Search Results (2,241)

In this study, we performed the first genome-wide identification and characterization of the cinnamoyl-CoA reductase (CCR) gene family in upland cotton (Gossypium hirsutum), focusing on its potential association with stem strength. We identified 76 GhCCR genes and classified them into four subfamilies. We then analyzed their evolutionary relationships, conserved domains, synteny, promoter cis-elements, and expression patterns. All GhCCR proteins possess the NADB_Rossmann superfamily domain, and family expansion appears to have been driven mainly by segmental and tandem duplications. A small number of GhCCR genes showed relatively high expression in leaf, pistil, and torus tissues, while genes such as GhCCR3/9/10 exhibited elevated transcript levels under abiotic stress conditions. RT-qPCR results indicated that three candidate GhCCR genes (GhCCR25, GhCCR52 and GhCCR64) were significantly more highly expressed in multiple tissues of the stiff-stem line JY-25 than in the soft-stem line JR-15. Together, these findings suggest that GhCCR genes may contribute to the regulation of growth, development, and stress adaptation in G. hirsutum. However, direct biochemical or genetic validation is required to confirm their functional roles in lignin biosynthesis and stem rigidity. Full article

Background/Objectives: Precision nutrition informed by genetic profiling has been proposed to improve public health outcomes; however, long-term, community-based evidence remains limited. This study evaluated the long-term health and economic impacts of the Sakado Folate Project. Methods: Since 2006, residents participating in the Sakado Folate Project received gene-guided nutritional counseling focused on folate intake and related lifestyle factors. Target genes included methylenetetrahydrofolate reductase (MTHFR), angiotensinogen (AGT), adrenoreceptor B3 (ADRB3), and uncoupling protein 1 (UCP1); Δ5-fatty acid desaturase (FADS1) was incorporated later. Biochemical markers, genetic polymorphisms, and health indicators were monitored longitudinally. Population-level health outcomes and per-capita medical expenditure data were compared with regional and national statistics. Results: In program participants (n = 888), folate status and biochemical indicators improved: 76.1% achieved the serum folate target (≥9.5 ng/mL) and 55.3% achieved the serum total homocysteine target (≤7 μmol/L). Healthier lifestyle behaviors were observed across 99,565 Sakado residents, with the city recording the highest proportion of individuals actively attempting lifestyle improvement (31%) of all districts in the region. Disease prevalence was lower in Sakado City than in Saitama Prefecture overall, at standardized prevalence ratios of 52% for stroke and 86% for cerebral infarction. Per-capita medical expenditure was also lower in Sakado City (¥337,800) than the national average (¥392,044) in 2021. Conclusions: Long-term implementation of a community-based, gene-guided nutritional intervention may improve population health outcomes and reduce healthcare expenditures. Integrating nutrigenomics into public health strategies alongside community education and food environment improvements may contribute to sustainable healthcare systems in aging societies. Full article

Heat stress (HS), increasingly intensified by climate change, severely restricts tomato growth and productivity. Although core heat shock factor-mediated transcriptional networks have been extensively characterized, how lipid metabolic reprogramming is transcriptionally coordinated during thermotolerance remains unclear. Using SlHDZ19 overexpression and mutant lines together with transcriptomic, biochemical, promoter-binding, and gene-silencing analyses, we show that the homeobox-leucine zipper transcription factor SlHDZ19 promotes tomato (Solanum lycopersicum) thermotolerance by activating a PLA2-dependent lipid-metabolic transcriptional program in leaves. SlHDZ19 overexpression generally improved heat-stress performance, while SlHDZ19 mutant lines exhibited heightened sensitivity, including more severe wilting, higher electrolyte leakage, and reduced proline accumulation and CAT activity under heat stress. Transcriptomic analysis revealed that SlHDZ19 is required for the full induction of canonical heat-responsive genes and that the linoleic acid metabolism pathway was repeatedly implicated in SlHDZ19-dependent transcriptional changes. SlHDZ19 binds to and activates the promoters of SlPLA_2α, which encodes a phospholipase A2 involved in releasing linoleic acid from membrane lipids, and three lipoxygenase genes (SlLox7, SlLox8, and SlLoxC), accompanied by elevated overall PLA2 and LOX activities in SlHDZ19-overexpressing plants. Moreover, genetic silencing of SlPLA_2α in both wild-type and SlHDZ19-overexpressing backgrounds supported its functional requirement downstream of SlHDZ19 in thermotolerance. Collectively, our findings support a thermotolerance module in which SlHDZ19 transcriptionally regulates PLA2- and LOX-associated steps of linoleic acid metabolism, potentially linking lipid-associated signaling and membrane remodeling with heat stress adaptation in tomato. Full article

