The lack of tumor-specific targeting remains a major bottleneck in photothermal therapy. Here, we exploit the natural affinity of nicotinamide (NAM) for Ki67, a tumor proliferation marker, to design a targeted photothermal nanomaterial. NAM-derived carbon dots (NAM-CDs) were synthesized via a one-step solvothermal method, in which the carbon core serves as a scaffold for the multivalent presentation of NAM moieties. Dynamic molecular docking simulations revealed that NAM-CDs exhibited a markedly enhanced binding affinity toward Ki67, with binding energy of -7.7 kcal/molcompared with -3.8 kcal/mol for free NAM. These results indicate that the multivalent display of NAM not only preserves but also amplifies its intrinsic Ki67-targeting capability. To further optimize the photophysical properties of NAM-CDs, the synthesis temperature was systematically tuned. At 180 °C, the resulting NAM-CDs developed a pyridine-rich surface characterized by maximized pyrrolic-N content and enhanced amide bond formation, facilitating efficient energy transfer from the carbon core to surface states. This optimized electronic structure synergistically enhanced both red fluorescence emission and photothermal conversion efficiency. The pyridine-rich NAM-CDs exhibited excellent biocompatibility, specific nuclear retention through Ki67-mediated interactions in cancer cells, and potent photothermal tumor ablation upon 660 nm laser irradiation in vivo, achieving complete tumor regression without recurrence over a 30-day observation period. By harnessing the inherent Ki67 affinity of NAM, this work provides a facile strategy for imparting tumor-targeting capability to photothermal agents, opening a new avenue for proliferation-marker-directed cancer therapy.
Although physiological assessment has been used in decision-making for revascularization, its role in predicting the future risk of acute coronary syndrome (ACS) remains underexplored. This study aims to investigate the independent and combined prognostic significance of hemodynamic disease severity and distribution in identifying ACS culprit vessels, in conjunction with lumen and plaque characteristics. The EMERALD-II study is an international, multicenter, internal case-control study enrolling 351 patients with ACS who underwent coronary computed tomography angiography (CTA) 1 month to 3 years before the event. Culprit and nonculprit vessels were identified by matching invasive coronary angiography with coronary CTA findings. High-risk plaque (HRP) characteristics, including minimum lumen area <4 mm2, plaque burden ≥70%, low-attenuation plaque, positive remodeling, spotty calcification, and napkin-ring sign, were assessed by a core laboratory, with HRP defined as ≥3 HRP characteristics. From coronary CTA, the authors derived both the hemodynamic severity of the disease (fractional flow reserve derived from computed tomography [FFRCT]) and its spatial distribution (diffuse vs focal), as assessed by the pullback pressure gradient derived from coronary CTA (PPGCT). Vessels were categorized into 4 hemodynamic disease patterns: nonischemic (FFRCT >0.80), hemodynamic diffuse (FFRCT ≤0.80 and PPGCT ≤0.50), mixed (FFRCT ≤0.80 and 0.50 < PPGCT ≤0.60), and focal disease (FFRCT ≤0.80 and PPGCT >0.60). Among 873 vessels, the mean FFRCT was 0.74 ± 0.17 and the mean PPGCT was 0.54 ± 0.14. Both lower FFRCT and higher PPGCT were independently associated with higher ACS risk (OR per 0.1 increase in FFRCT: 0.71 [95% CI: 0.65-0.77]; P < 0.001; OR per 0.1 increase in PPG: 1.22 [95% CI: 1.09-1.37]; P < 0.001). Among the 4 subgroups of hemodynamic disease pattern, hemodynamic focal disease showed the highest risk of ACS (relative risk [RR]: 2.02 [95% CI: 1.74-2.36]; P < 0.001), myocardial infarction (RR: 1.75 [95% CI: 1.43-2.14]; P < 0.001), and unstable angina (RR: 2.54 [95% CI: 2.00-3.22]; P < 0.001). It remained a predictor for ACS in nonobstructive lesions (OR: 3.56 [95% CI: 1.43-8.84]), obstructive lesions (OR: 3.16 [95% CI: 1.96-5.07]), non-HRP (OR: 6.69 [95% CI: 3.59-12.5]), and HRP (OR: 2.98 [95% CI: 1.83-4.87]). Although the maximal lesion-level ΔFFRCT (differences in FFRCT across the lesion) demonstrated superior model performance compared with models incorporating FFRCT and PPGCT, higher PPGCT was additionally associated with increased ACS risk, particularly among vessels with maximal ΔFFRCT ≥0.10. Hemodynamic disease distribution, as measured by PPGCT, complements FFRCT in predicting ACS risk. The integration of hemodynamic disease patterns provides additional prognostic value beyond lumen and plaque characteristics, with hemodynamic focal disease emerging as an independent predictor and a potential therapeutic target for ACS prevention. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and Computational Fluid Dynamics II [EMERALD II]; NCT03591328).
