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Electrified synthesis of high-value organonitrogen chemicals from low-cost carbon- and nitrogen-based feedstocks offers an economically and environmentally appealing alternative to traditional thermocatalytic methods. However, the intricate electrochemical reactions at electrode surfaces pose significant challenges in controlling selectivity and activity, especially for producing complex substances such as N,N-dimethylformamide (DMF). Herein, we tackle this challenge by developing relay catalysis for efficient DMF production using a composite WO2-NiOOH/Ni catalyst with two distinctive active sites. Specifically, WO2 selectively promotes dimethylamine (DMA) electrooxidation to produce strongly surface-bound (CH3)2N*, while nearby NiOOH facilitates methanol electrooxidation to yield more weakly bound *CHO. The disparity in binding energetics of the key C- and N-intermediates expedites C-N coupling at the WO2-NiOOH interface. In situ infrared spectroscopy with isotope-labeling experiments, quasi-in situ electron paramagnetic resonance trapping experiments, and electrochemical operating experiments revealed the C-N coupling mechanism and enhanced DMF-synthesis selectivity and activity. In situ X-ray absorption spectroscopy (XAS) and postreaction transmission electron microscopy (TEM) studies verified the stability of WO2-NiOOH/Ni during extended electrochemical operation. A Faradaic efficiency of â¼50% and a production rate of 438 µmol cm-2 h-1 were achieved at an industrially relevant current density of 100 mA cm-2 over an 80 h DMF production period. This study introduces a new paradigm for developing electrothermo relay catalysis for the sustainable and efficient synthesis of valuable organic chemicals with industrial potential.
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Aerobic glycolysis is a metabolic reprogramming of tumor cells that is essential for sustaining their phenotype of fast multiplication by continuously supplying energy and mass. Pyruvate kinase M2 (PKM2) has a vital role in this process, which has given it high interest as a target for anticancer drug development. With potent toxicity to many types of cancer cells, polyphyllin II (PP2), a steroidal saponin isolated from the herbaceous plant Rhizoma paridis, brought to our attention that it might interfere with the PKM2 activity. In this study, we discovered that PP2 was a novel agonist of PKM2. PP2 activated recombinant PKM2 and changed the protein's oligomeric state to activate intracellular PKM2. At the same time, PP2 suppressed its protein kinase function by decreasing the content of nuclear PKM2. The mRNA levels of its downstream genes, such as Glut1, LDHA, and MYC, were inhibited. In addition, PP2 induced oxidative stress by downregulating the expression and activity of antioxidant proteins such as NQO1, TrxR, and Trx in HT-1080 cells, which in turn led to mitochondrial dysfunction and ultimately induced apoptosis. Moreover, PP2 reduced the proliferation and migration of HT-1080 cells. Thus, targeting the glycolysis pathway offers an unprecedented mode of action for comprehending PP2's pharmacological impacts and advances PP2's further development in fibrosarcoma therapy.
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In layered Li-rich materials, over stoichiometric Li forms an ordered occupation of LiTM6 in transition metal (TM) layer, showing a honeycomb superstructure along [001] direction. At the atomic scale, the instability of the superstructure at high voltage is the root cause of problems such as capacity/voltage decay of Li-rich materials. Here a Li-rich material with a high Li/Ni disorder is reported, these interlayer Ni atoms locate above the honeycomb superstructure and share adjacent O coordination with honeycomb TM. These NiâO bonds act as cable-stayed bridge to the honeycomb plane, and improve the high-voltage stability. The cable-stayed honeycomb superstructure is confirmed by in situ X-ray diffraction to have a unique cell evolution mechanism that it can alleviate interlaminar lattice strain by promoting in-plane expansion along a-axis and inhibiting c-axis stretching. Electrochemical tests also demonstrate significantly improved long cycle performance after 500 cycles (86% for Li-rich/Li half cell and 82% for Li-rich/Si-C full cell) and reduced irreversible oxygen release. This work proves the feasibility of achieving outstanding stability of lithium-rich materials through superstructure regulation and provides new insights for the development of the next-generation high-energy-density cathodes.
