Search Results (378)

Newborn screening (NBS) is a critical component of the three-tiered prevention strategy for birth defects, reducing congenital disorder burden and improving long-term child health outcomes. Over the past 45 years, NBS in China has evolved into a nationwide quality-controlled network driven by policy support and technological advances. Currently, phenylketonuria and congenital hypothyroidism are included in universal NBS across the country, and several provinces have expanded to encompass congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase deficiency, and additional inherited metabolic disorders identified through tandem mass spectrometry. The application of next-generation sequencing and other technologies has further enhanced detection capacity and expanded detectable disease spectra. Meanwhile, the National Quality Management System for NBS (QMS-NBS) has realized the visualization and standardization of screening quality and performance. Despite these advances, challenges remain, including regional disparities, inadequate follow-up, and long-term management. This review summarizes the historical evolution and policy framework of NBS in China, outlines the development of screening institutions, the spectrum and incidence of screened disorders, advances in detection technologies, and the establishment of QMS-NBS. It also highlights future priorities: expanding screened conditions, strengthening follow-up and long-term care, promoting regional equity, and advancing novel technologies to improve child health and foster precision public health. Full article

Streptococcus cristatus (S. cristatus) belongs to the viridans group of streptococci and is a commensal of the human upper respiratory tract. With the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase, GapN, and the oxidative part of the pentose phosphate pathway (oxPPP), S. cristatus can use two different metabolic pathways to provide reduced nicotinamide adenine dinucleotide phosphate (NADPH), an essential cofactor of anabolic reactions such as fatty acid and amino acid biosynthesis. Regarding their NADP-reducing capacity, streptococci can be categorized into three groups: those that have only GapN, those that use only the oxPPP, and those that use both pathways. Here, we report on the experimental and computational characterization of the catalytic properties of the three NADP-reducing enzymes: GapN, glucose-6-phosphate dehydrogenase (G6PDH), and 6-phosphogluconate dehydrogenase (6PGDH) of S. cristatus. Kinetic analyses showed moderate substrate and cofactor affinities, with GapN displaying the tightest substrate binding, followed by 6PGDH and G6PDH, in agreement with structural and computational predictions. All three enzymes preferentially utilized NADP⁺, with only G6PDH exhibiting limited NAD⁺ promiscuity. Growth-phase-dependent activity patterns suggest dynamic adjustment of NADPH-generating pathways, with reduced GapN contribution and sustained oxPPP activity in the stationary phase. Regulatory screening indicated limited allosteric control, though feedback inhibition by NADPH and the ATP sensitivity of G6PDH point to conserved redox regulatory mechanisms. Comparative analysis across streptococci supports the concept that the coexistence of GapN and the oxidative pentose phosphate pathway in S. cristatus may provide metabolic flexibility by offering alternative routes for NADPH generation. Full article

Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article

Low-frequency alternating magnetic field (LF-AMF) was applied to liquid fermentation of Pleurotus citrinopileatus for the production of extracellular polysaccharides (EPS). Two types of EPS (POL1 and POL2) were secreted by P. citrinopileatus under normal fermentation conditions, while only one type of EPS (POL3) was produced under LF-AMF-assisted fermentation. The study demonstrated that LF-AMF-assisted fermentation altered the monosaccharide composition, molar ratios of component monosaccharides, and molecular weight distribution of EPS. LF-AMF enhanced the flocculation activity of EPS in a concentration-dependent and dosage-specific manner. Transcriptomic analysis revealed a total of 32,413 differentially expressed genes (DEGs) (|log2(fold-change)| ≥ 1, p < 0.05) between P. citrinopileatus under LF-AMF-assisted fermentation and normal fermentation. Of those, 5818 genes were up-regulated and 26,595 genes were down-regulated. The DEGs were enriched in metabolic pathways and biosynthesis of secondary metabolite. Genes involved in glycolysis and gluconeogenesis, such as hexokinase, 6-phosphofructokinase, fructose-1,6-phosphate aldolase, glyceraldehyde 3-phosphate dehydrogenase and glucose-1,6-diphosphatase were up-regulated. Additionally, genes in the tricarboxylic acid (TCA) cycle, including citrate synthase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase were also up-regulated. These findings suggest that LF-AMF-induced transcriptional alterations in glycolysis may modulate the metabolic supply of precursors for EPS biosynthesis, thereby affecting the biosynthetic process and altering the compositional characteristics of EPS. Full article

