Treatment Response With Potassium-competitive Acid Blockers Based on Clinical Phenotypes of Gastroesophageal Reflux Disease: A Systematic Literature Review and Meta-analysis.

Background/Aims: Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Methods: Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. Results: In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Conclusions: Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

Glutathione Dynamics in the Tumor Microenvironment: A Potential Target of Cancer Stem Cells and T Cells.

Glutathione (GSH), the main cellular antioxidant, dynamically influences tumor growth, metastasis, and resistance to therapy in the tumor microenvironment (TME), which comprises cancer cells, immune cells, stromal cells, and non-cellular components, including the extracellular matrix, metabolites, hypoxia, and acidity. Cancer stem cells (CSCs) and T cells are minor but significant cell subsets of the TME. GSH dynamics influences the fate of CSCs and T cells. Here, we explored GSH dynamics in CSCs and T cells within the TME, as well as therapeutic approaches that could target these dynamics.

Social intelligence and pathological gaming: a longitudinal study of the associations among negative emotions, social intelligence, aggression, and pathological gaming in adolescents.

Introduction: Pathological gaming continues to be highlighted as one of the most critical issues concerning adolescents. Numerous studies have aimed to elucidate the relationships between adolescents' negative emotions (e.g., peer stress, anxiety, loneliness) and social factors (e.g., social skills and relationships) with pathological gaming. Despite the recognition of social intelligence as a crucial factor related to social factors in adolescents, there is a paucity of research examining pathological gaming and social intelligence through longitudinal analyses. Method: This study focuses on exploring the factors that induce or inhibit pathological gaming among adolescents by analysing three-year longitudinal data from Korean adolescent gamers (N=968). Using a structural equation model, the study examines the relationships between adolescents' negative emotions (e.g., peer stress, anxiety, loneliness), social intelligence, and pathological gaming to elucidate their associations. Results: The results indicate that negative emotions can potentially reduce levels of social intelligence and increase aggression. Increased aggression, in turn, appears to be associated with higher levels of pathological gaming. Social intelligence was found to impact pathological gaming potentially negatively and may exert a significantly stronger influence on aggression compared to negative emotions. Discussion: The study's findings suggest that bolstering adolescents' social aptitude and addressing mental health concerns could serve as beneficial interventions in tackling issues associated with excessive media engagement among youth. These findings suggest that, within the context of adolescent pathological gaming, social intelligence could significantly affect aggression and emerge as a key variable that may lead to pathological gaming.

Effects of ultraviolet rays and particulate matter on hair porosity in damaged hair.

BACKGROUND: With growing interest in hair health, researchers are exploring aspects beyond the surface qualities of hair, such as its porous inner structure. While previous studies have focused on the effects of treatments such as perming and hair dying on hair porosity, less emphasis has been paid to the effects of harmful environmental factors such as ultraviolet (UV) rays and particulate matter on the porous nature of hair. AIMS: The aim of this study was to bridge this gap by investigating how UV rays and particulate matter affect hair porosity in different ways. Our study could help elucidate how these external factors influence hair health and shed light on previously unknown aspects of hair porosity. METHODS: Hair tresses were bleached, cut into 1 cm-long sections, and stained with methylene blue. The sections were then irradiated with UV light or exposed to particulate matter. RESULTS: Bleached hair absorbed more methylene blue than normal hair. UV radiation-induced hair porosity occurred at 3 h after irradiation and increased with time. Particulate matter alone did not affect the porosity of the damaged hair; however, in combination with UV irradiation, it substantially increased hair porosity. CONCLUSION: Environmental challenges such as a depleted ozone layer and increasing pollution may increase hair porosity, which can be prevented by maintaining healthy hair.

Study of the soothing effects of troxerutin in alleviating skin sensitivity.

