Identification of patients with locally advanced rectal cancer eligible for neoadjuvant chemotherapy alone: Results of a retrospective study.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (nCT) appears in a few clinical studies as an alternative to neoadjuvant chemoradiation (nCRT) in selected patients with locally advanced rectal cancer (LARC). We aimed to compare the clinical outcomes of nCT with or without nCRT in patients with LARC and to identify patients who may be suitable for nCT alone. MATERIALS AND METHODS: A total of 155 patients with LARC who received neoadjuvant treatment (NT) were retrospectively analysed from January 2016 to June 2021. The patients were divided into two groups: nCRT (n = 101) and nCT (n = 54). More patients with locally advanced disease (cT4, cN+ and magnetic resonance imaging-detected mesorectal fascia [mrMRF] positive [+]) were found in the nCRT group. Patients in the nCRT group received a dose of 50 Gy/25 Fx irradiation with concurrent capecitabine, and the median number of nCT cycles was two. In the nCT group, the median number of cycles was four. RESULTS: The median follow-up duration was 30 months. The pathologic complete response (pCR) rate in the nCRT group was significantly higher than that in the nCT group (17.5% vs. 5.6%, p = 0.047). A significant difference was observed in the locoregional recurrence rate (LRR); 6.9% in the nCRT group and 16.7% in the nCT group (p = 0.011). Among patients with initial mrMRF (+) status, the LRR in the nCRT group was significantly lower than that in the nCT group (6.1% vs. 20%, p = 0.007), but not in patients with initial mrMRF negative (-) (10.5% in each group, p = 0.647). Compared with the nCT group, a lower LRR was observed in patients in the nCRT group with initial mrMRF (+) converted to mrMRF (-) after NT (5.3% vs. 23%, p = 0.009). No significant difference was observed between the two groups regarding acute toxicity and overall and progression-free survivals. Multivariate analysis showed that nCRT and ypN stage were independent prognostic factors for the development of LRR. CONCLUSION: Patients with initial mrMRF (-) may be suitable for nCT alone. However, patients with initial mrMRF (+) converted to mrMRF (-) after nCT are still at high risk of LRR, and radiotherapy is recommended. Prospective studies are required to confirm these findings.

Consequences of depleting TNRC6, AGO, and DROSHA proteins on expression of microRNAs.

The potential for microRNAs (miRNAs) to regulate gene expression remains incompletely understood. DROSHA initiates the biogenesis of miRNAs while variants of Argonaute (AGO) and Trinucleotide Repeat Containing Six (TNRC6) family proteins form complexes with miRNAs to facilitate RNA recognition and gene regulation. Here we investigate the fate of miRNAs in the absence of these critical RNAi protein factors. Knockout of DROSHA expression reduces levels of some miRNAs annotated in miRbase but not others. The identity of miRNAs with reduced expression matches the identity of miRNAs previously identified by experimental approaches. The miRgeneDB resource offers closest alignment with experimental results. By contrast, the loss of TNRC6 proteins had much smaller effects on miRNA levels. Knocking out AGO proteins, which directly contact the mature miRNA, decreased expression of the miRNAs most strongly associated with AGO2 as determined from enhanced crosslinking immunoprecipitation (AGO2-eCLIP). Evaluation of miRNA binding to endogenously-expressed AGO proteins revealed that miRNA:AGO association was similar for AGO1, AGO2, AGO3, and AGO4. Our data emphasize the need to evaluate annotated miRNAs based on approximate cellular abundance, DROSHA dependence, and physical association with AGO when forming hypotheses related to their function.

Activity-Stability Balance: The Role of Electron Supply Effect of Support in Acidic Oxygen Evolution.

Developing efficient and durable electrocatalysts for the oxygen evolution reaction (OER) in proton exchange membrane (PEM) electrolyzers represents a significant challenge. Herein, the cobalt-ruthenium oxide nano-heterostructures are successfully synthesized on carbon cloth (CoOx /RuOx -CC) for acidic OER through a simple and fast solution combustion strategy. The rapid oxidation process endows CoOx /RuOx -CC with abundant interfacial sites and defect structures, which enhances the number of active sites and the charge transfer at the electrolyte-catalyst interface, promoting the OER kinetics. Moreover, the electron supply effect of the CoOx support allows electrons to transfer from Co to Ru sites during the OER process, which is beneficial to alleviate the ion leaching and over-oxidation of Ru sites, improving the catalyst activity and stability. As a self-supported electrocatalyst, CoOx /RuOx -CC displays an ultralow overpotential of 180 mV at 10 mA cm-2 for OER. Notably, the PEM electrolyzer using CoOx /RuOx -CC as the anode can be operated at 100 mA cm-2 stably for 100 h. Mechanistic analysis shows that the strong catalyst-support interaction is beneficial to redistribute the electronic structure of RuO bond to weaken its covalency, thereby optimizing the binding energy of OER intermediates and lowering the reaction energy barrier.