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Objective: As a traditional Chinese medicine, leech has obvious pharmacological activities in anticoagulantion and antithrombosis. Whitmania pigra Whitman (WP) is the most commonly used leech in the Chinese market. It is often used in clinical applications after high-temperature processing by talcum powder to remove the fishy taste and facilitate crushing. The anticoagulant and thrombolytic active ingredients are protein and polypeptide, which may denaturate and lose activity after high-temperature processing. The rationality of its processing has been questioned in recent years. This study aims to investigate the effect of talcum powder scalding on the antithrombotic activity of WP in vivo and to discuss its pharmacodynamic mechanism in vivo. Methods: Raw and talcum-powdered processed WP were administered intragastrically for 14 days, and carrageenan was injected intraperitoneally to prepare a mouse model of tail vein thrombosis. The incidence rate of tail vein thrombosis and the thrombus area under pathological tissue sections were calculated to evaluate the antithrombotic effect between raw and processed WP. Non-targeted metabolomics was conducted using UPLC-Q-TOF/MS technology to analyze the changes of small molecule metabolites in the body after administration of WP. Results: After intragastric administration, both the raw product and the processed product of WP could inhibit the thrombosis induced by carrageenan, and the processed product had a more apparent antithrombotic effect than the raw product. The administration of WP could regulate the changes of some small molecular metabolites, such as amino acids, lipids, and steroids, in Sphingolipid metabolism and Glycerophospholipid metabolism. Conclusions: Based on the results of pharmacodynamics and metabolomics, processed WP will not reduce the antithrombotic activity of WP. This study provided a scientific basis for the rational use of leeches.
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Acidic CO2 electroreduction (CO2R) using renewable electricity holds promise for high-efficiency generation of storable liquid chemicals with up to 100% CO2 utilization. However, the strong parasitic hydrogen evolution reaction (HER) limits its selectivity and energy efficiency (EE), especially at ampere-level current densities. Here we present that enhancing CO2R intermediate coverage on catalysts promotes CO2R and concurrently suppresses HER. We identified and engineered robust Cu6Sn5 catalysts with strong *OCHO affinity and weak *H binding, achieving 91% Faradaic efficiency (FE) for formic acid (FA) production at 1.2 A cm-2 and pH 1. Notably, the single-pass carbon efficiency reaches a new benchmark of 77.4% at 0.5 A cm-2 over 300 hours. In situ electrochemical Fourier-transform infrared spectroscopy revealed Cu6Sn5 enhances *OCHO coverage ~2.8× compared to Sn at pH 1. Using a cation-free, solid-state-electrolyte-based membrane-electrode-assembly, we produce 0.36 M pure FA at 88% FE over 130 hours with a marked full-cell EE of 37%.
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Polyoxometalate (POM)-pillared Zn-Cr layered double hydroxides (LDHs) exhibited high photocatalytic activities in CO2 reduction and H2O oxidation reactions. For CO2 reduction in pure water, the CO production was 1.17 µmol g-1 after a 24 h reaction. For O2 evolution in NaIO3 solution, the O2 production reached 148.1 µmol g-1 after a 6 hour reaction. A mechanism study indicated that the electron transfer from Zn-Cr LDHs to POMs (SiW12O404-) promoted photocatalytic activities.