Background: Treatment-resistant obsessive–compulsive disorder (OCD) is a heterogeneous and clinically challenging condition. Growing evidence suggests alterations in glutamatergic signaling within cortico–striatal–thalamo–cortical circuits, including those involving medium spiny neurons (MSNs), as well as genetic factors affecting synaptic organization, although the biological mechanisms underlying differential treatment response remain incompletely understood. Methods: This multicenter study presents a translational research framework aimed at investigating potential molecular and cellular correlates of treatment response in a cohort of patients with OCD, stratified according to their response to pharmacological treatments and transcranial magnetic stimulation (TMS). Peripheral blood mononuclear cells from clinically defined subgroups are reprogrammed into human induced pluripotent stem cells and differentiated into MSN-enriched neuronal cultures, enabling in vitro investigation of morphological, biochemical, and transcriptomic features associated with different clinical profiles. Optogenetic and pharmacological stimulation paradigms are applied to probe selected aspects of neuronal activation in vitro, providing a controlled and simplified experimental framework to explore cellular responses under different treatment conditions. By integrating clinical phenotyping with patient-derived cellular models, this study establishes a translational platform for hypothesis generation in the investigation of treatment response in OCD. Results and Conclusions: Preliminary clinical observations from an initial cohort undergoing neuromodulation are also reported to document feasibility and early clinical implementation of the study, providing an initial characterization of the cohort. Full article

Plants are constantly exposed to a wide range of abiotic stresses that have significant negative impacts on growth and yield. Plant acclimation to these stresses is governed by integrated classical phytohormone and plant peptide hormone signalling networks that control the ability of a plant to survive and adapt to extreme environments. Classical phytohormones, including abscisic acid, auxins, gibberellins, cytokinins, jasmonates, salicylic acid, brassinosteroids, and the recently recognised phytomelatonin, act in concert with peptide-based plant hormones, among which C-terminally encoded peptides (CEPs) play prominent roles in coordinating stress perception, signal transduction, and adaptive responses throughout the plant. These integrated networks control stomatal behaviour, photosynthesis, osmolyte and antioxidant levels, root architecture, and energy metabolism, thereby helping plants maintain homeostasis and optimise survival while sustaining minimal growth under unfavourable conditions. Under stressful conditions, these networks do not operate in isolation but form highly dynamic, context-dependent regulatory circuits in which each physiological process is simultaneously regulated by multiple hormones acting through convergent and overlapping signalling pathways. Phytomelatonin has emerged as a particularly important integrative node within these networks, functioning both as a potent direct antioxidant through sequential ROS-scavenging catabolite cascades and as a bidirectional regulator of classical phytohormone signalling under diverse abiotic stresses. New technologies in the fields of transcriptomics, proteomics, phosphoproteomics, metabolomics, and systems biology have provided new information on the dynamic relationships between classical phytohormones and plant peptide hormones, revealing candidate regulatory nodes and transcription factor networks that mediate stress adaptation at molecular, biochemical, and physiological levels. However, it is important to distinguish between correlative associations identified through omics profiling and causal regulatory relationships validated through rigorous genetic and biochemical experimentation, as most omics-derived candidates remain to be functionally established. Empirical studies demonstrate how these networks can be used to improve crops by increasing stress tolerance through modulating classical phytohormone and plant peptide hormone signalling, including through exogenous phytomelatonin application, CRISPR-mediated hormone pathway editing, and CEP pathway manipulation, to produce resilient cultivars without reducing yields. Although these advances represent significant progress, challenges remain, including the inherent complexity and redundancy of the networks, context-dependence and severity-dependence of hormonal responses, the persistence of a significant translational gap between laboratory findings and field application, and incomplete mechanistic understanding of peptide hormone roles under combined stress conditions. Addressing these challenges will require integrative multi-omics approaches, higher-order computational modelling, and rigorous field-based functional validation alongside emerging tools such as synthetic biology and precision breeding. Full article