The Physiological Functions and Polymorphisms of Type II Deiodinase.

Type II deiodinase (DIO2) is thought to provide triiodothyronine (T3) to the nucleus to meet intracellular needs by deiodinating the prohormone thyroxine. DIO2 is expressed widely in many tissues and plays an important role in a variety of physiological processes, such as controlling T3 content in developing tissues (e.g., bone, muscles, and skin) and the adult brain, and regulating adaptive thermogenesis in brown adipose tissue (BAT). However, the identification and cloning of DIO2 have been challenging. In recent years, several clinical investigations have focused on the Thr92Ala polymorphism, which is closely correlated with clinical syndromes such as type 2 diabetes, obesity, hypertension, and osteoarthritis. Thr92Ala-DIO2 was also found to be related to bone and neurodegenerative diseases and tumors. However, relatively few reviews have synthesized research on individual deiodinases, especially DIO2, in the past 5 years. This review summarizes current knowledge regarding the physiological functions of DIO2 in thyroid hormone signaling and adaptive thermogenesis in BAT and the brain, as well as the associations between Thr92Ala-DIO2 and bone and neurodegenerative diseases and tumors. This discussion is expected to provide insights into the physiological functions of DIO2 and the clinical syndromes associated with Thr92Ala-DIO2.

Bisazapentalene Dication: Global Aromaticity and Open-Shell Singlet Ground State.

Antiaromatic moieties fused in polycyclic π-conjugated molecules usually exhibit strong localized antiaromaticiy. Herein, we reported the synthesis and properties of a bisazapentalene dication (BAP2+) obtained from in situ two-electron oxidation of neutral species 8. Noteworthily, it possesses global aromaticity and an open-shell singlet ground state. This study underlines the importance of heteroatoms in determining the delocalization of π-electrons and the aromaticity of molecules in their oxidized states.

Aromaticity in Fully π-Conjugated Multicyclic Macrocycles.

The research on aromaticity has mainly focused on monocyclic [n]annulene-like systems or polycyclic aromatic hydrocarbons. For fully π-conjugated multicyclic macrocycles (MMCs), the electronic coupling between the individual constitutional macrocycles would lead to unique electronic structures and aromaticity. The studies on MMCs, however, are quite limited, presumably due to the great challenges to design and synthesize a fully π-conjugated MMC molecule. Herein, we report the facile synthesis of two MMCs (2TMC and 3TMC) in which two and three thiophene-based macrocycles are fused together by employing both intramolecular and intermolecular Yamamoto coupling reactions of a properly designed precursor (7). The monocyclic macrocycle (1TMC) was also synthesized as a model compound. The geometry, aromaticity, and electronic properties of these macrocycles at different oxidation states were investigated by X-ray crystallographic analysis, NMR, and theoretical calculations, which disclosed how the constitutional macrocycles interplay with each other and lead to unique aromatic/antiaromatic character. This study provides new insights into the complex aromaticity in MMC systems.

Integrated assessment and critical obstacle diagnosis of rural resource and environmental carrying capacity with a social-ecological framework: a case study of Liyang county, Jiangsu Province.