Antisense oligonucleotides (ASOs) are short, synthetic DNA fragments able to modulate gene expression. In this work, the cytosolic isoform of glucose-6-phosphate dehydrogenase (Cyt-G6PDH) was selected as a target for ASOs to induce transient gene silencing in barley (Hordeum vulgare). G6PDH is the most important enzyme of the oxidative pentose phosphate pathway (OPPP), supplying NADPH and regulating the entire cycle. Different ASOs were tested at different concentrations on the leaf surface. Their effects were evaluated by measuring enzymatic activity, gene expression, and protein abundance. Treatment with 30 µM ASOs for 6 h represented the optimal condition, inducing a 40–60% reduction in G6PDH total activity in barley leaves, with a specific decrease in the cytosolic isoform, as determined by DTT-sensitive enzymatic assays. ASOs designed on the main regulator of cyt-G6PDH, the shaggy-like kinase (SK11), led to an analogous effect in terms of G6PDH activity, confirming the involvement of HvSK11 in the regulation of cyt-G6PDH in barley. Consistently, qRT-PCR analyses showed that ASO treatment simulates an abiotic stress condition obtained by the down-regulation of Cyt-G6PDH. These results support the use of ASOs as a rapid and efficient method for the functional analysis of key metabolic regulators in plants to overcome complications in recalcitrant organisms or lethal genes. Full article

Sweet and sour flavors are the most important indicators of loquat fruit quality; they are determined not only by variety but also by the flesh type and the concentration and change patterns of sugars, organic acids, related enzyme activities, and endogenous phytohormones. This study aimed to comprehensively evaluate the physiological and biochemical characteristics associated with loquat fruit flavor formation by analyzing the changes and correlation in sugars, organic acids, enzyme activities, and endogenous hormones during fruit development in the white-fleshed, high-sugar cultivar ‘Qixing’ and the red-fleshed, sour–sweet cultivar ‘Huoju’. The results indicated a significant increase in total soluble sugars and individual sugars (mainly fructose, glucose, and sucrose), and a sharp decrease in organic acids (mainly malic acid). Correlation analysis revealed that the activities of sucrose synthase (SS), sucrose phosphate synthase (SPS), and phosphofructokinase (PFK) were positively associated with sugar accumulation. In contrast, phosphoenolpyruvate carboxylase (PEPC), NADP-malic enzyme (NADP-ME), and NAD-malate dehydrogenase (NAD-MDH) were crucial for organic acid metabolism. Phytohormone analysis indicated that indole-3-acetic acid (IAA) and gibberellic acid (GA₃) play vital roles in fruit enlargement, while abscisic acid (ABA) is important for fruit ripening in loquats. These findings provide insights into the physiological mechanisms underlying loquat fruit quality formation, reveal the enzymatic or hormonal regulatory effects on sugar accumulation and acid degradation, and provide a theoretical basis for improving the fruit flavor quality. Full article