BACKGROUND: Transient receptor potential vanilloid 1 (TRPV1) is associated with skin sensitivity and mainly activated by capsaicin and heat. Interestingly, troxerutin can inhibit TRPV1 activation. However, its efficacy in reducing skin sensitivity remains undetermined. AIMS: We evaluated the efficacy of troxerutin in alleviating skin sensitivity using clinical tests and in vitro experiments. METHODS: For the in vitro experiment, HaCaT keratinocytes were pretreated with different concentrations of troxerutin, followed by incubation with 50 µM capsaicin for 1, 24, or 48 h. The gene and protein expressions of four inflammatory cytokines involved in skin irritation were determined. Among 35 Korean women with sensitive skin recruited for the clinical trial, 13 were involved in assessing the immediate soothing effects of 0.1% and 0.0095% troxerutin following capsaicin irritation, whereas 22 participated in evaluating the preventive soothing effect of 10% and 1% troxerutin over 4 weeks against capsaicin- and heat-induced irritation. We evaluated the soothing rate using skin redness, visual analog scale, and high temperature sensitive index as evaluation indices. RESULTS: Troxerutin inhibited the mRNA and protein expressions of cytokines in capsaicin-treated keratinocytes. In the clinical study, 0.1% and 0.0095% troxerutin promptly alleviated capsaicin-induced skin redness, whereas 10% troxerutin notably decreased both the visual analog scale and high temperature sensitive index for capsaicin- and heat-related irritation. However, 1% troxerutin was only effective in reducing the visual analog scale in response to capsaicin irritation. CONCLUSIONS: Troxerutin can inhibit TRPV1 activation in clinical and in vitro tests.

Phosphorylation of DNA-binding domains of CLOCK-BMAL1 complex for PER-dependent inhibition in circadian clock of mammalian cells.

In mammals, CLOCK and BMAL1 proteins form a heterodimer that binds to E-box sequences and activates transcription of target genes, including Period (Per). Translated PER proteins then bind to the CLOCK-BMAL1 complex to inhibit its transcriptional activity. However, the molecular mechanism and the impact of this PER-dependent inhibition on the circadian clock oscillation remain elusive. We previously identified Ser38 and Ser42 in a DNA-binding domain of CLOCK as phosphorylation sites at the PER-dependent inhibition phase. In this study, knockout rescue experiments showed that nonphosphorylatable (Ala) mutations at these sites shortened circadian period, whereas their constitutive-phospho-mimetic (Asp) mutations completely abolished the circadian rhythms. Similarly, we found that nonphosphorylatable (Ala) and constitutive-phospho-mimetic (Glu) mutations at Ser78 in a DNA-binding domain of BMAL1 also shortened the circadian period and abolished the rhythms, respectively. The mathematical modeling predicted that these constitutive-phospho-mimetic mutations weaken the DNA binding of the CLOCK-BMAL1 complex and that the nonphosphorylatable mutations inhibit the PER-dependent displacement (reduction of DNA-binding ability) of the CLOCK-BMAL1 complex from DNA. Biochemical experiments supported the importance of these phosphorylation sites for displacement of the complex in the PER2-dependent inhibition. Our results provide direct evidence that phosphorylation of CLOCK-Ser38/Ser42 and BMAL1-Ser78 plays a crucial role in the PER-dependent inhibition and the determination of the circadian period.

Discordance Rate and Risk Factor of Other Diagnostic Modalities for Small Bowel Tumors Detected by Device-Assisted Enteroscopy: A Korean Association for the Study of Intestinal Disease (KASID) Multicenter Study.

Background/Aims: Despite advances in imaging and endoscopic technology, diagnostic modalities for small bowel tumors are simultaneously performed. We investigated the discrepancy rate between each modality and predictive factors of discrepancy in patients with definite small bowel tumors. Methods: Data of patients with definite small bowel tumors who underwent both device-assisted enteroscopy (DAE) and computed tomography (CT) were retrieved from web-based enteroscopy registry database in Korea. Predictive risk factors associated with discrepancy were analyzed using logistic regression analysis. Results: Among 998 patients, 210 (21.0%) were diagnosed with small bowel tumor using DAE, in 193 patients with definite small bowel tumor, DAE and CT were performed. Of these patients, 12 (6.2%) showed discrepancy between examinations. Among 49 patients who underwent DAE and video capsule endoscopy (VCE) examination, 13 (26.5%) showed discrepancy between examinations. No significant independent risk factors were associated with concordance between DAE and CT in multivariate logistic regression analysis among the patients. In a multivariate logistic regression analysis, red blood cell transfusion was negatively associated with concordance between DAE and VCE in patients with small bowel tumor (odds ratio, 0.163; 95% confidence interval, 0.026 to 1.004; p=0.050). Conclusions: For small bowel tumors, the discrepancy rate between DAE and CT was 6.2%, and 26.5% between DAE and VCE. Despite developments in cross-sectional imaging (VCE and DAE modalities), discrepancies still exist. For small bowel bleeding that require significant transfusion while showing insignificant VCE findings, DAE should be considered as the next diagnostic approach, considering the possibility of missed small bowel tumor.