Rice cultivation is an important source of agricultural methane emissions, and country-level monitoring is needed to evaluate how emission pressure evolves together with rice-sector production and market conditions. This study provides an exploratory dynamic monitoring assessment of methane emissions in Indonesia, the Philippines, and Viet Nam over the period 2000-2023. Annual data from FAOSTAT were used to examine methane emissions, methane emission intensity, rice production indicators, producer prices, and Food CPI. Long-term trends were evaluated using the Mann-Kendall test and Sen's slope estimator. Dynamic associations were assessed using a parsimonious panel vector autoregression, with unit-root and residual-based cointegration diagnostics, first-difference robustness analysis, alternative Cholesky orderings, generalized impulse responses, and residual-bootstrap confidence intervals. The trend results reveal heterogeneous methane-emission trajectories across the three countries. Methane emissions declined significantly in Indonesia, increased significantly in the Philippines, and showed no statistically significant trend in Viet Nam. In contrast, methane emission intensity declined in all three countries, indicating that total emissions and intensity-based performance may move in different directions. The revised PVAR(1) results suggest that methane-emission responses are statistically associated with selected agricultural and price-related innovations, particularly producer-price innovations under the baseline recursive ordering. However, first-difference results show that many responses are concentrated in the short run, and FEVD results are sensitive to identification assumptions. Generalized impulse response-based decomposition indicates that methane-emission variability is primarily own-driven under ordering-invariant assumptions. Overall, the findings support a cautious monitoring interpretation. Rice-sector methane assessment should track both total emissions and emission intensity while considering production scale, harvested area, and dynamic adjustment patterns. The study provides exploratory evidence for three rice-producing countries and highlights the importance of transparent data construction, parsimonious modelling, and robustness checks when using aggregate country-level data to assess methane-emission dynamics.
Implant-associated infections are driven by bacterial biofilm formation and remain difficult to eradicate using conventional antibiotic-based strategies. Here, we present a dynamically actuated reconfigurable topographical surface (DARTS) that integrates intrinsically bactericidal nanoscale surface topography with programmable mechanical actuation to achieve durable, antibiotic-free infection control. Using a scalable bottom-up nanofabrication strategy, we generate tunable wrinkled MXene topographies that exhibit contact-mediated bactericidal activity against both Gram-positive and Gram-negative bacteria without chemical leaching. Integration with a soft robotic actuator enables reversible modulation of surface geometry, which synergistically enhances bacterial removal and killing, resulting in near-complete disruption of mature biofilms. Dynamic actuation further sensitizes released bacteria to antibiotic treatment. In a mouse subcutaneous implant infection model, DARTS with actuation achieves sustained suppression of bacterial burden and markedly improves host tissue outcomes. Remote, noninvasive actuation using near-infrared laser stimulation further highlights the translational potential of this platform for implantable antibacterial applications. Implant infections are difficult to treat because bacteria form biofilms that protect them from antibiotics and the immune system. Current materials often rely on chemical release, which can lose effectiveness over time. Here, we present a new surface that both kills bacteria and removes them. The surface uses nanoscale features to physically damage bacterial cells, while dynamic motion clears attached bacteria and biofilms. This allows continuous, chemical-free control of infection. In a mouse implant model, the system greatly reduced bacterial burden and improved tissue healing. This work introduces a new way to control bacteria using dynamic surface design and could be applied not only to medical implants but also to environmental, food, textile, and marine systems.