The Warburg effect is better understood as regulated metabolic plasticity rather than mitochondrial failure. Many malignant cells retain functional mitochondria while increasing aerobic glycolysis, lactate production, and redox remodeling to support growth, immune escape, and adaptation to microenvironmental stress. Within the context of the cancer microenvironment, this review examines xylitol as a hypothetical metabolic modifier within a broader host-microbe-mitochondria framework. Xylitol, a five-carbon sugar alcohol, is derived endogenously through the pentose phosphate pathway (PPP) and the glucuronate–xylulose pathway, and is metabolized efficiently in humans, rats, and pigs through xylitol dehydrogenase (XDH) in hepatic mitochondria and the cytosol; whereas, it is less tolerated by obligate carnivores who lack this enzyme. Preclinical studies show that partial substitution of glucose with xylitol can reduce proliferation and glycolytic markers in oral squamous carcinoma models, and preliminary studies link xylitol to glutathione depletion, endoplasmic reticulum (ER) stress, autophagy-associated death, and altered tumor metabolomics. On the other hand, oral pathogens such as Fusobacterium nucleatum and Porphyromonas gingivalis promote tumor stemness, extracellular vesicle signaling, metastasis, and immune evasion. In addition, Streptococcus mutans, the primary cariogenic pathogen, contributes to systemic bacteremia and epithelial–mesenchymal transition. Oral and gut microbiomes modulate macrophage polarization, T cell activity, and the senescence-associated secretory phenotype (SASP), possibly promoting cancer immune evasion. The anti-adhesive properties of xylitol may limit pathogen attachment to immune cell receptors, reducing the generation of pro-tumorigenic senescent immune cells. Xylitol also offers metabolic benefits, a low glycemic index, partial insulin-independent metabolism, and potential diabetes-prevention activity that are relevant, considering the established link between metabolic disease and cancer risk. A recent study reported that higher levels of endogenous xylitol were associated with adverse cardiovascular events, but confirmation of this requires large scale prospective studies. The evolutionary dietary context of MIS 6, during which hominin populations in sub-Saharan Africa depended on polyol-rich underground storage organs, provides a biological basis for human tolerance of xylitol. As a result, we hypothesize that xylitol may be a context-dependent metabolic modifier within an integrated host–microbe–mitochondria–cancer stem cell network. Full article

Age-related hyperphosphatemia is increasingly recognized as a contributing factor in sarcopenia. This work studies the metabolic effects of elevated phosphate on muscle. C2C12 cells were differentiated in the absence or presence of 10 mM β-glycerophosphate (BGP), an exogenous phosphate donor. In addition, quadriceps muscles from four experimental groups of male C57BL/6J mice were analyzed: young (5 months) and old (24 months) fed with standard diet; old mice fed with hypophosphatemic diet or supplemented with the phosphate binder Velphoro^®, for the last three months of life. Mice were stratified according to sarcopenia degree based on muscle mass, strength and physical performance. Protein levels were determined by immunoblotting and mRNA expression by RT-qPCR. ATP levels were measured by luminescence and L-lactate production, citrate synthase and cytochrome c oxidase activities by colorimetric assays. Mitochondrial content, membrane potential and reactive oxygen species (ROS) were determined by fluorescence assay. BGP-treated cells showed increased glucose transporter 1 (GLUT1) and decreased NADH Dehydrogenase (CI-NDUFB8) protein expression, elevated hexokinase II (HK2), phosphoglycerate kinase 1 (PGK1) and lactate dehydrogenase A (LDHA) mRNA levels, reduced ATP levels, increased lactate production, and decreased mitochondrial enzyme activities. Moreover, BGP increased ROS, diminished mitochondrial membrane potential, and altered fusion–fission dynamics and mitophagy. In aged quadriceps, oxidative phosphorylation (OXPHOS) subunits and superoxide dismutase 2 (SOD2) expression were reduced. The hypophosphatemic diet improved all parameters, whereas Velphoro^® selectively increased Mitochondrial cytochrome C oxidase subunit 1 (CIV-MTCO1) expression. Several altered mitochondrial markers are associated with sarcopenia degree. Altogether, hyperphosphatemia induces metabolic changes that scale with the sarcopenic degree. Our findings show a relevant association between hyperphosphatemia and mitochondrial dysfunction, and they support the potential benefit of phosphate reduction as a strategy to prevent or mitigate sarcopenia. Full article

