Magnetic reconnection, a universal process governing energy release in astrophysical plasmas, has long been studied as a key phenomenon in magnetized planets. However, its drivers and impacts in unmagnetized bodies remain poorly understood. Despite the detection of magnetic reconnection in the near Venusian magnetotail over a decade ago, the physical mechanism enabling this process in a non-intrinsic magnetic field environment has remained unresolved. Here, we present a global magnetohydrodynamic simulation of Venusian magnetotail reconnection, providing a plausible explanation for this phenomenon. We demonstrate that reconnection is triggered by the compression of the draped interplanetary magnetic field following an interplanetary shock, a mechanism previously associated with terrestrial dynamics. Our results reproduce characteristic reconnection signatures at approximately 1.72 Venus radii down the tail and delineate the formation of three-dimensional magnetic structures consistent with reconnection topologies. These findings highlight a physically plausible pathway by which dynamic pressure enhancement associated with an interplanetary shock may trigger magnetotail reconnection in unmagnetized plasma environments. While based on a single case, these results may provide a physical basis for understanding potential drivers of atmospheric evolution on rocky planets and exoplanets.
The bioluminescent fish Parapriacanthus ransonneti does not synthesize the luciferase enzyme required for light emission; instead, it acquires the high-molecular-weight enzyme from its prey, the ostracod Cypridina noctiluca. This unique phenomenon, termed "kleptoprotein", represents a novel mode of phenotype acquisition where exogenous biopolymers are functionally sequestered. Unlike complex organelle sequestration (e.g., kleptoplasty), the kleptoprotein system involves a single protein, offering a tractable model to elucidate the molecular mechanisms of exogenous protein uptake. However, the mechanisms underlying luciferase internalization remain unknown due to the lack of tools to visualize and quantify this process. Here, we developed a dual-function probe by fusing the fluorescent protein Venus to C. noctiluca luciferase (VCL). Guided by AlphaFold 3 structural simulations predicting stable binding and catalytic integrity, we engineered a membrane-tethered Venus-trap system to validate VCL as a tracer. We demonstrate that VCL specifically interacts with the surface-displayed nanobody. Fluorescence imaging visualized VCL binding at trap-plasmid concentrations ≥ 50 ng/mL and VCL concentrations ≥ 2000 ng/mL. The bioluminescence assay exhibited superior sensitivity, detecting binding at VCL concentrations as low as 200 ng/mL. These results confirm that the fusion protein remains functionally intact and offers a highly sensitive detection method. This VCL-trap system establishes a robust platform for identifying the putative luciferase receptor and dissecting the intracellular dynamics of kleptoprotein bioluminescence.
Among carnivorous plants, the Venus flytrap (Dionaea muscipula) is known for its rapid (<1 s) trap closure. Although buckling instability, hydrostatic pressure, and hydroelastic coupling have all been proposed to be involved, the nature of this process and the relationship between trap size and curvature remain elusive. Here, we monitored the closure of Venus flytraps and performed micro-CT scanning and 3D reconstruction, revealing that increasing angular velocity was correlated with higher values of a non-dimensional shape index. Based on these experimental data, we constructed a geometric model of the trap that takes leaf orientation into account. We found that leaf curvature is dependent on leaf size, a relationship we denote as a size-curvature constraint. We further propose a curvature design derived from differential deformations of a two-layer model of the leaf, which could be a powerful tool to control the curvatures of soft and bending surface structures in the field of biomimetics.
Chronic severe pulmonary regurgitation following repair of right ventricular outflow dysfunction may result in progressive right ventricular dilatation, heart failure, and arrhythmias. In patients with a complex surgical history, particularly those with mechanical tricuspid valve prostheses, standard transvenous access for pulmonary valve implantation can be technically challenging and carries risks for prosthetic valve injury. We report a successful hybrid perventricular Venus P-Valve implantation via left mini-thoracotomy in a 29-year-old man with 2 prior cardiac surgeries, mechanical mitral and tricuspid valves. The procedure was performed on the beating heart without cardiopulmonary bypass, avoiding the risks of a third open-heart surgery. This case highlights the advantages of a hybrid perventricular pulmonary valve implantation strategy in patients with a mechanical tricuspid valve. Hybrid perventricular access can expand transcatheter self-expanding pulmonary valve options in selected high-risk redo patients with a mechanical tricuspid valve and enlarged right ventricular outflow tract.