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This study shows that exposure to topic-related but irrelevant information enhances both estimates of peer knowledge and our own sense of knowledge. In Experiment 1, participants were more confident in their answers to general knowledge questions and gave higher estimates of peer knowledge when such questions were accompanied by short paragraphs containing topic-related yet nondiagnostic information than when they were not. The inflated peer knowledge estimates were independent of the classic curse of knowledge. Experiments 2, 3, 5, and 6 demonstrated that irrelevant information biases knowledge estimation via its semantic relatedness to the test questions; response latencies were measured in Experiments 5 and 6 to examine the possible role of retrieval fluency in the semantic relatedness effect. Experiment 4 attributed the bias to information content (e.g., "it is generally known that keratin is responsible"), not comments on knowledge popularity (e.g., "what is responsible is generally known"). Importantly, the effect of irrelevant information on estimates of peer knowledge was fully mediated by confidence in own knowledge in Experiments 1, 2, 4, and 5. Experiment 6 manipulated retrieval fluency and failed to find conclusive evidence for its involvement in the semantic relatedness effect. We conclude that irrelevant information boosts peer knowledge estimation through its semantic relatedness to the problem at hand, and the effect is mostly explained by a corresponding increase in the individual's own sense of knowledge. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Rememoração Mental , Semântica , Humanos , Rememoração Mental/fisiologia , Tempo de ReaçãoRESUMO
Mercury is a highly toxic element that is widely present in all types of environmental media and can accumulate in living organisms. Prolonged exposure to high levels of mercury can lead to brain damage and death, so the detection of mercury is of great importance. In this study, a cost-effective and easy-to-operate electrochemical sensing method was successfully developed based on an amino-functionalized titanium-based MXene (NH2-Ti3C2Tx) for the rapid and selective detection of Hg2+ that could have a coordination effect with the -NH2 group of NH2-Ti3C2Tx to promote the efficient accumulation of Hg2+. In this strategy, the NH2-Ti3C2Tx was first modified on glassy carbon electrodes (GCE) to fabricate the electrochemical sensor. Benefiting from the excellent electrical conductivity, abundant active sites, and strong adsorption capacity performance of the NH2-Ti3C2Tx, the NH2-Ti3C2Tx modified GCE (NH2-Ti3C2Tx/GCE) exhibited satisfactory selectivity and enhanced square wave anodic stripping voltammetry (SWASV) measurement for the rapid detection of trace amounts of Hg2+ in aqueous solutions. The electrochemical sensor was found to be capable of detecting Hg2+ with a low detection limit of 8.27 nmol L-1 and a linear range of 0.5 µmol L-1 to 50 µmol L-1. The response time of the electrochemical sensing method was 308 s. In addition, the electrochemical sensing method has good selectivity, repeatability and stability, and multiple heavy metal ions have no effect on its detection, with repeatability and stability RSDs of 1.68% and 1.43%, respectively. Furthermore, the analysis of practical water samples demonstrated that the developed method was highly practical for the actual determination of Hg2+ with recoveries in the range of 99.22-101.90%.
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Mercúrio , Metais Pesados , Mercúrio/análise , Mercúrio/química , Metais Pesados/análise , Água/química , Íons , Carbono/químicaRESUMO
This study aimed to investigate a stratified approach based on hepatitis B virus (HBV) surface antibody (anti-HBs) for managing HBV reactivation (HBVr) in lymphoma patients with serological protection against HBV. A retrospective analysis was conducted on 209 lymphoma patients with a baseline anti-HBs titre of ≥10 iu/L, who were either positive or negative for HBV core antibody (anti-HBc). The results revealed that 15.7% of patients lost serological protection following 6-month anti-lymphoma therapy. With a median follow-up of 28.1 months, the cumulative rates of HBVr at 6 months, 2 years and 4 years were 2.9%, 4.7% and 6.3% respectively. Without intervention, the overall rate of reactivation was 2.0% for patients with isolated anti-HBs and 10.5% for those with positive anti-HBs and anti-HBc. To identify patients at high risk of losing seroprotection and susceptible to HBVr, a predictive model was developed. The high-risk group had significantly higher rates of serological protection loss (27.8% vs. 2.2%) and cumulative incidence of HBVr (22.0% vs. 0%) compared to the low-risk group. Overall, this study highlights the risk of HBVr in lymphoma patients with positive anti-HBs, with or without positive anti-HBc, and recommends periodic monitoring for low-risk patients and early intervention for high-risk patients.
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Hepatite B , Linfoma , Humanos , Vírus da Hepatite B/fisiologia , Rituximab/uso terapêutico , Estudos Retrospectivos , Antígenos de Superfície da Hepatite B , Anticorpos Anti-Hepatite B , Linfoma/tratamento farmacológico , Linfoma/induzido quimicamente , Hepatite B/prevenção & controle , Ativação ViralRESUMO
Carbonic anhydrases (CAs) participate in various physiological and pathological activities by catalyzing the interconversion between carbon dioxide and bicarbonate ions. Under normal circumstances, they guarantee that the relevant biological reactions in our body occur within an appropriate time scale. Abnormal expression or activity alteration of CAs is closely related to the pathogenesis of diverse diseases. This work reports an inhibitor-directed fluorescent probe FMRs-CA for the detection of CAs. Excellent selectivity, favorable biocompatibility, and desirable blood-brain barrier (BBB) penetration endow the probe with the ability to image the fluctuation of CAs in cells and mice. We achieved in situ visualization of the increased CAs in hypoxic cells with this probe. Additionally, probe FMRs-CA was mainly enriched within the liver and gradually metabolized by the liver. With the help of FMRs-CA, the increase of CAs in epileptic mouse brains was revealed first from the perspective of imaging, providing the mechanism connection between abnormal CA expressions and epilepsy.