The contradiction among human being, resources, and environment has become a significant obstacle to achieving sustainable development, especially in rural areas subject to the spillover of urban development elements. With the immense strain of resources and environment, it is critical to assess whether human activities fall within the carrying capacity range of a natural ecosystem in a rural system. Taking the rural areas of Liyang county as an example, this study aims to assess the rural resource and environmental carrying capacity (RRECC) and diagnose its critical obstacles. Firstly, a social-ecological framework focusing on human-environment interaction was employed to construct the RRECC indicator system. Subsequently, the entropy-TOPSIS method was introduced to assess the performance of the RRECC. Finally, the obstacle diagnosis method was applied to identify the critical obstacles of RRECC. Our results show that the distribution of RRECC presents a spatial heterogeneity, with high- and medium-high-level villages primarily concentrated in the south of the study area, where there are abundant hills and ecological lakes. Medium-level villages are scattered throughout each town, and low and medium-low level villages are concentrated across all the towns. Moreover, the resource subsystem of RRECC (RRECC_RS) exhibits a similar spatial distribution to RRECC, while the outcome subsystem of RRECC (RRECC_OS) has a comparable quantity proportion of different levels to RRECC. Furthermore, the diagnosis results of critical obstacle vary between the town scale divided by administrative units and the regional scale divided by RRECC values. In detail, arable land occupied by construction is the main critical obstacle at the town scale, while the poor people in villages, people left-behind, and arable land occupied by construction are the main critical obstacles at the regional scale. Targeted differentiated improvement strategies for RRECC at regional scale from various perspectives of global, local, and single are proposed. This research can serve as a theoretical foundation for assessing RRECC and developing differentiated sustainable development strategies for the path forward to rural revitalization.

IL-1ß-associated NNT acetylation orchestrates iron-sulfur cluster maintenance and cancer immunotherapy resistance.

Interleukin-1ß (IL-1ß) is a key protein in inflammation and contributes to tumor progression. However, the role of IL-1ß in cancer is ambiguous or even contradictory. Here, we found that upon IL-1ß stimulation, nicotinamide nucleotide transhydrogenase (NNT) in cancer cells is acetylated at lysine (K) 1042 (NNT K1042ac) and thereby induces the mitochondrial translocation of p300/CBP-associated factor (PCAF). This acetylation enhances NNT activity by increasing the binding affinity of NNT for NADP+ and therefore boosts NADPH production, which subsequently sustains sufficient iron-sulfur cluster maintenance and protects tumor cells from ferroptosis. Abrogating NNT K1042ac dramatically attenuates IL-1ß-promoted tumor immune evasion and synergizes with PD-1 blockade. In addition, NNT K1042ac is associated with IL-1ß expression and the prognosis of human gastric cancer. Our findings demonstrate a mechanism of IL-1ß-promoted tumor immune evasion, implicating the therapeutic potential of disrupting the link between IL-1ß and tumor cells by inhibiting NNT acetylation.

Cathepsin B S-nitrosylation promotes ADAR1-mediated editing of its own mRNA transcript via an ADD1/MATR3 regulatory axis.

Genetic information is generally transferred from RNA to protein according to the classic "Central Dogma". Here, we made a striking discovery that post-translational modification of a protein specifically regulates the editing of its own mRNA. We show that S-nitrosylation of cathepsin B (CTSB) exclusively alters the adenosine-to-inosine (A-to-I) editing of its own mRNA. Mechanistically, CTSB S-nitrosylation promotes the dephosphorylation and nuclear translocation of ADD1, leading to the recruitment of MATR3 and ADAR1 to CTSB mRNA. ADAR1-mediated A-to-I RNA editing enables the binding of HuR to CTSB mRNA, resulting in increased CTSB mRNA stability and subsequently higher steady-state levels of CTSB protein. Together, we uncovered a unique feedforward mechanism of protein expression regulation mediated by the ADD1/MATR3/ADAR1 regulatory axis. Our study demonstrates a novel reverse flow of information from the post-translational modification of a protein back to the post-transcriptional regulation of its own mRNA precursor. We coined this process as "Protein-directed EDiting of its Own mRNA by ADAR1 (PEDORA)" and suggest that this constitutes an additional layer of protein expression control. "PEDORA" could represent a currently hidden mechanism in eukaryotic gene expression regulation.

The Effect of Oyster Shell Powder on the High-Temperature-Properties of Slag-Ceramic Powder-Based Geopolymer.

There is a lack of scientific understanding of adding an oyster shell powder (OSP) to geopolymer concrete. The purpose of this study is: (1) to evaluate the high-temperature resistance of the alkali-activated slag ceramic powder (CP) mixture added with OSP at different temperatures, (2) to address the lack of application of environmentally friendly building materials, and (3) to reduce solid waste of OSP pollution and protect the environment. OSP replaces granulated blast furnace slag (GBFS) and CP at 10% and 20% (based on binder), respectively. The mixture was heated to 400.0, 600.0, and 800.0 °C after curing for 180 days. The results of the experiment are summarized as follows: (1) The thermogravimetric (TG) results indicated that the OSP20 samples produced more CASH gels than the control OSP0. (2) As the temperature increased, the compressive strength and ultrasonic pulse velocity (UPV) both decreased. (3) Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) results reveal that the mixture undergoes a phase transition at 800.0 °C, and compared with the control OSP0, OSP20 undergoes a different phase transition. (4) The size change and appearance image results indicate that the mixture with added OSP inhibits shrinkage, and calcium carbonate decomposes to produce off-white CaO. To sum up, adding OSP can effectively reduce the damage of high temperatures (800.0 °C) on the properties of alkali-activated binders.