Short peripheral cannula (SPC)-related phlebitis occurs in 7.5% of critically ill patients, and mechanical irritation from cannula materials is a risk factor. Softer polyurethane cannulas reportedly reduce phlebitis, but the incidence of phlebitis may vary depending on the type of polyurethane. Differences in cannula stiffness may also affect the incidence of phlebitis; however, this relationship is not well understood. This study analyzed intensive care unit (ICU) patient data to compare the incidence of phlebitis across different cannula products, focusing on polyurethane. This is a post-hoc analysis of the AMOR-VENUS study that involved 23 ICUs in Japan. We included patients aged ≥ 18 years, who were admitted to the ICU with SPCs. The primary outcome was phlebitis, evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs). Based on the market share and differences in synthesis, polyurethanes were categorized into PEU-Vialon® (BD, USA), SuperCath® (Medikit, Japan), and other polyurethanes; non-polyurethane materials were also analyzed. Multivariable marginal Cox regression analysis was performed using other polyurethanes as a reference. In total, 1,355 patients and 3,429 SPCs were evaluated. Among polyurethane cannulas, 1,087 (33.5%) were PEU-Vialon®, 702 (21.6%) were SuperCath®, and 276 (8.5%) were other polyurethanes. Among non-polyurethane cannulas, 1,292 (39.8%) were ethylene tetrafluoroethylene (ETFE) cannulas, and 72 (2.2%) used other materials. The highest incidence of phlebitis was observed with SuperCath® (13.1%). Multivariate analysis revealed an HR of 1.45 (95% CI 0.75-2.8, p = 0.21) for PEU-Vialon®, 2.60 (95% CI 1.35-5.00, p < 0.01) for SuperCath®, 2.29 (95% CI 1.19-4.42, p = 0.01) for ETFE, and 2.2 (95% CI 0.46-10.59, p = 0.32) for others. The incidence of phlebitis varied among polyurethane cannulas. Further research is warranted to determine the causes of these differences.
Cytotoxic edema (CE) is a radiographic marker of early tissue injury in cerebral venous thrombosis (CVT) associated with poor outcomes, yet its mechanistic pathway remains unclear. We investigated whether intraparenchymal hemorrhage (IPH) mediates the association between CE and outcomes. We conducted a retrospective cohort study using the multicenter CLOT-VENUS registry, including acute CVT patients treated at two Comprehensive Stroke Centers in the USA and Mexico (2004-2024). CE was defined as hyperintensities around IPH or venous infarct with DWI restricted diffusion and corresponding low ADC, confirming true restricted diffusion. IPH was defined as hemorrhagic transformation of venous infarction or intracerebral hemorrhage on GRE MRI and/or NCCT. Mediation analyses assessed whether IPH mediated CE associations with in-hospital mortality and functional outcomes. Among 394 patients (mean age 42.7 years; 65.5% female), 128 (32.5%) demonstrated CE and 111(30.2%) IPH. CE was associated with in-hospital mortality (aOR 2.63, 95% CI 1.01-7.12) and poor 6-month mRS (aOR 1.71, 95% CI 1.06-2.74). CE was associated with IPH, which in turn was associated with mortality (aOR 8.73, 95% CI 2.93-30.45) and poor mRS (aOR 1.96, 95% CI 1.18-3.25). Adjustment for IPH rendered the CE-outcome associations non-significant. IPH accounted for 76.8% of CE's effect on mortality and 83.8% on 6-month mRS. Our findings suggest that IPH likely mediates the effect of CE on outcomes in CVT. Although the temporal sequence could not be confirmed, the results underscore the value of early CE detection for timely intervention.