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Inhibiting thioredoxin reductase (TrxR) to disrupt the redox equilibrium and induce tumor cell apoptosis is a significant tumor therapeutic strategy. Piperine, a natural product from black pepper, has been demonstrated to suppress tumor cell proliferation by enhancing reactive oxygen species (ROS), subsequently leading to cell death. However, the development of Piperine as an active molecule is hampered by its weak cytotoxicity. To develop a compound with higher activity, we synthesized 22 Piperine analogs and evaluated their pharmacological properties. Ultimately, B5 was screened by the results of cytotoxicity and inhibition of TrxR activity. In contrast to Piperine, B5 had significant cytotoxicity with a 4-fold increase. The structure-activity relationship demonstrated that the introduction of an electron-withdrawing group into the benzene ring adjacent to the amino group, particularly in the meta-position, was positive and that shortening the olefin double bond had no appreciable impact on cytotoxicity. Further investigating the physiological activity of B5 in HeLa cells, we found that B5 selectively inhibits the activity of TrxR by binding to Sec residues on TrxR. B5 then induces cellular oxidative stress and finally leads to apoptosis. As a result, the study of B5 paved the way for further investigation into the modification and function of Piperine analogs as TrxR inhibitors.
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Neoplasias , Tiorredoxina Dissulfeto Redutase , Humanos , Células HeLa , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , ApoptoseRESUMO
INTRODUCTION: Previous fMRI studies revealed that the abnormal functional connectivity (FC) was related to cognitive impairment in patients with SLE. However, it remains unclear how the disease severity affects the functional topological organization of the whole-brain network in SLE patients without neuropsychiatric symptoms (non-NPSLE). OBJECTIVE: We aim to examine the impairment of the whole-brain functional network in SLE patients without neuropsychiatric symptoms (non-NPSLE), which may improve the understanding of neural mechanism in SLE. METHODS: We acquired resting-state fMRI data from 32 non-NPSLE patients and 32 healthy controls (HC), constructed their whole-brain functional network, and then estimated the topological properties including global and nodal parameters by using graph theory. Meanwhile, we also investigated the differences in intra- and inter-network FC between the non-NPSLE patients and the HC. RESULTS: The non-NPSLE patients showed significantly lower clustering coefficient, global and local efficiency, but higher characteristic path length than the HC. The non-NPSLE patients had significantly lower nodal strength in two regions, ventromedial prefrontal cortex (vmPFC) and anterior PFC (aPFC) than the HC. We found the non-NPSLE patients had significantly lower intra-network FC within frontal-parietal network (FPN) and within default mode network (DMN), and significantly lower inter-network FC between DMN and FPN than the HC. The intra-network FC within DMN was negatively correlated with systemic lupus erythematosus disease activity index (SLEDAI). CONCLUSION: Abnormal whole-brain functional network properties and abnormal intra- and inter-network FC may be related to cognitive impairment and disease degree in the non-NPSLE patients. Our findings provide a network perspective to understand the neural mechanisms of SLE.
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Disfunção Cognitiva , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Gravidade do PacienteRESUMO
The development of small-molecule probes suitable for live-cell applications remains challenging yet highly desirable. We report the first fluorescent probe, RBH, for imaging the heme oxygenase-1 (HO-1) activity in live cells after discovering hemin as a universal dark quencher. Hemin works via a static quenching mechanism and shows high quenching efficiency (>97 %) with fluorophores across a broad spectrum (λex =400-700â nm). The favorable properties of RBH (e.g. long excitation/emission wavelengths, fast response rate and high magnitude of signal increase) enable its use for determining HO-1 activity in complex biological samples. As HO-1 is involved in regulating antioxidant defence, iron homeostasis and gasotransmitter carbon monoxide production, we expect RBH to be a powerful tool for dissecting its functions. Also, the discovery of hemin as a general static dark quencher provides a straightforward strategy for constructing novel fluorescent probes for diverse biological species.