Penetration rates into the stratum corneum layer: A novel quantitative indicator for assessing skin barrier function.

BACKGROUND: The stratum corneum (SC), the outermost layer of the skin epidermis, acts as an effective bi-directional barrier, preventing water loss (inside-outside barrier) and entry of foreign substances (outside-inside barrier). Although transepidermal water loss (TEWL) is a widely-used measure of barrier function, it represents only inside-outside protection. Therefore, we aimed to establish a non-invasive method for quantitative evaluation of the outside-inside barrier function and visually present a skin barrier model. MATERIALS AND METHODS: Skin barrier damage was induced by applying a closed patch of 1% sodium dodecyl sulfate to the forearms of eight participants; they were instructed to apply a barrier cream on a designated damaged area twice daily for 5 days. The SC barrier was evaluated by measuring TEWL and fluorescein sodium salt penetration rate before, immediately after, and 5 days after damage. The penetration rate was assessed using tape-stripping (TS) technique and fluorescence microscopy. RESULTS: The rates of fluorescein sodium salt penetration into the lower layers of SC differed significantly based on the degree of skin barrier damage. The correlation between penetration rate and TEWL was weak after two rounds of TS and became stronger after subsequent rounds. Five days after skin barrier damage, the penetration rate of all layers differed significantly between areas with and without the barrier cream application. CONCLUSION: Our findings demonstrated that the penetration rate was dependent on skin barrier conditions. The penetration rate and corresponding fluorescence images are suitable quantitative indicators that can visually represent skin barrier conditions.

A robust ultrasensitive transcriptional switch in noisy cellular environments.

Ultrasensitive transcriptional switches enable sharp transitions between transcriptional on and off states and are essential for cells to respond to environmental cues with high fidelity. However, conventional switches, which rely on direct repressor-DNA binding, are extremely noise-sensitive, leading to unintended changes in gene expression. Here, through model simulations and analysis, we discovered that an alternative design combining three indirect transcriptional repression mechanisms, sequestration, blocking, and displacement, can generate a noise-resilient ultrasensitive switch. Although sequestration alone can generate an ultrasensitive switch, it remains sensitive to noise because the unintended transcriptional state induced by noise persists for long periods. However, by jointly utilizing blocking and displacement, these noise-induced transitions can be rapidly restored to the original transcriptional state. Because this transcriptional switch is effective in noisy cellular contexts, it goes beyond previous synthetic transcriptional switches, making it particularly valuable for robust synthetic system design. Our findings also provide insights into the evolution of robust ultrasensitive switches in cells. Specifically, the concurrent use of seemingly redundant indirect repression mechanisms in diverse biological systems appears to be a strategy to achieve noise-resilience of ultrasensitive switches.

Glutathione dynamics is a potential predictive and therapeutic trait for neoadjuvant chemotherapy response in bladder cancer.

Radical cystectomy with preoperative cisplatin-based neoadjuvant chemotherapy (NAC) is the standard care for muscle-invasive bladder cancers (MIBCs). However, the complete response rate to this modality remains relatively low, and current clinicopathologic and molecular classifications are inadequate to predict NAC response in patients with MIBC. Here, we demonstrate that dysregulation of the glutathione (GSH) pathway is fundamental for MIBC NAC resistance. Comprehensive analysis of the multicohort transcriptomes reveals that GSH metabolism and immune-response genes are enriched in NAC-resistant and NAC-sensitive MIBCs, respectively. A machine-learning-based tumor/stroma classifier is applied for high-throughput digitalized immunohistochemistry analysis, finding that GSH dynamics proteins, including glutaminase-1, are associated with NAC resistance. GSH dynamics is activated in cisplatin-resistant MIBC cells, and combination treatment with a GSH dynamics modulator and cisplatin significantly suppresses tumor growth in an orthotopic xenograft animal model. Collectively, these findings demonstrate the predictive and therapeutic values of GSH dynamics in determining the NAC response in MIBCs.

