 mg/kg were selected, with 2000 mg/kg identified as the highest nontoxic level for sub‐chronic exposure, and reproductive endpoints including hormone levels, sperm quality, and testicular histopathology were subsequently evaluated. Exposure resulted in significant dose‐dependent reductions in body weight, food intake, reproductive organ weights, and serum hormone levels such as testosterone (T), follicle‐stimulating hormone (FSH), and luteinizing hormone (LH) ( p < 0.001), accompanied by histopathological damage to testicular tissue. Sperm count, vitality, motility, and morphology were significantly and dose‐dependently impaired. Enzymatic activities of testicular biomarkers‐including acid phosphatase (ACP), glucose‐6‐phosphate dehydrogenase (G6PD), γ‐glutamyl transferase (γ‐GT), and succinate dehydrogenase (SDH) were significantly decreased (< 0.001), suggesting metabolic dysfunction. Real‐time PCR analyses revealed downregulation of SF‐1 and associated steroidogenic genes (HSD3B1, HSD17B10, StAR), which was associated with altered testosterone biosynthesis. The observed SF‐1 downregulation was associated with altered steroidogenic regulation, possibly mediated through oxidative and endocrine stress pathways. This study highlights the importance of assessing the long‐term safety of SiO 2 NPs and their impact on reproductive health, particularly in the context of SF‐1‐mediated mechanisms.

Genetic disorders like sickle cell disease (SCD), Thalassemia, and Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency significantly impact social, health, financial, and healthcare systems, affecting 2%-5% of live births, 30% of pediatric hospitalisations, and 50% of juvenile deaths. Premarital carrier screening (PMCS) is a critical preventive measure, yet it remains unexplored in Ghana's Ahafo Region. This study examined young adults' knowledge and factors influencing willingness or unwillingness to undergo PMCS for genetic blood disorders. A cross-sectional study was conducted among 460 young adults (18-35 years) in health facilities in the Ahafo Region, Ghana, from January to March 2024. Data was collected using a validated and translated questionnaire to capture socio-demographic characteristics, knowledge of genetic disorders, and factors influencing willingness to undergo PMCS. Data analysis was performed using Stata v14, with statistical significance set at p < 0.05. Chi-square tests were used to assess associations between socio-demographic factors and willingness to undergo PMCS. Logistic regression analysis was conducted to identify predictors of willingness, presenting results as odds ratios (OR) with corresponding p-values. Among the 460 respondents, most (n = 294; 63.9%) knew their SCD status, but fewer were aware of their G6PD (n = 418; 90.9%) and Thalassemia (n = 441; 95.9%) statuses. A significant number had not tested for SCD (n = 303; 65.9%), G6PD (n = 421; 91.5%), or Thalassemia (n = 446; 97.0%). Among the 460 respondents, 88.5% expressed willingness to undergo PMCS. A chi-square test revealed that sex (χ² = 11.481, p = 0.0032)., education level (χ² = 8.428, p = 0.0379), and parental consanguinity (χ² = 14.336, p = 0.0136) were significantly associated with willingness to undergo PMCS. Logistic regression analysis revealed higher willingness among females [OR = 4.3, p = 0.002], cohabiting individuals [OR = 0.3, p = 0.021], married individuals [OR = 0.1, p = 0.001], self-employed [OR = 0.2, p = 0.047], unemployed [OR = 0.2, p = 0.037], and those informed through school subjects [OR = 0.2, p = 0.036]. Despite low awareness of genetic disorders, willingness to undergo PMCS is high among young adults in the Ahafo Region, highlighting the need for integrated, culturally tailored public health strategies, particularly through school-based education to improve uptake and reduce the burden of hereditary conditions.

Loss of TFAM accelerates pentose phosphate pathway by unleashing G6PD oligomerization to drive hepatocarcinogenesis.

Under the dual hit: genetic and phenotypic analysis of a Han family with severe adolescent cirrhosis from the convergence of Wilson's disease and favism.

Invasion and development of Plasmodium falciparum in erythroblasts of humans carrying G6PD viangchan.