Drawing on social identity theory (SIT), this qualitative study examines how AI adoption threatens the professional social identity of content creators in Vietnamese communications agencies and the identity-management strategies they employ in response. Despite research on technological disruption and professional identity in Western contexts, the role of cultural values in moderating identity threat and coping processes remains underexplored, particularly in collectivist Asian societies, where group membership rather than individual competence constitutes the primary source of self-concept. Through semi-structured interviews with 25 content creators across communications agencies in Hanoi and Ho Chi Minh City, we identified four forms of identity threat: competence threat, distinctiveness threat, categorization threat, and value threat. The findings reveal that Vietnamese content creators predominantly employ collective identity redefinition rather than individual repositioning or direct resistance, reflecting Vietnam's collectivist cultural orientation, high power distance, and face concerns. Participants reframed AI as a tool that enables a focus on strategic and culturally nuanced work, particularly Vietnamese cultural understanding, while delegating mechanical tasks, thereby preserving professional group distinctiveness through shared narratives rather than individual competitive positioning. This study demonstrates that cultural context fundamentally moderates the forms of identity threat that prove most salient and the coping strategies that are employed, contributing to cross-cultural organizational psychology and challenging Western-centric assumptions about professional identity transformation during technological disruption. Practically, the findings suggest that Western change management approaches emphasizing individual adaptation may prove ineffective in collectivist cultures, necessitating culturally responsive AI integration strategies that facilitate collective sense-making rather than mandating individual skill development.
Coronavirus (CoV) infections continue to pose a significant challenge to global public health and food security. The COVID-19 pandemic has underscored the importance of One Health approaches and improved surveillance systems. This is due to the considerable potential of CoVs to infect a broad spectrum of hosts and cause respiratory diseases. The present study investigated CoVs circulating in livestock in northern Vietnam using molecular detection and phylogenetic analysis. A total of 412 samples collected from livestock were analysed for the presence of CoVs, and we detected infectious bronchitis virus (IBV), porcine haemagglutinating encephalomyelitis virus (PHEV), and avian Gamma-CoV. Nearly full-length genomes of IBV and PHEV were obtained in this study. Phylogenetic analysis inferred that the IBV strains detected in this study were GI-13 vaccine-like strains. Furthermore, this study provides the first genome sequences of Vietnamese PHEV strains. The viruses were closely related to the respiratory-variant lineage detected in China, suggesting that the viruses may have entered Vietnam from China; however, further analysis of PHEVs would likely be necessary for a more detailed characterization. Moreover, avian Gamma-CoVs were inferred to be related to migratory birds, thereby suggesting the risk of transmission from migratory birds to livestock. In summary, this study provides insights into the diversity of CoVs in livestock in northern Vietnam. Therefore, continuous surveillance is necessary to prevent further spread of CoVs among livestock.
Employer feedback is widely recognized as an important mechanism for evaluating graduate outcome quality in higher education, particularly in the health sciences. However, empirical evidence on employer satisfaction with undergraduate Bachelor of Pharmacy (BPharm) graduates in developing countries, including Vietnam, remains limited. This study examined factors influencing employer satisfaction with BPharm graduates from Thanh Do University. A cross-sectional study was conducted among 127 employers from September 2025 to March 2026. The questionnaire consisted of 17 observed variables developed based on the Vietnam National Qualifications Framework, the Vietnamese Pharmacist Competency Standards, and the learning outcomes of the pharmacy program at Thanh Do University. Data were analyzed using Cronbach's alpha, exploratory factor analysis (EFA), and multiple linear regression. The analysis identified two factors: (1) Knowledge and Skills (KS) (β = 0.597) and (2) Autonomy and Responsibility (AR) (β = 0.429). Both factors were positively associated with employer satisfaction and jointly explained 59.2% of the variance in overall satisfaction. The mean satisfaction score was 3.76/5, indicating generally positive evaluations, although gaps remained in higher-order competencies. No significant difference in satisfaction was observed between public and private sector employers (p > 0.05). Although overall employer satisfaction was favorable, gaps persist in graduates' practical application competencies. The findings indicate the need for competency-based curriculum reform and stronger alignment with labor market demands.