Carotenoids are an important class of natural compounds, essential for human nutrition, acting in plants as pigments and apocarotenoid precursors. Tomato is a key model for carotenoid metabolism, as genetic variation strongly affects carotenoid composition during fruit ripening. To date, most of the enzymes involved in the carotenoid pathway were mainly characterized by linking gain- or loss-of-function phenotypes to their genetic basis (e.g., mutation in a single gene), with limited integration into pathway-wide analyses. Here we report an extensive biochemical and molecular characterization of a collection of tomato carotenoid mutants—apricot (at), yellow flesh (r), tangerine (t), Delta (Del) and Beta (B)—throughout three different stages of fruit ripening (mature green, breaker, red ripe). Using correlation-based integrative analyses, we integrated targeted isoprenoid metabolomics (carotenoids, chlorophylls, tocochromanols, quinones, abscisic acid) with gene expression profiling and correlation-based analyses. The pronounced, stage-dependent remodeling of the isoprenoid profiles exceeded the expected changes in substrates/products and was accompanied by significant transcriptional changes, largely independent of the position of the mutated step in the pathway. This integration highlighted metabolite/transcript regulatory links and the central role of lycopene cyclization in isoprenoid metabolism rewiring, thus improving our understanding of mechanisms controlling their accumulation during tomato fruit ripening. Full article

Obesity is a complex metabolic disorder resulting from interactions among genetic, environmental, and dietary factors. Traditional clinical markers may provide limited insight into the biochemical mechanisms that link nutrition and metabolic dysfunction; in this context, the epigenetic mechanisms through which nutrients modulate gene expression are central to understanding metabolic homeostasis. This review summarizes the published evidence on nutrient-driven epigenetic processes in obesity, focusing on DNA methyl donors, such as folate, vitamin B12, choline, betaine, serine, and methionine, and their effects on methylation and DNA methyltransferase activity. Metabolites such as acetyl-CoA, NAD⁺, and short-chain fatty acids (SCFAs) can also influence histone modifications, while diet-responsive microRNAs can regulate networks involved in adipogenesis, lipid metabolism, inflammation, and insulin signaling. Recent studies have identified epigenetic signatures associated with adiposity and metabolic traits, many of which are linked to the risk of cardiometabolic disease. This review is structured around the concept that nutrient-sensitive epigenetic mechanisms act as candidate biomarkers, linking dietary exposure to metabolic dysfunction. Recent evidence supports the idea that nutrient–epigenetic variation could complement traditional metabolic evaluations by offering mechanistic insight and translational direction. These findings suggest that nutrient-sensitive epigenetic mechanisms are biologically plausible candidate biomarker layers; however, their clinical implementation is currently limited by issues including tissue specificity, reproducibility, and the need for prospective validation. Full article

N⁶-methyladenosine (m⁶A) is an important epigenetic modification of eukaryotic RNA, playing a significant role in various biological processes. Metasequoia glyptostroboides (M. glyptostroboides) is an ancient tree species in China, with a long history and excellent genetic characteristics. In this study, we identified six MgYTH genes in the genome of M. glyptostroboides, elucidating their phylogenetic relationships, conserved domains, gene structures, conserved motifs, chromosome locations, and prediction of LLPS. The analysis of the cis-regulatory elements in the promoter region suggested that MgYTH genes are associated with drought and the ABA-responsive expression patterns signaling pathway, which was further supported by expression pattern analysis. In addition, to directly evaluate the m⁶A binding ability of MgYTH proteins, we selected MgYTH5 as the representative for homology modeling analysis and electrophoretic mobility shift assay (EMSA). The results demonstrated that MgYTH5 has the ability to bind m⁶A in vitro, thereby providing biochemical evidence that MgYTH5 can bind m⁶A-modified RNA in vitro mRNAs. The subcellular localization results showed that MgYTH5 is located in the cytoplasm. These findings provide new insights into the epigenetic regulation mechanisms in gymnosperms and provide a resource for future functional studies in this species. Full article