Abnormal energy metabolism patterns are common characteristics of various tumor cells, including hepatocellular carcinoma cells (HCC). HCC undergo metabolic reprogramming, upregulating the tricarboxylic acid (TCA) cycle and mitochondrial respiration to provide energy. Based on this, we constructed a novel reactive oxygen species (ROS)- and ultrasound-responsive nanodroplet (named sGTND), which were loaded with glucose-6-phosphate dehydrogenase (G6PD) siRNA and modified with glycyrrhetinic acid (GA) via GTC polymer. These sGTNDs have a particle size of approximately 300nm, exhibit excellent biocompatibility and contrast-enhanced ultrasound imaging. By recognizing GA receptors, sGTNDs can be specifically targeted and enriched within HCC. Under the combined effect of ultrasound-targeted microbubble destruction (UTMD), sGTNDs release GA to activate the nuclear factor erythroid 2-related factor 2 (NRF2) while simultaneously releasing siRNA to inhibit G6PD. This dual action synergistically inhibits the TCA cycle, resulting in an antitumor efficacy of up to 95.1%, which is significantly higher than that observed in the control groups. Thus, the combination of sGTND and UTMD can effectively inhibit the TCA cycle through NRF2 activation and G6PD inhibition, which represents a promising therapeutic approach for HCC.

Synergistic regulation of SLC7A11 and glucose-6-phosphate dehydrogenase in redox homeostasis governs decidualization: a mechanistic insight into adenomyosis-related infertility.

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency, prevalent in malaria-endemic regions, has been associated with a reduced risk of severe malaria due to impaired parasite growth in deficient erythrocytes. The G6PD gene, located on the X chromosome, harbours various mutations associated with differing enzyme activity levels. This study investigates the prevalence of G6PD deficiency variants and their impact on parasite density and haemoglobin levels among malaria-positive patients in Awka, Anambra State, Nigeria.Materials and MethodsBlood samples were collected from 100 malaria positive participants; 64 participants with complete genotyping and clinical data were included in the analysis and screened for the A376G and G202A variants using PCR and Sanger sequencing.Results Molecular analysis indicated that the B variant (normal) was predominant, with 83% of the participants possessing this variant. None of the participants tested had the A- variant, associated with G6PD defciency, suggesting no evidence of the G202A (A−) variant in this hospital-based sample. The B variant and the A+ variant showed no significant impact on the haemoglobin and parasitaemia levels of the study participants. Conclusions The findings support the absence of the G202A (A−) variant in this cohort and show no detectable differences in parasitaemia or haemoglobin between A+ and B genotypes. Broader genotyping and/or G6PD enzyme activity testing in community representative samples is recommended before drawing population-level conclusions or informing treatment policy.

Objective: To investigate the correlation between the expression of glucose-6-phosphate dehydrogenase (G6PD) and the clinicopathological characteristics, prognosis and immune cell infiltration of hepatocellular carcinoma (HCC). Methods: The expression of G6PD in liver cancer tissues and normal tissues is extracted from TCGA and GEO databases, validated by immunohistochemistry, and the correlation between G6PD expression and clinical features is analyzed. The clinical significance of G6PD in liver cancer is assessed by Kaplan-Meier, Cox regression, and prognostic line graph models. Functional enrichment analysis is performed by protein-protein interaction (PPI) network, GO/KEGG, GSEA and for G6PD-associated differentially expressed genes (DEGs). TIMER and ssGSEA packages are used to assess the correlation between expression and the level of immune cell infiltration. Results: Analysis of TCGA and GEO datasets revealed that G6PD expression is significantly upregulated in hepatocellular carcinoma tissues (P &lt; 0.001). G6PD expression is associated with histological grade, pathological stage, T-stage, vascular infiltration, and AFP level (P &lt; 0.05); HCC patients in the low G6PD expression group had longer overall survival and better prognosis compared with the high G6PD expression group (P &lt; 0.05). The level of G6PD expression affects the levels of macrophages, dendritic cells, B cells, and follicular helper T cells in the tumor microenvironment. Conclusion: High expression of G6PD is a potential biomarker for poor prognosis of hepatocellular carcinoma, and G6PD may be a target for immunotherapy of HCC.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is traditionally recognized as a risk factor for drug- or infection-induced hemolytic anemia. Emerging evidence implicates potential roles of G6PD in neurodevelopment, yet its association with rare neurological disorders remains underexplored in population-based genetic studies, especially within the Chinese population. We conducted a retrospective case-control study utilizing whole-exome sequencing (WES) data from a Chinese cohort. Six most prevalent pathogenic G6PD variants in China were screended in children with rare neurological disorders (n = 211) and in controls without neurological involvement (n = 202). Genotype and carrier frequency comparisons were performed. Stratified analyses were performed based on diagnostic certainty and the presence of de novo mutations. Multivariable logistic regression was employed to calculate sex-adjusted odds ratios (ORs) to control for potential sex-related confounding. After adjusting for sex, the overall carrier rate of pathogenic G6PD variants was significantly higher in patients with neurological disorders than in controls (adjusted OR = 2.44, 95% CI: 1.18-5.06, p = 0.014). Further comparisons across specific groups revealed distinct patterns: affected male patients had a higher carrier rate than their own unaffected fathers (OR = 2.30, 95% CI: 1.08-4.91, p = 0.043), and mothers of case patients showed a higher carrier rate than mothers of controls (OR = 2.03, 95% CI: 1.09-3.78, p = 0.030). The variants NM_001042351.3: c.1376G>T (G6PD Canton) and NM_001042351.3:c.1388G>A (G6PD Kaiping) were the most prevalent across all groups. This population-based genetic analysis provides preliminary evidence that G6PD deficiency may be a underrecognized genetic risk factor for rare neurological disorders in Chinese children. The findings suggest a potential maternal genetic contribution and indicate that the phenotypic spectrum of G6PD deficiency may extend beyond hematological manifestations to include neurodevelopmental vulnerability. Important limitations include the lack of functional validation and the use of a clinical control group. Further prospective studies incorporating G6PD enzyme activity assessment and functional investigations are warranted to elucidate the underlying mechanisms.