Background/Objectives: Betanin (Bet), a natural compound, exhibits potent antioxidant and metabolic regulatory properties, yet its effect on cellular glucose utilization remains unclear. This study investigated, for the first time, the impact of Bet on glucose consumption and the activation of key carbohydrate–catabolic pathways in human erythrocytes. Methods: In vitro assays were performed to evaluate enzyme inhibition and activation. Human erythrocytes were incubated with Bet to assess glucose consumption. Enzyme activities were measured spectrophotometrically, and molecular docking was used to analyze binding interactions. Results: Our results demonstrate that Bet inhibits digestive enzymes in a dose-dependent manner, with maximal inhibition at 90 µg/mL for pancreatic lipase and 70 µg/mL for α-amylase, showing IC₅₀ values of 48.8 and 31.9 µg/mL, respectively, supported by strong binding affinities of −9.3 and −8.9 Kcal/mol. These interactions are stronger than those of orlistat (−6.9 Kcal/mol) and acarbose (−7.7 Kcal/mol). Bet also induced the activity of AMPK with an IC₅₀ of 1.83 µg/mL and a BE of −7.90 Kcal/mol, compared to the specific AMPK activator A-769662, which had an IC₅₀ of 1.29 µg/mL and a binding energy of −10.0 Kcal/mol. Consequently, Bet stimulated key glycolytic enzymes, reaching maximal activation (~62%) at 1.4 µg/mL for hexokinase (HK) and glucose-6-phosphate dehydrogenase (G6PD), and at 1.6 µg/mL for pyruvate kinase (PK), supported by binding energies of −7.2, −7.5, and −9.0 Kcal/mol and AC₅₀ values of 0.87, 0.98, and 0.91 µg/mL, respectively. Moreover, Bet enhanced key Krebs cycle enzymes (IDH, SDH, MDH, LDH) in a dose-dependent manner, with AC₅₀ values of 0.76, 0.80, 0.72, and 0.52 µg/mL and strong binding energies (−7.8, −7.8, and −8.4 Kcal/mol), reaching maximal activation near 1.4 µg/mL. Bet also increased glucose consumption by human erythrocytes. Conclusions: Bet enhances glucose utilization by inhibiting digestive enzymes and activating intracellular metabolic pathways, suggest potential metabolic regulatory effects. Full article

Agaricus bisporus (A. bisporus) is susceptible to rapid postharvest deterioration. Although elevated CO₂ (6%) delays senescence, the metabolic mechanisms remain unclear. In this study, untargeted and targeted metabolomic analyses were employed to explore these pathways in A. bisporus. The results revealed that elevated CO₂ treatment promoted glycolysis by upregulating Hexokinase (HK), Phosphofructokinase (PFK), and Pyruvate Kinase (PK), accumulating Glucose-6-phosphate (G-6-P) and Fructose-6-phosphate (F-6-P). Concurrently, elevated CO₂ treatment upregulated the expression of genes associated with the tricarboxylic acid (TCA) cycle and increased the enzymatic activities of Malate Dehydrogenase (MDH) and Fumarate hydratase (FUM). These changes led to the rapid consumption of key intermediate metabolites (Fumarate (Fum), Malate (Mal), and α-Ketoglutarate (α-KG)), collectively enhancing the efficiency of the TCA cycle. Furthermore, elevated CO₂ treatment significantly suppressed the activities of Glutamine Synthetase (GS) and Xanthine Oxidase (XOD), inhibiting the synthesis of Glutamine (Gln) and Pyroglutamate (pGlu) while promoting the accumulation of Hypoxanthine (Hx). This coordinated reprogramming of amino acid metabolism and purine metabolism contributed to improved energy efficiency and enhanced cellular integrity in postharvest A. bisporus. This study elucidates the specific mechanism by which elevated CO₂ levels regulate the postharvest energy metabolism of A. bisporus from a metabolomics perspective, providing a theoretical basis for developing strategies to control its postharvest quality. Full article