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Heme Oxigenase-1 , Hemina , Corantes Fluorescentes , Heme Oxigenase (Desciclizante) , AntioxidantesRESUMO
Electrochemical CO2 reduction (CO2R) to ethylene and ethanol enables the long-term storage of renewable electricity in valuable multi-carbon (C2+) chemicals. However, carbon-carbon (C-C) coupling, the rate-determining step in CO2R to C2+ conversion, has low efficiency and poor stability, especially in acid conditions. Here we find that, through alloying strategies, neighbouring binary sites enable asymmetric CO binding energies to promote CO2-to-C2+ electroreduction beyond the scaling-relation-determined activity limits on single-metal surfaces. We fabricate experimentally a series of Zn incorporated Cu catalysts that show increased asymmetric CO* binding and surface CO* coverage for fast C-C coupling and the consequent hydrogenation under electrochemical reduction conditions. Further optimization of the reaction environment at nanointerfaces suppresses hydrogen evolution and improves CO2 utilization under acidic conditions. We achieve, as a result, a high 31 ± 2% single-pass CO2-to-C2+ yield in a mild-acid pH 4 electrolyte with >80% single-pass CO2 utilization efficiency. In a single CO2R flow cell electrolyzer, we realize a combined performance of 91 ± 2% C2+ Faradaic efficiency with notable 73 ± 2% ethylene Faradaic efficiency, 31 ± 2% full-cell C2+ energy efficiency, and 24 ± 1% single-pass CO2 conversion at a commercially relevant current density of 150 mA cm-2 over 150 h.
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Overexpression of the selenoprotein thioredoxin reductase (TrxR) has been documented in malignant tissues and is of pathological significance for many types of tumors. The antibiotic puromycin (Puro) is a protein synthesis inhibitor causing premature polypeptide chain termination during translation. The well-defined action mechanism of Puro makes it a useful tool in biomedical studies. However, the nonselective cytotoxicity of Puro limits its therapeutic applications. We report herein the construction and evaluation of two Puro prodrugs, that is, S1-Puro with a five-membered cyclic disulfide trigger and S2-Puro with a linear disulfide trigger. S1-Puro is selectively activated by TrxR and shows the TrxR-dependent cytotoxicity to cancer cells, while S2-Puro is readily activated by thiols. Furthermore, S1-Puro displays higher stability in plasma than S2-Puro. We expect that this prodrug strategy may promote the further development of Puro as a therapeutic agent.
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Pró-Fármacos , Tiorredoxina Dissulfeto Redutase , Tiorredoxina Dissulfeto Redutase/metabolismo , Pró-Fármacos/farmacologia , Puromicina/farmacologiaRESUMO
Fabrication of high-quality semiconductor thin films has long been a subject of keen interest in the photocatalytic field. Here, we report a facile, solution-based anodic plating and calcination for large-scale synthesis of BiVO4 thin films on indium tin oxide coated glass for use as photoanodes in solar water splitting. Using Na2SO3 as a sacrificial reagent, continuous solar H2 production with 94% Faradaic efficiency was obtained over 6 h of photoelectrochemical water splitting.
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Acidic CO2 reduction (CO2 R) holds promise for the synthesis of low-carbon-footprint chemicals using renewable electricity. However, the corrosion of catalysts in strong acids causes severe hydrogen evolution and rapid deterioration of CO2 R performance. Here, by coating catalysts with an electrically nonconductive nanoporous SiC-NafionTM layer, a near-neutral pH was stabilized on catalyst surfaces, thereby protecting the catalysts against corrosion for durable CO2 R in strong acids. Electrode microstructures played a critical role in regulating ion diffusion and stabilizing electrohydrodynamic flows near catalyst surfaces. This surface-coating strategy was applied to three catalysts, SnBi, Ag, and Cu, and they exhibited high activity over extended CO2 R operation in strong acids. Using a stratified SiC-NafionTM /SnBi/polytetrafluoroethylene (PTFE) electrode, constant production of formic acid was achieved with a single-pass carbon efficiency of >75 % and Faradaic efficiency of >90 % at 100â mA cm-2 over 125â h at pHâ 1.