Inflammatory serum biomarkers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), are associated with outcomes in acute cerebrovascular diseases. However, their prognostic role in cerebral venous thrombosis remains uncertain. We aimed to assess the prognostic value of these biomarkers in acute cerebral venous thrombosis by identifying optimal thresholds and internally validating their predictive performance. This retrospective observational cohort study included adults diagnosed with acute cerebral venous thrombosis from the international CLOT-VENUS registry (Collaboration on Cerebral Venous Thrombosis Study; 2004-2024), including 2 comprehensive stroke centers in the United States and Mexico. Biomarkers of interest (NLR, MLR, PLR, SII) were calculated from admission complete blood counts. The primary outcome was functional status at 6 months, measured by the modified Rankin Scale dichotomized as 0 to 2 versus 3 to 6. Secondary outcomes included modified Rankin Scale score at discharge and mortality. Associations were tested with multivariable logistic regression adjusted for clinically relevant covariates. Optimal biomarker cutoffs were identified using stratified bootstrap receiver operating characteristic analysis and internally validated with out-of-bag testing. Of 432 patients, 394 met the inclusion criteria, and complete data were available for 339 of those patients. Median age was 40 years [interquartile range, 27-45], and 65.2% were female. Elevated biomarkers at admission were associated with modified Rankin Scale score 3 to 6 at discharge and 6 months. At 6 months, optimal cutoff values for NLR ≥4.88 (adjusted odds ratio [aOR], 2.19; P=0.044), MLR ≥0.54 (aOR, 2.32; P=0.027), PLR ≥161.04 (aOR, 3.33; P=0.003), and SII ≥1388.58 (aOR, 2.03; P=0.049). Similar associations occurred at discharge using the same thresholds. PLR and SII notably predicted mortality at discharge (PLR aOR, 6.33; P=0.008, and SII aOR, 3.93; P=0.031) and at 6 months (PLR aOR, 7.19; P=0.004, and SII aOR, 4.69; P=0.010). Elevated admission levels of NLR, PLR, MLR, and SII are independently associated with poor discharge and 6-month outcomes in patients with acute cerebral venous thrombosis. These accessible biomarkers may aid early risk stratification. Further studies should validate and explore its usefulness in clinical models for personalized management.
Severe aortic stenosis (AS) leads to chronic pressure overload of the left ventricle (LV). We explored the prognostic value of preoperative left ventricular end-diastolic dimension (LVEDD) dilation in patients with severe AS. This is a retrospective study of 108 patients with severe AS who underwent transcatheter aortic valve implantation with the Venus-A valve. These participants were assigned to the large LVEDD and non-large LVEDD groups. The receiver operating characteristic and Kaplan-Meier curves were generated to assess the predictive value of preoperative LVEDD dilation for poor patient prognosis (readmission or death within 1 year postoperatively), as well as its effects on the readmission risk owing to heart failure, and complications and survival rates within 1 year postoperatively. Significant differences were observed between the two groups in B-type natriuretic peptide, creatinine, aortic valve area, transfemoral access, aortic valve peak velocity, mean transvalvular pressure gradient, LVEDD, left ventricular end-systolic dimension, left atrial dimension, interventricular septal thickness, relative wall thickness, left ventricular mass index, left ventricular ejection fraction, E/A ratio, E/e' ratio, and stroke volume index. Preoperative LVEDD dilation showed a predictive value for poor patient prognosis (AUC = 0.843; 95%CI: 0.761-0.906, 50.9 mm cut-off value, 99.9% sensitivity, 62.07% specificity). Preoperative LVEDD dilation was an independent influencing factor for poor prognosis within 1 year postoperatively, associated with increased readmission risk and reduced patient survival rate. Preoperative LVEDD dilation is an independent influencing factor for poor postoperative prognosis in patients. It helps predict poor prognosis within 1 year postoperatively.
Despite similarities in size and density to Earth, Venus followed a radically different evolution, becoming a hot, dry world. Here we review key properties of the planet and discuss how forthcoming missions may explain its puzzling evolutionary history.
The heterodimeric human sweet taste receptor TAS1R2/TAS1R3 is a class C G-protein-coupled receptor responsible for detecting a wide range of sweet-tasting compounds. The Venus flytrap domain of hTAS1R2 (hTAS1R2-VFT) constitutes the main binding site for natural sugars and some noncaloric sweeteners, including sucralose, neotame, and acesulfame-K. However, its biophysical characterization has been limited by difficulties in producing soluble and functional protein, with most strategies relying on refolding from inclusions bodies. In this study, we report the successful expression of soluble, folded, and functional hTAS1R2-VFT using Escherichia coli and a N-terminal small ubiquitin-like modifier (SUMO) fusion protein, avoiding protein refolding from inclusion bodies. A two-step purification process (immobilized metal ion affinity chromatography followed by preparative gel filtration) yielded approximately 0.42 mg of pure protein per liter of culture. Circular dichroism spectroscopy and size-exclusion chromatography coupled with multiangle static light scattering analysis confirmed proper folding and monomeric behavior of SUMO-hTAS1R2-VFT. Functional characterization using intrinsic tryptophan fluorescence revealed that SUMO-hTAS1R2-VFT bound sweet-tasting compounds with affinities consistent with their physiological relevance. Neotame exhibited the highest affinity (Kd ≈ 2 μM), followed by acesulfame-K (Kd ≈ 116 μM) and sucralose (Kd ≈ 282 μM), while sucrose showed weak binding in the millimolar range. These affinities were in agreement with sweetness potency and comparable to those reported for the full-length TAS1R2 subunit. This work provides the first demonstration of soluble expression of functional hTAS1R2-VFT in bacteria, by adding a solubility tag, offering a robust and scalable platform for studying sweetener-receptor interactions and facilitating the rational design of novel sweeteners.