Developmental and reproductive toxicity (DART) assessment is essential for product safety evaluation but relies heavily on vertebrate models that are costly, time consuming, and resource intensive. Although Caenorhabditis elegans has emerged as a promising new approach methodology (NAM) for rapid, cost-effective, whole-organism toxicology, broader adoption has been limited by the lack of high-resolution, rapid imaging approaches, limited endpoints, and insufficient evidence supporting assay robustness. To overcome these limitations, we developed vivoDART, a multiparametric imaging-based DART assay designed to be accurate, efficient, robust, and sensitive. Building on our machine learning-accelerated developmental toxicity platform, vivoDART uses microfluidic-assisted, high-resolution brightfield imaging to quantify six developmental and reproductive endpoints for comprehensive DART analysis. Developmental endpoints are derived from automated body-dimension analysis, whereas reproductive endpoints are obtained by quantifying total in utero embryo number and classifying embryos as early- or late-stage relative to the twofold stage. The assay directly assesses sublethal DART phenotypes while minimizing reliance on non-specific apical endpoints such as lethality. vivoDART demonstrated high repeatability, with mean coefficients of variation of 1-5% for developmental endpoints and 6-17% for reproductive endpoints, supporting high statistical power. Assay validation performed using DMSO, methylmercury, and propiconazole involved phenotyping ~ 400,000 embryos across ~ 9,200 worms. Densely sampled concentration-response curves enabled ECx prediction with narrow confidence intervals and captured subtle to strong effects across a broad dynamic range of 1.0-237 µM. Notably, late-stage embryo number was the most sensitive endpoint among the chemicals tested, preceding changes in total embryo number, body size, or viability. These findings indicate that the observed responses reflected DART-specific effects rather than non-specific lethality. These results establish vivoDART as a sensitive, repeatable, and scalable whole-organism platform for rapid, cost-effective chemical prioritization and comparative hazard assessment.
This study investigated the inhibitory potential of selected phytochemicals and conventional drugs against gastric H⁺/K⁺-ATPase, an important therapeutic target associated with acid-related gastrointestinal disorders such as peptic ulcers and gastroesophageal reflux disease. Computational approaches, including molecular docking, molecular dynamics simulations, MMGBSA free energy calculations, and ADMET profiling, were employed to evaluate the pharmacological relevance of the selected compounds. Molecular docking analysis revealed that several compounds exhibited favorable interactions with the target enzyme, with ciprofloxacin demonstrating stronger binding affinity than 3-hydroxypropyl oleate in both active-site and blind docking studies. Interaction analyses further showed that ciprofloxacin formed stable hydrogen bonds, hydrophobic interactions, and attractive charge interactions within the enzyme binding pocket. Molecular dynamics simulations confirmed the superior structural stability of the ciprofloxacin-protein complex through lower RMSD, RMSF, RoG, and SASA values compared with 3-hydroxypropyl oleate. Although MMGBSA calculations indicated slightly stronger total binding free energy for 3-hydroxypropyl oleate, ciprofloxacin displayed better overall compactness and interaction stability throughout the simulation period. ADMET and pharmoglyph analyses further established ciprofloxacin as the more promising candidate due to its favorable drug-likeness, high gastrointestinal absorption, acceptable solubility, lower metabolic risks, and excellent PharmoScore. The integrated computational findings suggest that ciprofloxacin possesses significant inhibitory potential against gastric H⁺/K⁺-ATPase and may serve as a promising scaffold for the development of safer and more effective anti-ulcer therapies.
Species of the genus Poteriospumella are reported for the first time in Vietnam and the tropical region. The investigations were conducted in the freshwaters of Vietnam using the culture method and high-throughput sequencing (V9-ITS1 rDNA metabarcoding). Fifteen cultures of Poteriospumella vasocystis were isolated from 8 water bodies in 3 provinces. Metabarcoding studies revealed 4 additional localities of this species. Additionally, two other known species of the genus Poteriospumella were revealed by the metabarcoding: P. lacustris in 19 localities and P. maldiviensis in 8 habitats. The paper discusses the distribution patterns of the detected species and the potential diversity of the genus in different climatic zones.