The function and molecular mechanism of HIF-1α interacted with p-STAT3 in promoting G6PD overexpression in chronic myelogenous leukemia cells.

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy characterized by metabolic reprogramming that supports tumour growth and survival. This study identifies farnesyl diphosphate synthase (FDPs), a key enzyme in the mevalonate pathway, as a critical regulator of HCC proliferation and apoptosis. We applied bioinformatics analysis through TCGA and GSE database to identify the expression of FDPs within HCC patients. Then, mechanistic studies were conducted including Western blots, apoptosis assay, RT-qPCR, rescue assay, RNA-sequencing, invivo study to prove the role of FDPs in regulating HCC progression. FDPs was found to be significantly upregulated in HCC tissues, and its down-regulation promotes tumour cell apoptosis while inhibiting tumour cell proliferation invitro and invivo. Mechanistically, we identified FDPs regulate glucose-6-phosphate dehydrogenase (G6PD) by RNA sequencing, bioinformatics prediction, and rescue experiments, indicating its involvement in glycolysis regulation in tumour cells. The identification of this FDPs-G6PD axis suggests a novel metabolic pathway contributing to HCC development. In summary, this study highlights FDPs play an essential oncogenic role in HCC, linking it to metabolic reprogramming and tumour survival. These findings establish FDPs as a promising therapeutic target, offering a foundation for further exploration of its regulatory mechanisms and potential clinical applications.

Effectiveness and safety of 7-day high-dose primaquine and single-dose tafenoquine versus 14-day low-dose primaquine in patients with Plasmodium vivax malaria (EFFORT): a multicentre, open-label, randomised, controlled, superiority trial.

Chilling has been recognized as a stress factor adversely impacting plant growth and productivity. Even a slight decrease in temperature may significantly reduce crop yield. Recently, biostimulants have emerged as a new tool for enhancing the chilling tolerance of cold-sensitive plants. The early stages of cucumber growth often occur under suboptimal temperatures, which motivated the aim of the current study to assess the effect of a protein hydrolysate (PH) on the physiological performance of young cucumber plants subjected to chilling stress. The results showed that low temperatures caused severe chilling stress by inducing changes in growth, photosynthesis, and nitrogen assimilation. These adverse effects were mitigated when the PH was supplied. The ameliorating effect could be due to a remedial influence on photosynthetic pigment content, facilitating light harvesting and energy utilization. The potential impact of the PH treatment on the redox balance was demonstrated by the activation of the G6PD gene. The possible effect of the biostimulant on nitrate assimilation was tested by measuring nitrate reductase activity, which improved after application of the biostimulant. Moreover, the activity of phenylalanine ammonia-lyase (PAL) in PH-supplied plants was also increased, further confirming the enhanced protective capacity of the plants. All obtained results indicate the beneficial effect of PH application on cucumber plants and their chilling resilience.