Neuroprotective effect of engineered Clostridiumbutyricum-pMTL007-GLP-1 on Parkinson's disease mice models via promoting mitophagy.

Parkinson's disease (PD) is a common neurodegenerative disease with limited treatment and no cure, hence, broadening PD drug spectrum is of great significance. At present, engineered microorganisms are attracting increasing attention. In this study, we constructed an engineered strain of Clostridium butyricum-GLP-1, a C. butyricum (a probiotic) that consistently expresses glucagon-like peptide-1 (GLP-1, a peptide-based hormone with neurological advantage) in anticipation of its use in PD treatment. We further investigated the neuroprotective mechanism of C. butyricum-GLP-1 on PD mice models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The results indicated that C. butyricum-GLP-1 could improve motor dysfunction and ameliorate neuropathological changes by increasing TH expression and reducing the expression of α-syn. Moreover, we confirmed that C. butyricum-GLP-1 improved microbiome imbalance of PD mice by decreasing the relative abundance of Bifidobacterium at the genus level, improved gut integrity, and upregulated the levels of GPR41/43. Surprisingly, we found it could exert its neuroprotective effects via promoting PINK1/Parkin mediated mitophagy and attenuating oxidative stress. Together, our work showed that C. butyricum-GLP-1 improves PD by promoting mitophagy, which provides an alternative therapeutic modality for PD.

Microcrystalline cellulose grafted hyperbranched polyester with roll comb structure for synergistic toughening and strengthening of microbial PHBV/bio-based polyester elastomer composites.

The brittle feature of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is the major challenge that strongly restricts its application at present. Successfully synthesized bio-based engineering polyester elastomers (BEPE) were combined with PHBV to create entirely bio-composites with the intention of toughening PHBV. Herein, the 2,2-Bis(hydroxymethyl)-propionic acid (DMPA) was grafted onto microcrystalline cellulose (MCC) and then further transformed into hyperbranched polyester structure via polycondensation. The modified MCC, named MCHBP, had plenty of terminal hydroxyl groups, which get dispersed between PHBV and BEPE. Besides, a large number of terminal hydroxyl groups of MCHBP can interact with the carbonyl groups of PHBV or BEPE in a wide range of hydrogen bonds, and subsequently increase the adhesion and stress transfer between the PHBV and BEPE. The tensile toughness and the elongation at break of the PHBV/BEPE composites with 0.5phr MCHBP were improved by 559.7 % and 221.8 % in comparison to those of PHBV/BEPE composites. Results also showed that MCHBP can play a heterogeneous nucleation effect on the crystallization of PHBV. Therefore, this research can address the current issue of biopolymers' weak mechanical qualities and may have uses in food packaging.

Endoscopic retrograde stent drainage therapies for malignant biliary obstruction: the distal opening of stent location above or across the duodenal papilla? A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the efficacy and safety of the method of placing the distal stent opening above the duodenal papilla (hereinafter referred to Above method) for endoscopic retrograde stent internal drainage in MBO patients. METHODS: PubMed, Embase, Web of science and Cochrane databases were searched to identify clinical studies comparing the stent distal opening mounted above the papilla and across the papilla (hereinafter referred to Across method), Comparison indicators included stent patency, stent occlusion rate, clinical success rate, overall complication rate, postoperative cholangitis rate, and overall survival. Revman5.4 software was used for meta-analysis, funnel plot and publication bias and Egger's test were completed by Stata14.0 software. RESULTS: A total of 11 clinical studies (8 case-control studies, 3 RCT studies) were included, with a total of 751 patients (318 cases in the Above group and 433 cases Across group). The overall patency of Above method was longer than that of Across method (HR = 0.60, 95%CI [0.46-0.78], p < 0.001). Subgroup analysis showed statistical difference using plastic stent (HR = 0.49, 95%CI [0.33,0.73], p < 0.001). Inversely, there didn't exist significant difference in which metal stent were adopted (HR= 0.74, 95%CI [0.46,1.18], p = 0.21). Similarly, there also without statistical difference between patients with plastic stent placed above the papilla and metal stent mounted Across the papilla (HR = 0.73, 95%CI [0.15,3.65], p = 0.70). Moreover, the overall complication rate of the Above method was lower than that of the Across method (OR = 0.48,95%CI [0.30,0.75], p = 0.002). On the contrary, the differences of stent occlusion rate (OR = 0.86,95%CI [0.51,1.44], p = 0.56), overall survival (HR = 0.90, 95%CI [0.71,1.13]), p = 0.36), the clinical success rate (OR = 1.30, 95%CI [0.52,3.24], p = 0.57) and postoperative cholangitis rats (OR = 0.73, 95%CI [0.34,1.56], p = 0.41) were not statistically significant. CONCLUSIONS: The distal opening of the stent can be placed above the duodenal main papilla for eligible MBO patients who receiving endoscopic retrograde stent drainage treatment, which can effectively prolong the patency duration when plastic stent is used, and reduce the overall risk of complications.