Background: An individual’s health status is determined by the interaction of genetic, environmental, social, and lifestyle variables. Nutrition plays a fundamental role in disease prevention, a notion widespread among the informed public, which is keen on participating in initiatives for personalized recommendations informed by advanced biological data. Objectives: To evaluate whether a personalized nutrition service can produce measurable changes in nutritional behavior and biological outcomes, we established the GENIE digital platform. This platform delivers personalized online food shopping and recipe recommendation informed by integrated data from (i) biochemical blood markers, (ii) nutrigenetic profiles, (iii) gut microbiota composition, and (iv) consumer preferences. Methods: We conducted a single-arm study in a Spanish cohort that used a specific online retailer for food shopping, totaling 1177 participants. Group 1 (n = 620) had recommendations based only on the biochemical blood test; Group 2 (n = 357) included the nutrigenetic test; and Group 3 had the gut microbiome test (first batch, n = 200; second batch, n = 97). After one month of informed, tailored dietary advice, a quantitative evaluation of the experience was conducted. Results: The GENIE platform led to strong engagement (mean session time 7.07 min; +154% e-commerce use), with 71% of participants following at least part of the recommendations. This was associated with an increase in microbiome diversity in about 70% of participants, after just one month of guided recommendations. Conclusions: The GENIE platform represents a pragmatic model for translating nutrigenetic and microbiome data into actionable dietary recommendations, bridging the gap between scientific evidence and consumer behavior. Full article

Soil acidity is a major constraint in many agricultural regions, where increased aluminum (Al³⁺) solubility at low pH severely affects plant health by inhibiting root elongation, disrupting nutrient uptake, and inducing oxidative stress. Recent studies have highlighted melatonin, a widely occurring indoleamine with strong antioxidant and stress-modulating properties, which alleviates Al-induced damage in crops. This review synthesizes current physiological, biochemical, and agronomic evidence demonstrating that exogenous melatonin enhances plant tolerance to aluminum toxicity. Across multiple model and crop species, melatonin application has been shown to improve root elongation by 20–45%, reduce lipid peroxidation by 30–60%, and enhance key antioxidant enzymes such as SOD, POD, and CAT by 25–70% under Al stress. Case studies in soybean, wheat, maize, and rice further indicate that melatonin protects root meristems from oxidative damage, stabilizes photosynthetic machinery, and improves nutrient acquisition. In acidic soils (pH 4.5), melatonin-treated soybean exhibited 28% greater biomass and 15–22% higher N and P uptake, while wheat plants demonstrated 10–18% higher grain filling under field-simulated Al stress. Emerging long-term studies show that melatonin also benefits soil health. Multi season experiments reveal that melatonin enhances root exudates that support beneficial rhizosphere microbes, increases soil enzymatic activities (urease, phosphatase) by 20–35%, and lowers exchangeable Al by 12–18%. These improvements contribute to cumulative yield gains of 10–18% over successive cropping cycles. Additionally, genetic approaches aimed at increasing endogenous melatonin levels in plants have demonstrated 12–30% yield improvement in acid soil conditions. This review highlights the need for multi-year, multi-location studies to further clarify how melatonin can support sustainable agricultural practices, enhance soil fertility, and mitigate aluminum toxicity in acid-affected regions. Full article