Development and implementation of droplet digital PCR assays for accurate quantification of Plasmodium vivax parasitemia and G6PD viangchan genotyping.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in the Middle East and is a recognized risk factor for neonatal hyperbilirubinemia. However, the clinical impact of specific G6PD gene variants on hyperbilirubinemia severity remains unclear. This study aimed to determine the prevalence of G6PD gene variants among neonates at Johns Hopkins Aramco Healthcare and to evaluate their association with hyperbilirubinemia severity and phototherapy requirements. We conducted a retrospective cohort study of neonates diagnosed with G6PD deficiency between January 2021 and December 2023. Demographic, clinical, laboratory, and genetic data were collected from electronic medical records. G6PD variants were identified using newborn DNA screening. Associations with phototherapy requirement were assessed using chi-square and Mann-Whitney U tests. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of phototherapy. Among 5,375 neonatal admissions, 572 (10.6%) neonates were diagnosed with G6PD deficiency, with a male predominance (66.6%). The c.563C>T (Mediterranean) variant was the most prevalent (93.5%). Phototherapy was required in 193 neonates (33.7%). In multivariate analysis, female sex was independently protective against phototherapy (adjusted odds ratio (AOR) = 0.239; p = 0.003), while a positive Coombs test (AOR = 8.668; p < 0.001) and the presence of two mutant G6PD gene copies (AOR = 3.890; p = 0.007) were significant independent predictors of phototherapy requirement. No significant association was observed between specific G6PD variants and the need for phototherapy. G6PD deficiency was common in this cohort and was mainly associated with the c.563C>T mutation. A positive Coombs test and multiple gene copies were independent predictors of phototherapy, whereas specific G6PD variants were not associated with hyperbilirubinemia severity. These findings support the importance of early G6PD screening and vigilant monitoring to prevent severe neonatal hyperbilirubinemia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency exhibits high prevalence in malaria-endemic regions and areas along the historic Maritime Silk Road. This study investigated the burden and genetic architecture of G6PD deficiency in Nanning, the ethnically diverse capital of Guangxi in southern China, where Southeast Asian gene flow has shaped population genetics. We screened 14 403 individuals for G6PD activity at The First Affiliated Hospital of Guangxi Medical University, defining deficiency as activity < 60% of adjusted male median (AMM = 2045 U/L). Among 2513 deficient cases (prevalence: 17.45%), frequency was significantly higher in males (63.75%) vs. females (36.25%; p < 0.001) and Han Chinese (60.92%) vs. Zhuang (39.08%; p = 0.925). Multiplex melting curve analysis (MMCA) of 2513 enzyme-deficient samples identified pathogenic mutations in 1161 cases, revealing 13 distinct variants. The predominant mutations were: c.1388G>A (39.53%; 459/1161), c.1376G>T (24.81%; 288/1161), and c.95A>G (12.40%; 144/1161). Mutation c.871G>A exhibited male bias (p < 0.001), while c.95A>G was Zhuang-enriched (p < 0.001). Sanger sequencing of MMCA-negative cases identified two rare pathogenic variants (c.406C>T, c.196T>A). Our findings establish Nanning as a region of exceptionally high G6PD deficiency prevalence and delineate a distinct mutation profile with sex- and ethnicity-linked distributions. These results provide critical insights for designing precision screening programs and public health strategies tailored to this genetically diverse population.

Viruses frequently reprogram host metabolism to support their replication. The pentose phosphate pathway (PPP), a key regulator of nucleotide synthesis and redox balance, is often targeted during infection. While PPP activation is well-known proviral mechanism in vertebrates, how this process occurs in invertebrate hosts remains unclear. Here, using the white spot syndrome virus (WSSV) and its penaeid shrimp host as a model, we identify a previously unrecognized viral strategy that directly reprograms the PPP through host-viral protein interaction. WSSV infection strongly induced the expression of key PPP enzymes, including glucose-6-phosphate dehydrogenase (G6PD) and transketolase-like 2 (TKTL2), and enhanced TKTL2 enzymatic activity. This activation increased the production of nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate (R5P), two critical PPP metabolites. Functional assays confirmed that the PPP is essential for efficient WSSV replication, as knockdown or pharmacological inhibition of G6PD or TKTL2 significantly attenuated viral load and improved host survival. Mechanistically, the viral immediate-early protein IE1 was found to directly bind to the C-terminal region of TKTL2 (TKTL2-C1, residues 500-555), and enhance its enzymatic activity. This interaction promoted PPP flux, boosted NADPH and R5P biosynthesis, and suppressed reactive oxygen species (ROS) accumulation. Supplementation with NADPH, R5P, or a ROS scavenger restored viral replication defects caused by IE1 knockdown. Moreover, the IE1-binding fragment TKTL2-C1 acted as a competitive inhibitor that disrupted the IE1-TKTL2 interaction, decreased PPP flux, and reduced viral replication. Together, these findings demonstrate that WSSV IE1 directly activates host TKTL2 to rewire pentose phosphate metabolism, revealing a novel metabolic mechanism of viral pathogenesis and identifying the PPP as a potential target for antiviral intervention in aquaculture.

Advancing Plasmodium vivax malaria treatment in India: The vital role of glucose 6-phosphate dehydrogenase point-of-care tests

Advancing Obstetric Care: The Role of Targeted Next-Generation Sequencing in Pregnancies with Structurally Normal Fetuses.