Predictors of manual dexterity at 3 and 6 months after stroke: integration of clinical, neurophysiological, and neuroimaging factors.

This retrospective study aimed to predict dexterity at 3 and 6 months post-stroke by integrating clinical, neurophysiological, and neuroimaging factors. We included 126 patients with first-ever, unilateral, and supratentorial stroke. Demographic, stroke characteristics, and initial clinical assessment variables [Mini-mental state examination and Fugl-Meyer Assessment Upper Extremity (FMA-UE)] were evaluated 2 weeks after stroke. Dexterity, measured using the Manual Function Test (MFT) hand subscore, was the primary outcome. The neurophysiological variables, upper limb somatosensory evoked potential (SEP) and motor evoked potential (MEP), were assessed 2 weeks post-stroke. The neuroimaging variable, fractional anisotropy (FA) of the corticospinal tract (CST), was assessed 3 weeks post-stroke. Multiple regression analysis revealed significant predictors for improved dexterity at 3 and 6 months post-stroke, including younger age, higher FMA-UE score, presence of waveforms in the SEP and MEP, and higher FA values in the CST (adjusted R 2  = 0.776, P  < 0.001 at 3 months; adjusted R 2  = 0.668, P  < 0.001 at 6 months; where MEP, SEP, and FA accounted together for an additional 0.079 and 0.166 of variance beyond age and FMA-UE, respectively). Subgroup analysis was conducted by categorizing the participants based on their initial hand function: those with no hand function (MFT hand subscore = 0) (N = 60) and those with a score >0 (N = 51). Initial FMA-UE was a primary predictive factor regardless of the time point or initial severity, whereas the presence of MEP was a significant predictor only in the group with no initial hand dexterity.

Therapeutic Effect of HDAC5 Binding and Cell Penetrating Peptide for the Treatment of Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is an incurable disease that negatively influences the quality of life of patients. Current and emerging therapies target proinflammatory cytokines and/or receptors to downregulate proinflammatory responses, but insufficient remission requires other therapeutic agents. Herein, we report that the synthetic anti-inflammatory peptide 15 (SAP15) is capable of cell penetration and anti-inflammatory activity in human macrophages. METHODS: SAP15 was labeled with fluorescence and administered to human leukemia monocytic cells (THP-1) cells for cell penetration analysis. Using biolayer interferometry analysis, the binding affinity of SAP15 with histone deacetylase 5 (HDAC5) was measured. SAP15-treated THP-1 cells were analyzed by protein phosphorylation assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). In addition, in vivo analysis of the therapeutic effect on IBD was observed in a dextran sulfate sodium (DSS)-induced model. Samples from SAP15-treated mice were analyzed at both the macroscopic and microscopic levels using ELISA, myeloperoxidase (MPO) assays, and histological evaluations. RESULTS: SAP15 was internalized within the cytosol and nucleus of THP-1 cells and bound to the HDAC5 protein. SAP15-treated macrophages were assessed for protein phosphorylation and showed inhibited phosphorylation of HDAC5 and other immune-related proteins, which led to increased M2-like macrophage markers and decreased M1-like macrophage markers and tumor necrosis factor-α and interleukin-6 cytokine levels. The SAP15 treatment on IBD model showed significant recovery of colon length. Further histological analysis of colon demonstrated the therapeutic effect of SAP15 on mucosal layer. Moreover, proinflammatory cytokine levels and MPO activity from the plasma show that SAP15 is effective in reduced proinflammatory responses. CONCLUSION: These findings suggest that SAP15 is a novel peptide with a novel cell-penetrating peptide with anti-inflammatory property that can be used as a therapeutic agent for IBD and other inflammatory diseases.

Measuring Glutathione Regeneration Capacity in Stem Cells.