Background/Objectives: Familial hyperaldosteronism type IV (FH-IV) is an extremely rare, clinically heterogeneous condition representing the least characterized familial subtype of primary aldosteronism (PA) caused by germline gain-of-function CACNA1H mutations. Despite growing molecular insights, optimal diagnostic and therapeutic strategies remain poorly defined. This systematic review aims to synthesize available evidence regarding the clinical, biochemical, and genetic characteristics of FH-IV, and to evaluate the efficacy of current pharmacological and surgical treatments. Methods: A systematic review was conducted in accordance with PRISMA guidelines and preregistered in PROSPERO (CRD420261324945). A comprehensive search of MEDLINE, Embase, and Web of Science identified studies reporting genetically confirmed FH-IV patients. Data concerning clinical phenotypes, diagnostic evaluations, treatment outcomes, and genetic backgrounds were extracted and analyzed. Results: The primary cohort included 31 fully characterized symptomatic patients, alongside 8 mutation-positive relatives (4 asymptomatic carriers and 4 symptomatic individuals). The genetic landscape was remarkably heterogeneous, encompassing 17 distinct CACNA1H mutations. Clinically, diagnosis was frequently delayed, often complicated by atypical normokalaemic presentations and misleading adrenal imaging. Surgical treatment was generally ineffective, frequently resulting in persistent or recurrent hypertension and biochemical dysregulation. Pharmacologically, patients often required multiple antihypertensive drugs, most frequently a combination of mineralocorticoid receptor antagonists (MRAs) and calcium channel blockers (CCBs). Conclusions: FH-IV is best conceptualized as a systemic adrenal channelopathy. While standard screening parameters are usually elevated, atypical biochemical profiles and misleading structural imaging can complicate the diagnostic process. Optimal management relies on multigene Next-Generation Sequencing (NGS) panels for definitive diagnosis and cascade screening of relatives. Finally, while the combination of MRAs and CCBs is commonly used in PA, it represents a valuable therapy for FH-IV, with dual L-/T-type CCBs emerging as a potential disease-specific option. Full article

Background: Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive disorders caused by impaired adrenal steroidogenesis, most frequently due to pathogenic variants in the CYP21A2 gene leading to 21-hydroxylase deficiency (21-OHD). Epidemiology and management vary across the Mediterranean Basin as a result of genetic and healthcare differences. Objective: To provide an overview of the epidemiology, diagnostic approaches and treatment patterns of CAH in Mediterranean countries. Methods: A structured review of the literature was performed using PubMed, using combined disease-related, geographic and methodological terms. Eligible studies reporting on epidemiology, diagnosis, or management of CAH were included. Data on study design, population characteristics, incidence, diagnostics, genetics and treatment availability were extracted. Results: Data were collected from 23 Mediterranean and neighboring regions covering over 8.7 million screened newborns. In countries with established newborn screening (e.g., Spain, Italy, France, Greece), the incidence of classic CAH ranged from 1:10,000 to 1:25,000 live births. Higher rates were reported in parts of North Africa and the Eastern Mediterranean. Diagnostic set-up and access to biochemical and genetic confirmation varied widely. Hydrocortisone remains the primary therapy, while access to mineralocorticoids and modified-release glucocorticoids differed across settings. Conclusions: Overall, considerable heterogeneity in CAH epidemiology and care exists across the Mediterranean region. Genetic factors such as founder effects, consanguinity and healthcare organization contribute to these differences. Expanding newborn screening, improving diagnostics and availability to treatments are critical to reducing disparities in CAH care. Full article