Venous thromboembolism (VTE) is a major cause of morbidity and mortality, underscoring the need for new molecular markers to enable early detection and clarify underlying mechanisms. Iron metabolism is linked to oxidative stress, endothelial injury, and inflammation, all central to thrombosis, yet its transcriptomic contribution to VTE remains unclear. We analyzed gene expression profiles from GSE19151 and GSE48000 using differential expression and weighted gene co-expression network analysis (WGCNA), integrating results with an iron metabolism gene set. Three hub genes were identified, arachidonate 5-lipoxygenase (ALOX5), Rho GTPase activating protein 1 (ARHGAP1), and glucose-6-phosphate dehydrogenase (G6PD), all downregulated in VTE. Gene set enrichment indicated that ALOX5 is involved in endothelial regulation, lipid metabolism, and immune pathways. A three-gene signature showed high diagnostic accuracy (AUC = 0.924 in the discovery cohort; 0.705 in validation). Immune deconvolution revealed broad immune remodeling and associated ALOX5 with multiple immune cell subsets, especially M0 macrophages, and with regulators such as TGFB1 and IL6R. Western blot analysis further showed that ALOX5 protein expression was significantly increased in LPS-activated HUVECs, supporting its involvement in inflammatory endothelial injury. DrugBank screening identified 19 approved drugs targeting ALOX5, supporting its potential for mechanistic and clinical investigation. Full article

Bacterial peritonitis (BP) remains a significant clinical challenge due to its high risk of multiple organ failure and associated mortality. Neutrophils are central effectors of innate immunity, and their functional activity and metabolism may influence the progression and outcomes of immunoinflammatory diseases. To investigate the phagocytic activity and intracellular metabolic profiles of neutrophils in patients with BP and to evaluate their relationship with postoperative clinical outcomes, 51 patients with BP (23 men, 28 women; mean age 49.6 ± 9.4 years) were examined. Blood samples were collected preoperatively and on postoperative day 7. Phagocytic activity of total, actively, and weakly phagocytic neutrophils was assessed using flow cytometry. Intracellular activity of NAD(P)- and NAD(P)H-dependent oxidoreductases and dehydrogenases was measured by bioluminescence. Patients were stratified according to postoperative outcome: favorable (n = 32) or unfavorable (n = 19). Seventy healthy individuals served as controls. Preoperatively, the proportion and phagocytic activity of neutrophils were markedly elevated in all patients. Postoperatively, the proportion of phagocytosing neutrophils remained high; however, phagocytic activity increased in patients with favorable outcomes but decreased to control levels in those with unfavorable outcomes. Neutrophil metabolism before surgery exhibited activation of both anaerobic and aerobic pathways, accompanied by reduced glucose-6-phosphate dehydrogenase activity. Postoperative metabolic adaptations differed according to outcome: patients with favorable outcomes demonstrated normalization of energy metabolism, whereas patients with unfavorable outcomes exhibited enhanced anaerobic metabolism, persistent aerobic activity, increased substrate flux towards glutamate/glutamine synthesis, and intensified lipid peroxidation. Phagocytic activity and metabolic profiles of neutrophils in BP are outcome-dependent. Effective postoperative anti-inflammatory responses, including reverse migration of activated neutrophils, are associated with favorable outcomes, whereas persistent metabolic activation and oxidative stress correlate with unfavorable prognosis. Neutrophil functional and metabolic parameters may serve as prognostic biomarkers and potential targets for therapeutic modulation in BP. Full article