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Valve-in-valve-in-valve (ViViV) implantation will be considered after the second valve deterioration as an increasing number of patients aged < 60 years undergo transcatheter aortic valve replacement (TAVR). We aimed to investigate the hemodynamic outcomes after ViViV procedures. Evolut and Venus A with size of 23 mm and 26 mm were selected for the testing. Cardiovascular hydrodynamic tests were conducted using the in Vitro Pulse Duplicator system. ViViV configuration of 26 mm-in-26 mm-in-26 mm demonstrates a larger effective orifice area (EOA) than the 23 mm-in-26 mm-in-26 mm configuration. The transvalvular mean pressure gradient (MPG) of three 26 mm combination were 8.3 ± 1.9 mmHg for Venus-A and 13.2 ± 1.6 mmHg for Evolut, which were acceptable. The ViViV valve combination employing three 26 mm Venus-A or Evolut self-expanding valves, as opposed to the 23 mm-in-26 mm-in-26 mm configuration, exhibited favorable hemodynamic performance as demonstrated by in the vitro testing.
Synaptosomal-associated protein 47 (SNAP47), a non-canonical SNARE (soluble N-ethylmaleimide-sensitive-factor attachment receptor) protein, is highly expressed in neuronal tissue and exhibits broad cytoplasmic distribution at the cellular level. However, SNAP47 does not directly participate in exocytosis or the recycling of synaptic vesicles (SVs), and its precise physiological function remains elusive. Our previous study revealed that SNAP47 is strongly expressed in GABAergic interneurons (INs) in the hippocampus. Therefore, we created a lentiviral vector carrying a small hairpin RNA (shRNA) to knockdown (KD) SNAP47 and applied this virus to autaptic hippocampal neuronal cultures. To identify GABAergic INs, cultures were prepared using transgenic mice expressing yellow fluorescent protein (YFP)-Venus under the control of the vesicular GABA transporter (VGAT) promoter. SNAP47 KD efficiently reduced the expression of the endogenous SNAP47 in the majority of neurons in autaptic cultures, significantly decreasing the somatic level of the protein. Morphological analysis of INs revealed that SNAP47 KD impacted the morphology with significant reduction in dendrite length. Furthermore, expression of both pre- and postsynaptic markers, was reduced in these neurons. Convergent to these morphological finding, physiological changes were also observed in whole-cell recordings, in particular a decrease in the amplitude and frequency of miniature inhibitory postsynaptic currents (mIPSCs), indicating an alteration in inhibitory synaptic transmission. In contrast, the somato-dendritic morphology and synaptic transmission of YFP-Venus-negative, putative glutamatergic excitatory neurons appeared to remain unaffected. In summary, our results demonstrate that reduced SNAP47 protein expression directly impacts the morphology of GABAergic neurons and their synaptic physiology.