Salinity stress is one of the major obstacles to glycophytic crop production worldwide, including rice. It alters cellular metabolism, causing significant crop destruction that results in substantial reductions in yield. The overexpression of C₄ enzymes, such as phosphoenolpyruvate carboxykinase (PEPCK), at high levels in C₃ transgenic plants through genetic engineering can decrease oxidative stress while increasing photosynthetic capabilities. In this research, we evaluate the efficiency of transgenic rice plants (Oryza sativa L. cv. IR64) overexpressing PEPCK genes in mitigating salinity stress and increasing photosynthetic efficiency. The T1 transgenics showed increased levels of several biochemical factors, including ascorbate peroxidase (APX), catalase (CAT), proline, glutathione reductase (GR), and guaiacol peroxidase (GPX) activities. This was accompanied by reduced levels of malondialdehyde (MDA), hydrogen peroxide (H₂O₂), and electrolytic leakage, suggesting an effective antioxidant defense mechanism against the oxidative damage driven by salt stress. Photosynthetic parameters—such as chlorophyll content, net photosynthetic rate, intercellular CO₂ content, and stomatal conductance—were elevated in transgenic plants compared to control plants. The transgenics also exhibited superior agronomic characteristics. Our findings provide conclusive evidence of the PEPCK gene’s potential role in regulating salt stress response and tolerance in rice plants. Full article

Escherichia coli, a facultative anaerobic Gram-negative member of the Enterobacteriaceae, is an increasingly important opportunistic pathogen driven in part by rising resistance to clinically important antibiotics. Regulation of multidrug efflux systems by two-component signal transduction pathways, particularly the BaeSR system, plays a central role in this process. However, the functional residues governing signal transduction through the sensor kinase BaeS remain incompletely defined. In this study, we integrated domain prediction, homology-guided site-directed mutagenesis, in vitro protein purification, autophosphorylation assays, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR)-based transcriptional analysis of selected BaeSR-regulated genes to delineate key residues required for BaeS function. Sequence analysis identified His250 as a candidate autophosphorylation site and Asn364 as a conserved residue within the catalytic domain. Biochemical characterization of purified wild-type BaeS and an H250A mutant demonstrated that His250 is indispensable for autophosphorylation. Consistently, RT-qPCR analysis showed that BaeS activation markedly induced the transcription of BaeSR-regulated efflux-associated genes, whereas genetic deletion of baeS or selective disruption of kinase activity by the N364A mutation abolished this response. Together, these findings establish His250 as a key residue for BaeS autophosphorylation and identify Asn364 as essential for inducible BaeSR signaling and activation of resistance-associated target genes, thereby establishing an experimental framework for elucidating BaeSR-mediated efflux regulation and informing future studies of resistance regulatory networks and potential intervention strategies centered on key signaling nodes. Full article

Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism caused by ATP7B mutations, characterized by hepatic copper accumulation and multisystem involvement. Several rare inherited and acquired conditions can closely mimic WD, posing diagnostic challenges and the risk of inappropriate therapy. By examining neuroimaging patterns and distinguishing between diagnostic criteria, this narrative review provides a comprehensive synthesis of WD-mimicking disorders, emphasizing their molecular mechanisms, clinical phenotypes, and biochemical features. WD-mimicking disorders encompass ATP7A-related neurodegenerations (Menkes disease, occipital horn syndrome, X-linked distal hereditary motor neuropathy), MEDNIK syndrome, Huppke–Brendel syndrome, aceruloplasminemia, congenital disorders of glycosylation, primary familial intrahepatic cholestasis type 3, and acquired copper deficiency syndromes. Mechanisms include systemic copper deficiency, impaired intracellular trafficking, defective ceruloplasmin biosynthesis, secondary hepatic copper accumulation, and abnormal glycosylation. Clinical features range from neurodevelopmental delay, movement disorders, and hepatic dysfunction to dermatologic, hematologic, and connective-tissue abnormalities. Biochemical profiles may overlap with WD, particularly low serum ceruloplasmin and total copper, altered urinary copper excretion, and elevated hepatic copper in some disorders. Neuroimaging and genetic testing provide critical discriminative value. Management is largely supportive, with disease-specific therapies available in selected conditions, such as subcutaneous copper in Menkes disease or monosaccharide supplementation in certain congenital disorders of glycosylation subtypes. Accurate differentiation between WD and WD-mimicking disorders requires careful integration of clinical, biochemical, imaging, and molecular data. Recognition of distinctive features and understanding underlying pathophysiology are essential to avoid misdiagnosis and inappropriate anti-copper therapy, optimize management, and improve patient outcomes. Full article