Niacin contents vary significantly among fresh-cut potato cultivars with different browning sensitivities, whereas its role as a browning inhibitor for fresh-cut produce has not been previously reported. In this study, potato slices were soaked in distilled water (control) or 1% food-grade niacin solution for 5 min, then stored at 4 ± 1 °C for 8 days with sampling every 2 days for physiological and molecular analyses. In particular, the optimal niacin (1%) treatment showed higher brightness and lower color change than the control. The activities of polyphenol oxidase (PPO), peroxidase (POD), and phenylalanine ammonia lyase (PAL), and phenol content were reduced. Higher activities of superoxide dismutase (SOD) and catalase (CAT), and greater glutathione accumulation, were observed following niacin treatment. Meanwhile, lower levels of malondialdehyde and reactive oxygen species (ROS), and lower nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity, indicated lower oxidant damage. The contents of NADP and NAD, and activities of nicotinamide adenine dinucleotide kinase (NADK) and glucose-6-phosphate dehydrogenase (G6PDH) were improved. Furthermore, the gene expression patterns of StRBOH, StPPO, and StG6PDH also supported the hypothesis that niacin regulates pyridine nucleotide and ROS homeostasis. Full article

Mucic acid (MA) is used as a chelating agent or as a building block for bio-based polymers. MA can be produced by regioselective oxidation of D-galacturonic acid (GA). Gluconobacter oxydans is known for the partial oxidation of various substrates via membrane-bound dehydrogenases. As the wild-type strain shows only low oxidation activity towards GA, the engineered multideletion strain G. oxydans BP9.1 pta-mGDH, overexpressing a membrane-bound glucose dehydrogenase from Pseudomonas taetrolens, was used in buffered whole-cell batch biotransformations with GA as the sole substrate. Initial cell-specific MA formation rates elevated with rising educt concentrations up to 63 g L⁻¹. At pH 4, full GA conversion was only achieved with an initial GA concentration of 10 g L⁻¹. Complete conversion of 94 g L⁻¹ of GA was achieved at pH 5 with 3.4 g L⁻¹ of G. oxydans BP9.1 pta-mGDH within 48 h, resulting in >100 g L⁻¹ of MA, corresponding to a yield of >99% (mol/mol). Isolation of MA (purity > 90%) was achieved after cell separation, followed by cooling crystallization and drying, with a yield of 94%. Complete, full-yield GA conversion using non-growing cells of engineered G. oxydans in simple phosphate buffer yielded high product concentrations and enabled simple, high-yield product isolation, thus resulting in cost-effective and sustainable bioproduction of MA. Full article

Adverse drug reactions (ADRs) remain a major public health issue, and genetic factors contribute importantly to interindividual variability in drug response. Pharmacogenetic testing helps reduce ADR risk by optimizing drug selection and dosage, particularly in monogenic disorders. Whole-exome sequencing of 6739 samples from the Russian population was performed on the DNBSEQ-G400 platform (MGI). Variants in 48 genes were examined, focusing on inherited arrhythmias, enzyme deficiencies (Glucose-6-Phosphate Dehydrogenase Deficiency [G6PDD], Porphyrias), Dravet Syndrome (DS) and Malignant Hyperthermia (MH). Variants reported as pathogenic (P), likely pathogenic (LP), or variants of uncertain significance (VUS) in ClinVar were manually re-evaluated using ACMG criteria. A total of 75 unique variants in 18 genes were observed in 119 individuals (1.77%), including 21 carriers and 13 women with a G6PD mutation. Of these, 44 variants were classified as P, 24 as LP, and 7 as VUS. Missense variants accounted for the largest proportion (73.33%). The most affected genes were KCNQ1 (24/119), which exhibited the highest number of unique variants (18), G6PD (20/119), SCN1A (15/119), and RYR1 (14/119). Regarding associated conditions, mutations linked to arrhythmias were found in 51 individuals, MH in 27, G6PDD in 20, DS in 15, and Porphyrias in 6. Integrating common and rare clinically actionable genetic variants with attention to penetrance and clinical validity may improve medication safety, reduce preventable ADRs, and enhance personalized pharmacotherapy. Full article