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The selenoprotein thioredoxin reductase (TrxR) is of paramount importance in maintaining cellular redox homeostasis, and aberrant upregulation of TrxR is frequently observed in various cancers due to their elevated oxidative stress in cells. Thus, it seems promising and feasible to target the ablation of intracellular TrxR for the treatment of cancers. We report herein the design and synthesis of a series of Baylis-Hillman adducts, and identified a typical adduct that possesses the superior cytotoxicity against HepG2 cells over other types of cancer cells. The biological investigation shows the selected typical adduct selectively targets TrxR in HepG2 cells, which thereafter results in the collapse of intracellular redox homeostasis. Further mechanistic studies reveal that the selected typical adduct arrests the cell cycle in G1/G0 phase. Importantly, the malignant metastasis of HepG2 cells is significantly restrained by the selected typical adduct. With well-defined molecular target and mechanism of action, the selected typical adduct, even other Baylis-Hillman skeleton-bearing compounds, merits further development as candidate or ancillary agent for the treatment of various cancers.
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Neoplasias , Tiorredoxina Dissulfeto Redutase , Humanos , Tiorredoxina Dissulfeto Redutase/metabolismo , Estresse Oxidativo , Neoplasias/tratamento farmacológico , OxirreduçãoRESUMO
Photodynamic therapy (PDT) is a non-invasive, light-activated treatment approach that has been broadly employed in cancer. Cyclometallic iridium (Ш) complexes are candidates for ideal photosensitizers due to their unique photophysical and photochemical features, such as high quantum yield, large Stokes shift, strong resistance to photobleaching, and high cellular permeability. We evaluated a panel of iridium complexes and identified PC9 as a powerful photosensitizer to kill cancer cells. PC9 shows an 8-fold increase of cytotoxicity to HeLa cells under light irradiation. Further investigation discloses that PC9 has a strong mitochondrial-targeting ability and can inhibit the antioxidant enzyme thioredoxin reductase, which contributes to improving PDT efficacy. Our data indicate that iridium complexes are efficient photosensitizers with distinct physicochemical properties and cellular actions, and deserve further development as promising agents for PDT.
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Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , Fármacos Fotossensibilizantes/química , Irídio/farmacologia , Irídio/química , Células HeLa , Mitocôndrias , OxirreduçãoRESUMO
BACKGROUND: Previous studies have shown that interpersonal neural synchronization (INS) is a ubiquitous phenomenon between individuals, and recent studies have further demonstrated close associations between INS and shared external sensorimotor input and/or internal mental processes within a dyad. However, most previous studies have employed an observational approach to describe the behavior-INS correlation, leading to difficulties in causally disentangling the relationship among INS, external sensorimotor input and the internal mental process. OBJECTIVE/HYPOTHESIS: The present study aimed to directly change the level of INS through anodal transcranial direct current stimulation (tDCS) to test whether the change in INS would directly impact the internal mental process (Hypothesis 1) or indirectly through external sensorimotor input; the interaction behaviors were also changed (Hypothesis 2) or not (Hypothesis 3). METHODS: Thirty pairs of romantically involved heterosexual couples were recruited for a within-subjects design. Three conditions were assessed: a true stimulation condition with 20-min anodal high-definition tDCS to the right anterior temporal lobe (rATL) of women before they communicated with their partners, a sham stimulation condition and a control brain region stimulation condition. The comparison between the true and sham or control brain region conditions allows us to detect the true effect of brain stimulation on INS. Functional near-infrared spectroscopy (fNIRS) hyperscanning was used to simultaneously collect dyadic participants' hemodynamic signals during communication. INS, empathy, and interaction behaviors were examined and compared among different stimulation conditions. RESULTS: True brain stimulation significantly decreased INS between the rATL of the women and sensorimotor cortex (SMC) of the men compared to the sham stimulation condition (t(27.8) = -2.821, P = 0.009, d = 0.714) and control brain region stimulation condition (t(27.2) = -2.606, P = 0.015, d = 0.664) during communication. It also significantly decreased the level of emotional empathy (F(2,145) = 6.893, P = 0.001) but did not change sensorimotor processes, such as verbal or nonverbal interaction behaviors. However, nonverbal behaviors mediated the relationship between the changes in INS and emotional empathy (lower limit confidence interval = 0.01, upper limit confidence interval = 2.66). CONCLUSION(S): These findings support the third hypothesis, suggesting that INS is associated with the shared internal mental process indirectly via the sensorimotor process, but the sensorimotor process itself does not covary with the INS and the associated internal mental process. These results provide new insight into the hierarchical architecture of dual-brain function from a bottom-up perspective.