Lichens are widely used as bioindicators of air pollution. This study aims to evaluate the accumulation of potentially toxic elements in lichens Usnea articulata (L.) Hoffm to assess atmospheric pollution in Hai Phong city, Vietnam. The content of Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, P, Pb, S, Sr, V, Zn, and Hg in exposed and unexposed lichen samples was determined using Inductively Coupled Plasma-Optical Emission Spectrometry and a direct mercury analyzer. Analysis data showed that mean content of all elements, except Hg and S, was higher in exposed lichens. High levels of Zn, Al, Mn, Fe, V, and Ni were found in samples exposed near industrial zones. The Relative Accumulation Factor revealed lichens enrichment in Al, Co, Mn, Fe, and V, as well as a depletion of Hg and S. Correlation and principal component analyses identified the predominant sources of elements deposition as industrial activity, coal combustion, and transport activity. Based on contamination factor values, the level of air pollution in Hai Phong can be classified as suspected with low ecological risk index values. Additionally, the assessment of exposure to potentially toxic elements through inhalation, ingestion, and dermal contact allowed determination of the hazard index values, which did not exceed unit at any exposure sites. For future research, long-term or multi-seasonal biomonitoring studies should be conducted in this area.
Pediatric duodenal injury is uncommon, often presents with non-specific features, and is frequently recognized late. To describe injury patterns, diagnostic imaging, operative strategies (including decompression approaches), and outcomes in children with blunt duodenal injuries. We conducted a retrospective study of consecutive patients aged ≤18 years with blunt abdominal trauma and confirmed duodenal injury treated at a tertiary pediatric hospital in Vietnam (October 2015-May 2024). Demographics, injury characteristics (American Association for the Surgery of Trauma [AAST] grade), imaging findings, management (non-operative vs. operative), decompression approaches, complications, and length of stay (LOS) were extracted from medical records and summarized descriptively. Fourteen patients were included (mean age 8.8 years). AAST grades I-IV were [3/14 (21.4%)], [6/14 (42.9%)], [4/14 (28.6%)], and [1/14 (7.1%)], respectively. Computed tomography (available in 10/14) frequently demonstrated free intraperitoneal fluid ([10/10, 100%]) and, less commonly, duodenal wall discontinuity ([2/10, 20%]). Non-operative management was used in hematoma-dominant injuries ([3/14, 21.4%]). Surgery was performed in [11/14, 78.6%], most commonly primary repair ([6/11]) or Roux-en-Y duodenojejunostomy ([2/11]). Systematic decompression was applied in all cases: nasogastric tube alone (6/14), nasogastric plus feeding jejunostomy (4/14), nasogastric plus retrograde jejunostomy (1/14), or triple-tube decompression (3/14). Postoperative complications occurred in 7/11 (63.6%, 95% CI: 30.8-89.1%) of surgically managed patients; there were no deaths. Median hospital LOS was 27 days (range 3-92). Pediatric blunt duodenal injury should be suspected in children with non-specific abdominal symptoms after blunt trauma. In this series, CT-based assessment and tailored management with decompression were feasible and associated with recovery in all patients.