During early development of the placenta, a subset of murine trophectoderm stem cells (TSCs) undergo endoreplication, an unusual form of cell division cycle that decouples DNA synthesis from cytokinesis, resulting in physiological polyploidy. Oscillations in CDK2 activity are essential for the orderly progression of the cell cycle to ensure replicated DNA is accurately partitioned into two daughter cells. However, it remains underexplored how the dynamics of CDK2 activity regulate endoreplication in the context of TSCs differentiation. To address this question, we leveraged the variability in cell fate decisions in an established in vitro system of TSCs differentiation that relies on removal of a growth factor, FGF4, to induce endoreplication. Using quantitative single-cell live confocal microscopy of a precise CDK2 biosensor, DHB-Venus, we identified at least three different outcomes upon FG4 removal: self-renewal, endoreplication, and migration. Our quantitative analyses showed high levels of Cdk2 activity in self-renewing cells whereas intermediate DHB-Venus turnover is linked to increased nuclear and cell size, indicating a shift to endoreplication. Importantly, we also characterize a third class of differentiating TSCs with migratory characteristics that correlate with low levels Cdk2 activity without a change in nuclear size. In sum, our results demonstrated a correlation between different fate outcomes and specific thresholds of CDK2 activity. Our findings show that TSCs can distinguish between different outcomes through modulating the central kinase of the cell cycle, CDK2, positioning it as a key regulator of early trophoblast differentiation.
Non-typeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that causes several respiratory diseases. It employs the Sap (sensitivity to antimicrobial peptide) transporter to achieve resistance against the human antimicrobial peptides (hAMPs). In H. influenzae, the Sap system comprises six subunits, SapABCDFZ, akin to the canonical ATP-binding cassette (ABC) importers. The subunit HiSapA, which plays a role in the substrate binding, has been reported to capture hAMPs such as LL-37 and β-defensins. However, the substrate types and their binding mechanism(s) by HiSapA have not been fully understood. In this study, attempts were made to fill such gaps using in silico approaches. The results of this study suggest that five hAMPs, hBD-2, hBD-3, hNP-1, hNP-4, and hLL-37 can bind to HiSapA with a binding energy ranging from -24.03 to -78.55 kcal mol-1. Further, specific sequence motifs, RRYKQ of hBD-2, PKEEQ of hBD-3, RRYGT of hNP-1, RLVFCR of hNP-4, and LGDFFR of hLL-37, present in the hAMPs, were identified as crucial for HiSapA interaction. In addition, an analysis of the conformational changes and variations in the volumes of the binding-site pocket suggested that there is an increase (from 823 Å3 to 2095 Å3) upon hAMPs binding to HiSapA, indicating its binding mechanism is similar to the previously proposed mechanism, viz. "Venus Flytrap", known for SBPs of ABC importers. In summary, the findings of this study can be utilized for structure-based drug development.
Management of the axilla in early-stage breast cancer has progressively evolved toward less invasive approaches, as advances in tumor biology, imaging, and local and systemic therapies have improved outcomes while highlighting the morbidity associated with axillary surgery. Sentinel lymph node biopsy, once considered essential for staging, is increasingly being questioned in select patients with clinically node-negative disease. This review summarizes current evidence evaluating omission of sentinel lymph node biopsy in early-stage breast cancer, including its impact on oncologic outcomes, quality of life, and implementation in clinical practice. Multiple retrospective studies and randomized controlled trials have demonstrated that omission of axillary surgery does not compromise survival outcomes in carefully selected patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. These findings informed the 2016 Choosing Wisely® recommendation by the Society of Surgical Oncology to avoid routine sentinel lymph node biopsy in women over 70 years of age with clinically node-negative disease. While implementation of this guideline was slower than expected, subsequent studies have explored whether sentinel lymph node biopsy can be safely omitted in a broader group of women with early-stage, HR-positive/HER2-negative invasive breast cancers, who are clinically node-negative on physical exam and preoperative axillary ultrasound. This led to the development of several prospective trials, including SOUND (Sentinel Node vs Observation After Axillary Ultra-Sound), INSEMA (Intergroup Sentinel Mamma), NAUTILUS (No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy), BOOG 2013-08 (Dutch Breast Cancer Research Group 2013-08), OMSLNB (Omission of Sentinel Lymph Node Biopsy), VENUS, and SOAPET (Sentinel node biopsy vs. observation after axillary PET). While many of these trials remain ongoing, results of the SOUND and INSEMA trials demonstrate no difference in survival outcomes following omission of sentinel lymph node biopsy in postmenopausal women with low grade, HR-positive/HER2-negative tumors less than 2 cm in size, and these findings are increasingly being incorporated into clinical practice. Advancements in neoadjuvant therapies have resulted in increasing rates of pathologic complete response in the breast in clinically node-negative women with HER2-positive and triple-negative breast cancers, raising the possibility that sentinel lymph node biopsy may be safely omitted in this population as well. This is being investigated in the EUBREAST-01 (European Breast Cancer Research Association of Surgical Trialists), ASICS (Avoiding Sentinel lymph node biopsy In select Clinical node negative breast cancer patients after neoadjuvant Systemic therapy), ASLAN (Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy), and Neo-NAUTILUS trials. While these trials are ongoing, the results are promising to change the scope of current clinical practice and reduce the morbidity associated with axillary surgery in appropriately selected patients with breast cancer.