The Arabidopsis pre-mRNA 3' end processing related protein FIP1 promotes seed dormancy via the DOG1 and ABA pathways.

Seed dormancy is an important adaptive trait to prevent germination occurring at an inappropriate time. The mechanisms governing seed dormancy and germination are complex. Here, we report that FACTOR INTERACTING WITH POLY(A) POLYMERASE 1 (FIP1), a component of the pre-mRNA 3' end processing machinery, is involved in seed dormancy and germination processes in Arabidopsis thaliana. FIP1 is mainly expressed in seeds and the knockout of FIP1 causes reduced seed dormancy, indicating that FIP1 positively influences seed dormancy. Meanwhile, fip1 mutants are insensitive to exogenous ABA during seed germination and early seedling establishment. The terms 'seed maturation' and 'response to ABA stimulus' are significantly enriched in a gene ontology analysis based on genes differentially expressed between fip1-1 and the wild type. Several of these genes, including ABI5, DOG1 and PYL12, show significantly decreased transcript levels in fip1. Genetic analysis showed that either cyp707a2 or dog1-5 partially, but in combination completely, represses the reduced seed dormancy of fip1, indicating that the double mutant cyp707a2 dog1-5 is epistatic to fip1. Moreover, FIP1 is required for CFIM59, another component of pre-mRNA 3' end processing machinery, to govern seed dormancy and germination. Overall, we identified FIP1 as a regulator of seed dormancy and germination that plays a crucial role in governing these processes through the DOG1 and ABA pathways.

Convergent Synthesis of the Precursors to Thiophene-Based Quinoids.

A convergent (outside-to-center) route was adopted to synthesize the precursors of quinoidal compounds in high yields of 85-93%. With subsequent rearrangement/dehydroxylation and oxidation, a series of thiophene-based quinoids with indandione or oxindole terminal groups were successfully synthesized. This strategy shows good compatibility with versatile central and terminal units, leading to quinoidal compounds with tunable properties.

Source apportionment of heavy metals and their effects on the species diversity of plant communities in the Caizi Lake wetland, China.

This study investigated the effects of heavy metals on the species diversity of the Xinjian Dyke Wetland, an ecosystem where reclaimed farmlands are being transformed back into wetlands through the introduction of indigenous plants. The sources of soil heavy metals were analyzed, and correlation analyses were conducted to assess the relationships between heavy metal content and biodiversity indices. The results indicated that (1) the mean contents of Hg, Cd, Cu, Zn, As, Cr, and Pb were higher than the control values, with the content of Hg, Cd, Cu, and Zn exceeding the national standard; (2) the soil heavy metals mainly came from pesticides, chemical fertilizer, transportation, sewage irrigation, and the soil matrix; and (3) Hg and As were not significantly correlated with the diversity indices, but there was a highly positive correlation for Cu, Cr, and Pb, and a significant negative correlation for Zn and Cd. Collectively, our findings indicated that heavy metals have different effects on the plant species diversity inXinjian Dyke reconstruction area. The ecological restoration of wetlands from reclaimed farmlands should reasonably increase tolerant species and maximize the ecological niche differentiation of the species. Moreover, functionally redundant species should not be planted.

Proteomics identifies differentially expressed proteins in glioblastoma U87 cells treated with hederagenin.