The objective of this investigation is to identify and enhance compounds from the medicinal plant Erythrina variegata L. that possess potential inhibitory activity against acetylcholinesterase (AChE). Consequently, this investigation will contribute to the pursuit of supportive therapeutic agents for Alzheimer's disease. The initial research matrix was composed of nanocluster materials that were derived from the crude extract. The identification of 13 compounds was achieved by utilizing an ultraperformance liquid chromatography system in conjunction with quadrupole time-of-flight mass spectrometry for structural elucidation. Compound VN62 was chosen due to its favorable binding energy (ES = -8.038 kcal/mol) and RMSD = 1.388 Å, as evidenced by molecular docking simulations and analytical results with the AChE protein (PDB ID: 1EVE). The pIC50 values were predicted using reliable QSAR models, such as QSARGA‑MLR, QSARGA‑ANN, and QSARKPLS‑LF, which were constructed on this basis. Five novel derivatives (VN62N1-VN62N5) were designed from VN62, subsequently semisynthesized, and structurally confirmed using spectroscopic methods, guided by QSAR and docking results. The AChE inhibitory activity was assessed in vitro, and VN62 demonstrated an IC50 of 1.34 μg/mL (pIC50 = 5.498). Conversely, the newly designed derivatives demonstrated a trend toward enhanced activity. Furthermore, a multicriteria evaluation model integrating QSAR, docking, ADMET, and quantum descriptors identified VN62N4 as the top-ranked candidate overall. Molecular dynamics simulations over 400 ns confirmed the structural stability of the VN62N4-AChE complex, as evidenced by stable RMSD, low RMSF in active-site residues, and persistent hydrogen bonding and hydrophobic interactions. The findings verify the efficacy of a comprehensive, multimethod in silico screening strategy in directing the development of AChE inhibitors.
Urethral stricture is a rare condition in women that presents challenges for reconstructive surgery. Urethroplasty can be particularly difficult for these patients, especially in developing countries, due to limited infrastructure and concerns about recurrence. In this report, we present a case involving a 60-year-old woman who experienced long-standing urinary difficulties and had a history of multiple urethral dilations. The diagnosis was confirmed via voiding cystourethrogram, retrograde urethrogram, and cystoscopy. The patient underwent urethral reconstruction using an oral mucosa graft to create a dorsal surface for the urethra. Four months after surgery, she had normal urinary function, with uroflowmetry showing a maximum flow rate (Qmax) exceeding 15 mL/s and no signs of postoperative incontinence. For a female with a urethral stricture, studies indicate that urethroplasty, particularly using a dorsal onlay buccal mucosa graft, is the gold standard for treatment. However, there are relatively few cases utilizing this technique due to concerns about recurrence risk and its complexity. The results highlight the effectiveness and long-term success of buccal mucosa graft urethroplasty, especially in challenging cases of urethral stricture that are difficult to treat using traditional methods. Dorsal onlay oral mucosa graft urethroplasty is an effective and viable option for treating female urethral stricture, especially when performed by an experienced surgeon. However, further studies with larger sample sizes and longer follow-up are needed to confirm the long-term efficacy and safety of oral mucosal grafts for urethral reconstruction in females.
Coccidiosis has resulted in substantial economic losses in the poultry industry. The prevalence and severity of drug resistance to anticoccidial agents have exacerbated the challenges associated with controlling coccidiosis. Consequently, exploring novel drug targets is crucial for the prevention and treatment of coccidiosis. In this study, we performed acetylation modification proteomics on the sporozoites and merozoites of Eimeria tenella during the asexual stage. Moreover, the anticoccidial efficacy of histone deacetylase (HDAC) inhibitors was evaluated both in vitro and in vivo. In total, 341 differentially acetylated proteins and 558 differentially acetylated modification sites were identified. Histones H2A, H2B, H2B variants, H3, and H4 are all acetylated and have multiple acetylation sites, suggesting that acetylation plays important roles in the gene regulation, replication, and development of E. tenella. KEGG pathway analysis revealed that glycolysis/gluconeogenesis pathway was enriched. Glycolysis is the main mode of energy metabolism in Apicomplexa. In the glycolysis pathway, eight key enzymes are downregulated by acetylation and have multiple acetylation sites. It has been suggested that histone deacetylase (HDAC) is the target of anticoccidial action. Trichostatin A (TSA, an inhibitor of HDAC family deacetylases) and nicotinamide (NAM, an inhibitor of SIRT family deacetylases) can inhibit sporozoite invasion (P ≤ 0.01) and promote sporozoite apoptosis (P ≤ 0.05). Intraperitoneal injection of TSA and NAM can reduce chicken caecal lesions and oocyst shedding, and the anticoccidial index can reach 143. This study is the first to investigate the anticoccidial effect of deacetylase inhibitors, providing a new strategy for the prevention and control of coccidiosis.