Diabetes mellitus requires reliable glycation monitoring, yet tools for monitoring glycation dynamics in real-time within living cells are lacking. Fructosyl valine (FV), a direct indicator of HbA1c glycation, represents a promising target for alternative detection strategies. In this study, a genetically encoded FRET-based biosensor, Fructosyl Valine Sensor (FruValSen), was developed for quantifying FV. The sensor incorporates fructosyl amino acid binding protein SocA between ECFP and Venus, where FV-induced conformational changes modulate the ratiometric fluorescence signal. FruValSen remained stable under alkaline pH conditions in 20 mM MOPS buffer, exhibiting consistent performance across pH variations. The sensor exhibited high specificity for FV, with no significant response to non-glycated sugars, free amino acids, or metal ions. The wild-type sensor achieved a binding affinity (Kd) of 1.6 nM, with a dynamic range of 10 pM to 300 μM, covering physiologically relevant FV concentrations, detecting FV as low as 10 pM and surpassing reported SocA-based sensors. Site-directed mutagenesis of residues I166 and W256 generated affinity variants with altered detection ranges. Confocal microscopy and ratiometric imaging confirmed successful expression in bacterial, yeast, and mammalian cells, with clear cytosolic localization in yeast. Time-dependent FRET analysis in living cells showed a progressive increase in the fluorescence ratio followed by saturation, indicating efficient intracellular FV binding and dynamic response. The sensor was successfully applied for real-time monitoring of FV dynamics at the single-cell level across biological systems. FruValSen provides a sensitive, specific, and real-time platform for non-invasive FV detection in living cells, with relevance for diabetes research.
Carnivorous plants are a paradigm of convergent evolution, yet their genomes reveal even deeper layers of complexity. Recent work has revealed widespread polyploidy in carnivorous plants, including the decaploid East Asian pitcher plant Nepenthes gracilis and hybrid origins for the tetraploid Venus flytrap (Dionaea muscipula), the hexaploid queen sundew (Drosera regia), and the dodecaploid Cape sundew (Drosera capensis). A chromosome-scale genome for the American pitcher plant (Sarracenia purpurea) extends these insights to an independently evolved pitcher lineage. The humped bladderwort (Utricularia gibba) experienced extreme genome compaction while retaining an otherwise typical gene number, challenging assumptions about the evolution of genome size reduction. Molecular convergence is conspicuous among carnivores, from digestive enzyme recruitment to repeated amino acid substitutions under functional constraints. Drosera species further illustrate how centromere type (monocentric vs. holocentric) shapes genome architecture. These discoveries position carnivorous plants as models for studying the plasticity and adaptive landscapes of plant genomes, including tradeoffs between local and global gene duplication and intergenic DNA deletion.
This study aimed to investigate the kokumi-enhancing properties of three N-cinnamoyl-L-aromatic amino acids-N-cinnamoyl-L-phenylalanine (Cin-Phe), N-cinnamoyl-L-tryptophan (Cin-Trp), and N-cinnamoyl-L-tyrosine (Cin-Tyr)-and to elucidate their structure-taste relationships. The compounds were chemically synthesized and structurally confirmed using UPLC-MS/MS and NMR. Dynamic sensory techniques were applied to evaluate their taste-modifying effects in model chicken broth systems. All three compounds significantly enhanced the perception of sweetness, saltiness, and umami at subthreshold concentrations (50-150 μmol/L), with Cin-Trp showing the strongest increase in both intensity and duration. Molecular docking and molecular dynamics simulations indicated that all three compounds stably bound to the Venus-fly-trap (VFT) domain of the calcium-sensing receptor (CaSR). Correlation analysis suggested that the presence of a pyrrole ring and higher hydrophobicity were positively associated with umami enhancement. These findings demonstrate that N-cinnamoyl-L-aromatic amino acids function as promising kokumi enhancers via CaSR activation and provide a structural basis for the rational design of novel taste modulators.