Glutathione (GSH) is a chief cellular antioxidant, affecting stem cell functions. The cellular GSH level is dynamically altered by the redox buffering system and transcription factors, including NRF2. Additionally, GSH is differentially regulated in each organelle. We previously reported a protocol for monitoring the real-time GSH levels in live stem cells using the reversible GSH sensor FreSHtracer. However, GSH-based stem cell analysis needs be comprehensive and organelle-specific. Hence, in this study, we demonstrate a detailed protocol to measure the GSH regeneration capacity (GRC) in living stem cells by measuring the intensities of the FreSHtracer and the mitochondrial GSH sensor MitoFreSHtracer using a high-content screening confocal microscope. This protocol typically analyses the GRC in approximately 4 h following the seeding of the cells onto plates. This protocol is simple and quantitative. With some minor modifications, it can be employed flexibly to measure the GRC for the whole-cell area or just the mitochondria in all adherent mammalian stem cells.

Purification and Characterization of Mitochondrial Mg2+-Independent Sphingomyelinase from Rat Brain.

Sphingomyelinase (SMase) catalyzes ceramide production from sphingomyelin. Ceramides are critical in cellular responses such as apoptosis. They enhance mitochondrial outer membrane permeabilization (MOMP) through self-assembly in the mitochondrial outer membrane to form channels that release cytochrome c from intermembrane space (IMS) into the cytosol, triggering caspase-9 activation. However, the SMase involved in MOMP is yet to be identified. Here, we identified a mitochondrial Mg2+-independent SMase (mt-iSMase) from rat brain, which was purified 6,130-fold using a Percoll gradient, pulled down with biotinylated sphingomyelin, and subjected to Mono Q anion exchange. A single peak of mt-iSMase activity was eluted at a molecular mass of approximately 65 kDa using Superose 6 gel filtration. The purified enzyme showed optimal activity at pH of 6.5 and was inhibited by dithiothreitol and Mg2+, Mn2+, N2+, Cu2+, Zn2+, Fe2+, and Fe3+ ions. It was also inhibited by GW4869, which is a non-competitive inhibitor of Mg2+-dependent neutral SMase 2 (encoded by SMPD3), that protects against cytochrome c release-mediated cell death. Subfractionation experiments showed that mt-iSMase localizes in the IMS of the mitochondria, implying that mt-iSMase may play a critical role in generating ceramides for MOMP, cytochrome c release, and apoptosis. These data suggest that the purified enzyme in this study is a novel SMase.

Modulation of lignin biosynthesis for drought tolerance in plants.

Lignin is a complex polymer that is embedded in plant cell walls to provide physical support and water protection. For these reasons, the production of lignin is closely linked with plant adaptation to terrestrial regions. In response to developmental cues and external environmental conditions, plants use an elaborate regulatory network to determine the timing and location of lignin biosynthesis. In this review, we summarize the canonical lignin biosynthetic pathway and transcriptional regulatory network of lignin biosynthesis, consisting of NAC and MYB transcription factors, to explain how plants regulate lignin deposition under drought stress. Moreover, we discuss how the transcriptional network can be applied to the development of drought tolerant plants.

High-glutathione mesenchymal stem cells isolated using the FreSHtracer probe enhance cartilage regeneration in a rabbit chondral defect model.

BACKGROUND: Mesenchymal stem cells (MSCs) are a promising cell source for cartilage regeneration. However, the function of MSC can vary according to cell culture conditions, donor age, and heterogeneity of the MSC population, resulting in unregulated MSC quality control. To overcome these limitations, we previously developed a fluorescent real-time thiol tracer (FreSHtracer) that monitors cellular levels of glutathione (GSH), which are known to be closely associated with stem cell function. In this study, we investigated whether using FreSHtracer could selectively separate high-functioning MSCs based on GSH levels and evaluated the chondrogenic potential of MSCs with high GSH levels to repair cartilage defects in vivo. METHODS: Flow cytometry was conducted on FreSHtracer-loaded MSCs to select cells according to their GSH levels. To determine the function of FreSHtracer-isolated MSCs, mRNA expression, migration, and CFU assays were conducted. The MSCs underwent chondrogenic differentiation, followed by analysis of chondrogenic-related gene expression. For in vivo assessment, MSCs with different cellular GSH levels or cell culture densities were injected in a rabbit chondral defect model, followed by histological analysis of cartilage-regenerated defect sites. RESULTS: FreSHtracer successfully isolated MSCs according to GSH levels. MSCs with high cellular GSH levels showed enhanced MSC function, including stem cell marker mRNA expression, migration, CFU, and oxidant resistance. Regardless of the stem cell tissue source, FreSHtracer selectively isolated MSCs with high GSH levels and high functionality. The in vitro chondrogenic potential was the highest in pellets generated by MSCs with high GSH levels, with increased ECM formation and chondrogenic marker expression. Furthermore, the MSCs' function was dependent on cell culture conditions, with relatively higher cell culture densities resulting in higher GSH levels. In vivo, improved cartilage repair was achieved by articular injection of MSCs with high levels of cellular GSH and MSCs cultured under high-density conditions, as confirmed by Collagen type 2 IHC, Safranin-O staining and O'Driscoll scores showing that more hyaline cartilage was formed on the defects. CONCLUSION: FreSHtracer selectively isolates highly functional MSCs that have enhanced in vitro chondrogenesis and in vivo hyaline cartilage regeneration, which can ultimately overcome the current limitations of MSC therapy.