Predicting metabolism-dependent drug toxicity encompassing both the bioactivation and detoxification processes remains a critical challenge in preclinical safety evaluations. Conventional cardiomyocyte-only assays frequently misclassify compounds such as terfenadine, which require hepatic metabolism to attenuate cardiotoxicity. Current microphysiological systems (MPS) have practical limitations, such as insufficient hepatocyte oxygenation and complex external fluidic setups. We developed a liver-heart co-culture system that integrates three-dimensional human iPS cell-derived engineered heart tissues (hiPSC-EHTs) and cryopreserved primary human hepatocytes (PHHs), using a modified BioStellar™ Plate-a tubeless, stirrer-pump-integrated microfluidic device customized with an oxygen-permeable membrane. Using this system, we evaluated the cardiotoxicity of terfenadine in hiPSC-EHT monocultures and liver-heart co-cultures. Terfenadine exposure induced marked contractile dysfunction in hiPSC-EHT monocultures, whereas co-culturing with PHHs significantly attenuated this effect. Functional monitoring revealed time- and dose-dependent recovery, consistent with a largely reversible pharmacological mechanism. Drug concentration analysis by LC-MS/MS showed a marked increase in the formation of the primary metabolite fexofenadine, in the co-culture system, which was consistent with the reduced cardiotoxic potential of this metabolite. Gene expression analysis confirmed the presence of hepatic CYP3A4, which supports its predominant role in metabolic detoxification. This study demonstrated that a tubeless, stirrer-pump-integrated system with sustained hepatocyte function enables time-resolved evaluation of pharmacokinetic-pharmacodynamic relationships of metabolism-dependent cardiotoxicity on a single platform. This proof-of-concept approach suggests a potential improvement in the translational predictability of human-relevant, metabolism-dependent cardiotoxicity by enabling integrated evaluation of pharmacokinetic and pharmacodynamic responses. These findings highlight the utility of this system as a simple and scalable alternative to conventional perfusion-based MPS.
Drought imposes one of the most damaging constraints on maize productivity, particularly during critical developmental period such as flowering and pollination, when water deficit most severely disrupts normal plant growth. The Bcl-2-associated athanogene (BAG) proteins constitute a highly conserved co-chaperone family whose members participate in extensive biological processes, ranging from developmental regulation to adaptive responses under abiotic stress. In the present study, a comprehensive genome-wide characterization of the maize (Zea mays L.) reference genome (Zm-B73-REFERENCE-NAM-4.0) identified 24 ZmBAG genes, named ZmBAG1-24, which were classified into seven distinct phylogenetic groups. All identified proteins share a conserved BAG domain, while subsets additionally carry either a ubiquitin-like (UBL) domain or a plant-specific isoleucine-glutamine (IQ) calmodulin-binding motif positioned toward the N-terminus. Promoter analysis of ZmBAGs uncovered an abundance of stress-responsive regulatory elements were present, pointing to this gene family in ABA-mediated and drought-responsive transcriptional programs. Further transcriptional profiling under drought-stress conditions revealed divergent expression characteristics among family members, indicating that individual ZmBAGs contribute differentially to the drought stress. Among them, ZmBAG14 showed lower expression under drought stress, compared to the control (well-watered). Functional characterization using bag14 EMS mutants demonstrated that diminished ZmBAG14 expression correlated with reduced reactive oxygen species (ROS) accumulation in stomatal guard cells and water loss rate, elevated activities of peroxidase (POD) and superoxide dismutase (SOD), and ultimately enhanced drought tolerance and yield improvements. Protein interaction studies further revealed that ZmBAG14 interacts with the inward-rectifying potassium channel ZmKZM2, which influences stomatal movement by modulating K+ influx in guard cells under drought stress. Together, these findings provide a new perspective for genome-wide identification and functional utilizing of ZmBAG genes to improve drought tolerance in maize.