OBJECTIVE: We investigated differentially expressed proteins (DEPs) in human glioblastoma U87 cells after treatment with hederagenin as a therapeutic screening mechanism and provided a theoretical basis for hederagenin in treating glioblastoma. METHODS: The Cell Counting Kit 8 assay was used to analyze the inhibitory effect of hederagenin on the proliferation of U87 cells. Protein was identified by tandem mass tags and LC-MS/MS analysis techniques. Annotation of DEPs, Gene Ontology enrichment and function, and Kyoto Encyclopedia of Genes and Genomes pathways and domains were all examined by bioinformatics. According to the TMT results, hub protein was selected from DEPs for WB verification. RESULTS: Protein quantitative analysis found 6522 proteins in total. Compared with the control group, 43 DEPs (P < 0.05) were involved in the highly enriched signaling pathway in the hederagenin group, among which 20 proteins were upregulated, and 23 proteins were downregulated. These different proteins are mainly involved in the longness regulating pathway-WORM, the hedgehog signaling pathway, Staphylococcus aureus infection, complement, coagulation cascades, and mineral absorption. KIF7 and ATAD2B expression were significantly down-regulated and PHEX and TIMM9 expression were significantly upregulated, according to WB analysis, supporting the TMT findings. CONCLUSION: Hederagenin inhibition of GBM U87 cells may be related to KIF7, which is mainly involved in the hedgehog signaling pathway. Our findings lay a foundation for additional study of the therapeutic mechanism of hederagenin.

A Rational Design of Metal-Organic Framework Nanozyme with High-Performance Copper Active Centers for Alleviating Chemical Corneal Burns.

Metal-organic frameworks (MOFs) have attracted significant research interest in biomimetic catalysis. However, the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a significant challenge. Inspired by metalloenzymes with well-defined coordination structures, a series of MOFs containing halogen-coordinated copper nodes (Cu-X MOFs, X = Cl, Br, I) are employed to elucidate their structure-activity relationship. Intriguingly, experimental and theoretical results strongly support that precisely tuning the coordination of halogen atoms directly regulates the enzyme-like activities of Cu-X MOFs by influencing the spatial configuration and electronic structure of the Cu active center. The optimal Cu-Cl MOF exhibits excellent superoxide dismutase-like activity with a specific activity one order of magnitude higher than the reported Cu-based nanozymes. More importantly, by performing enzyme-mimicking catalysis, the Cu-Cl MOF nanozyme can significantly scavenge reactive oxygen species and alleviate oxidative stress, thus effectively relieving ocular chemical burns. Mechanistically, the antioxidant and antiapoptotic properties of Cu-Cl MOF are achieved by regulating the NRF2 and JNK or P38 MAPK pathways. Our work provides a novel way to refine MOF nanozymes by directly engineering the coordination microenvironment and, more significantly, demonstrating their potential therapeutic effect in ophthalmic disease.

Enhanced external counterpulsation modulates the heartbeat evoked potential.

Introduction: Accumulating evidence suggests that enhanced external counterpulsation (EECP) influences cardiac functions, hemodynamic characteristics and cerebral blood flow. However, little is known about whether or how the EECP affects the brain-heart coupling to produce these physiological and functional changes. We aimed to determine if the brain-heart coupling is altered during or after EECP intervention by assessing the heartbeat evoked potential (HEP) in healthy adults. Methods: Based on a random sham-controlled design, simultaneous electroencephalography and electrocardiography signals as well as blood pressure and flow status data were recorded before, during and after two consecutive 30-min EECP in 40 healthy adults (female/male: 17/23; age: 23.1 ± 2.3 years). HEP amplitude, frequency domain heart rate variability, electroencephalographic power and hemodynamic measurements of 21 subjects (female/male: 10/11; age: 22.7 ± 2.1 years) receiving active EECP were calculated and compared with those of 19 sham control subjects (female/male: 7/12; age: 23.6 ± 2.5 years). Results: EECP intervention caused immediate obvious fluctuations of HEP from 100 to 400 ms after T-peak and increased HEP amplitudes in the (155-169) ms, (354-389) ms and (367-387) ms time windows after T-peak in the region of the frontal pole lobe. The modifications in HEP amplitude were not associated with changes in the analyzed significant physiological measurements and hemodynamic variables. Discussion: Our study provides evidence that the HEP is modulated by immediate EECP stimuli. We speculate that the increased HEP induced by EECP may be a marker of enhanced brain-heart coupling. HEP may serve as a candidate biomarker for the effects and responsiveness to EECP.