The first recent case of Cimex hemipterus (Hemiptera: Cimicidae) with super-kdr mutations in the Republic of Korea.

With the increase in international travel and trade, in conjunction with the development of insecticide resistance, infestations of Cimex lectularius (L.) and Cimex hemipterus (F.) (Hemiptera: Cimicidae) have resurged globally in the last 2 decades. Recently, it was reported that C. hemipterus was also found in temperate regions, indicating the possibility of its expansion outside tropical regions. Cimex hemipterus has not been officially recorded in Korea since its initial description in 1934. Here, we report the first recent case of C. hemipterus in Korea based on morphological and molecular identification. Partial sequencing of the voltage-sensitive sodium channel gene revealed super-kdr mutations (M918I and L1014F) that are associated with pyrethroid resistance. This case report serves as a warning to intensify the bed bug surveillance system in Korea regarding the presence of C. hemipterus and to prepare effective alternative insecticides for pyrethroids.

Signaling pathways underlying nitrogen transport and metabolism in plants.

Nitrogen (N) is an essential macronutrient required for plant growth and crop production. However, N in soil is usually insufficient for plant growth. Thus, chemical N fertilizer has been extensively used to increase crop production. Due to negative effects of N rich fertilizer on the environment, improving N usage has been a major issue in the field of plant science to achieve sustainable production of crops. For that reason, many efforts have been made to elucidate how plants regulate N uptake and utilization according to their surrounding habitat over the last 30 years. Here, we provide recent advances focusing on regulation of N uptake, allocation of N by N transporting system, and signaling pathway controlling N responses in plants. [BMB Reports 2023; 56(2): 56-64].

National-scale distribution of strontium isotope ratios in environmental samples from South Korea and its implications for provenance studies.

Successful application and accurate interpretation of strontium (Sr) isotope ratios (87Sr/86Sr) requires underlying information about the large-scale variabilities in their signatures from a variety of environmental samples, which can be correlated with the Sr isotopic signatures of underlying local geology. In this national-scale study, we analyzed 87Sr/86Sr in soil, plants, stream water, and Chinese mystery snail (Cipangopaludina chinensis) shells collected from South Korea to evaluate large-scale spatial variabilities, interpret relationships among isotopic signatures of various sample types, and generate spatial distribution isoscapes reflecting the heterogeneity of isotopic signatures across South Korea. Non-parametric comparisons among environmental samples showed non-significant differences in their isotopic ratios. The 87Sr/86Sr of plant and soil samples were strongly correlated (R2adj = 0.93), suggesting that both reflect national-scale lithological properties. Similarly, the 87Sr/86Sr of shells showed strong correlations with the 87Sr/86Sr of both plant and soil samples (R2adj = 0.90). The 87Sr/86Sr signatures of environmental samples in this study aligned with expected Sr isotopic values and generally reflected local geology. Spatial distribution maps of samples showed similar 87Sr/86Sr spatial patterns, with high radiogenic values from granitic and granitic gneiss rocks systems and low radiogenic values from volcanic and sedimentary rock systems. Stream water samples showed significant correlations with soil and plant isotopic ratios, but with a low coefficient of determination (R2adj = 0.68). The deviations were much larger for samples with 87Sr/86Sr > 0.720. Further study is needed to improve the accuracy of baseline determination and interpretation of stream water isotopic variations.