This study examines the mechanisms underlying the influence of minimalism on ethically minded consumer behavior. Within the Stimulus-Organism-Response framework and Self-Determination Theory, the study investigates the effect of minimalism on ethically minded consumer behavior through moral identity (internalization and symbolization) and psychological well-being, with attention paid to the moderating effect of eco-anxiety. Data for this study came from a survey involving 555 young consumers in Vietnam and were analyzed using partial least squares structural equation modeling. It is demonstrated that minimalist lifestyle orientation positively impacts psychological well-being and both aspects of moral identity. Moral identity symbolization and well-being were found to have a direct and positive effect on ethically minded consumer behavior, but moral identity internalization did not have such a direct influence. Instead, moral identity internalization positively affects moral identity symbolization. Furthermore, psychological well-being is identified as an important psychological mechanism underlying the relationship between minimalist lifestyle orientation and ethical decision making. This study emphasizes the importance of self-concept and well-being for ethical decision-making. It demonstrates that eco-anxiety selectively moderates the internal identity process, intensifying the conversion of moral identity internalization into symbolization while exerting no significant moderating influence on the final behavioral outcome via the relationship between moral identity symbolization and ethically minded consumer behavior.
Environmental risk assessment (ERA) has not yet undergone the shift toward new approach methodologies (NAMs), that has reshaped human health safety assessment. This study adapts the 10-step read across next generation risk assessment (NGRA) framework developed for cosmetic safety, to the environmental domain and applies it to triclosan (TCS), given its data richness and environmental relevance. The framework consists of three tiers: Tier 0 for problem formulation and in silico screening; Tier 1 for bioavailability estimation and mode of action hypothesis formulation; and Tier 2 for refinement, hazard characterisation, risk quantification and uncertainty assessment. Four core principles are proposed for environmental NGRA: the assessments should (1) be exposure-anchored, (2) be mechanism-based, (3) have translatable thresholds, and (4) be both protective and transparent. Exposure was assessed using a two-tier use-based predicted environmental concentration (PEC) approach. The lower tier applied a conservative aggregate cosmetic exposure scenario, yielding a screening PEC of 0.74 µg/L. This value exceeded both the ecological threshold of toxicological concern (ecoTTC) and Tier 0 read across thresholds, triggering refinement using year specific exposure data. Integrated bioactivity, QIVIVE and conservation analysis identified lipid and steroid metabolism as the most sensitive pathways. Tier 2 yielded two NGRA predicted no effect concentrations (PNECs): a species sensitivity distribution (SSD)-based PNEC of 0.020 µg/L and a lowest environmental point of departure (ePoD)-based PNEC of 0.007 µg/L. Risk characterisation ratios (RCRs) were below 1 from 2019 onwards under both routes, supporting an environmental NGRA approach at least as protective as conventional ERA. While the proposed framework has been demonstrated for an insecticide, this study extends it to a cosmetic ingredient, broadening the transferability of the 10-step framework for NAM-based ERA.
Several common variants have been identified in SCN5A, which encodes the cardiac sodium channel α-subunit Nav1.5 and is targeted by class I antiarrhythmics. Lidocaine and its analog mexiletine both have a primary amine that blocks Na+ current. While lidocaine is highly effective in terminating ventricular tachycardia after acute myocardial infarction, mexiletine has been shown to prevent arrhythmia induction in only ~20% of patients. The factors underlying this inconsistent drug response are unclear. Here, we use cardiomyocytes that are derived from induced pluripotent stem cells to observe that a common polymorphism in the SCN5A gene, S1103Y, exhibits an altered pharmacological response to mexiletine, with enhanced use-dependent and tonic block of peak sodium current. In addition, an unexpected increase in late sodium current causes action potential prolongation. This paradoxical proarrhythmic phenotype shifts the paradigm of conventional anti-arrhythmic therapy with mexiletine, suggesting that background variants may alter pharmacological responses leading to unanticipated consequences. Our results suggest that the unique genetic background of patients should inform therapeutic approaches to treat and prevent arrhythmias associated with common cardiac pathologies. This work exemplifies a New Approach Methodology (NAM) framework for cardiac pharmacology, replacing population-averaged drug testing with a patient-derived, genotype-informed in vitro platform capable of prospectively identifying adverse drug-genotype interactions.