Study on adsorption of kaolinite and gold thiosulfate.

The adsorption behavior of gold thiosulfate ions on the surface of kaolinite was studied using a combination of experimental research and quantum chemical calculations. Under the condition of a stirring time of 30 min, a stirring speed of 500 r·min-1, and a mass ratio of 30% kaolinite in the slurry, when the initial gold concentration of 56.50 mg·L-1,the adsorption rate of gold-thiosulfate ions from a kaolinite-containing solution was 7.44%. The results of Fourier transform infrared spectroscopy (FTIR) and energy dispersive spectroscopy (EDS) showed that the physical and chemical adsorption of kaolinite and gold thiosulfate occurred in solution. Quantum chemical calculations were performed using the CASTEP module in Materials Studio. The adsorption energy of gold thiosulfate on the surface of kaolinite (001) was calculated as - 438.01 kJ·mol-1.The calculated H76-O289 distance was 1.615 Å. Mulliken Charge population analysis and bond population analysis showed that gold thiosulfate ions form relatively stable bonds on the kaolinite surface (001). In the process of thiosulfate immersion, part of gold is adsorbed by kaolinite, which affects the extraction of gold. These results indicate that during the leaching process of gold thiosulfate, kaolinite has the ability to "catch" gold, which affects the leaching efficiency.

Gastric Cancer Assembloids Derived from Patient-Derived Xenografts: A Preclinical Model for Therapeutic Drug Screening.

The construction of reliable preclinical models is crucial for understanding the molecular mechanisms involved in gastric cancer and for advancing precision medicine. Currently, existing in vitro tumor models often do not accurately replicate the human gastric cancer environment and are unsuitable for high-throughput therapeutic drug screening. In this study, droplet microfluidic technology is employed to create novel gastric cancer assembloids by encapsulating patient-derived xenograft gastric cancer cells and patient stromal cells in Gelatin methacryloyl (GelMA)-Gelatin-Matrigel microgels. The usage of GelMA-Gelatin-Matrigel composite hydrogel effectively alleviated cell aggregation and sedimentation during the assembly process, allowing for the handling of large volumes of cell-laden hydrogel and the uniform generation of assembloids in a high-throughput manner. Notably, the patient-derived xenograft assembloids exhibited high consistency with primary tumors at both transcriptomic and histological levels, and can be efficiently scaled up for preclinical drug screening efforts. Furthermore, the drug screening results clearly demonstrated that the in vitro assembloid model closely mirrored in vivo drug responses. Thus, these findings suggest that gastric cancer assembloids, which effectively replicate the in vivo tumor microenvironment, show promise for enabling more precise high-throughput drug screening and predicting the clinical outcomes of various drugs.

Graph Convolutional Network with Self-supervised Learning for Brain Disease Classification.

Brain functional network (BFN) analysis has become a popular method for identifying neurological diseases at their early stages and revealing sensitive biomarkers related to these diseases. Due to the fact that BFN is a graph with complex structure, graph convolutional networks (GCNs) can be naturally used in the identification of BFN, and can generally achieve an encouraging performance if given large amounts of training data. In practice, however, it is very difficult to obtain sufficient brain functional data, especially from subjects with brain disorders. As a result, GCNs usually fail to learn a reliable feature representation from limited BFNs, leading to overfitting issues. In this paper, we propose an improved GCN method to classify brain diseases by introducing a self-supervised learning (SSL) module for assisting the graph feature representation. We conduct experiments to classify subjects with mild cognitive impairment (MCI) and autism spectrum disorder (ASD) respectively from normal controls (NCs). Experimental results on two benchmark databases demonstrate that our proposed scheme tends to obtain higher classification accuracy than the baseline methods.

Discovery of a Series of 4-Amide-thiophene-2-carboxyl Derivatives as Highly Potent P2Y14 Receptor Antagonists for Inflammatory Bowel Disease Treatment.

The P2Y14 receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y14 receptor antagonists based on the scaffold hopping strategy. The optimized compound 39 (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC50: 0.40 nM). Moreover, compound 39 demonstrated notably improved solubility, liver microsomal stability, and oral bioavailability. Fluorescent ligand binding assay confirmed that 39 has the binding ability to the P2Y14 receptor, and molecular dynamics (MD) simulations revealed the formation of a unique intramolecular hydrogen bond (IMHB) in the binding conformation. In the experimental colitis mouse model, compound 39 showed a remarkable anti-IBD effect even at low doses. Compound 39, with a potent anti-IBD effect and favorable druggability, can be a promising candidate for further research. In addition, this work lays a strong foundation for the development of P2Y14 receptor antagonists and the therapeutic strategy for IBD.

Flexible Multimodal Sensors Enhanced by Electrospun Lead-Free Perovskite and PVDF-HFP Composite Form-Stable Mesh Membranes for In Situ Plant Monitoring.

The pH and humidity of the crop environment are essential indicators for monitoring crop growth status. This study reports a lead-free perovskite/polyvinylidene fluoride-hexafluoropropylene composite (LPPC) to enhance the stability and reliability of in situ plant pH and humidity monitoring. The mesh composite membrane of LPPC illustrates a hydrophobic contact angle of 101.982°, a tensile strain of 800%, and an opposing surface potential of less than -184.9 mV, which ensures fast response, high sensitivity, and stability of the sensor during long-term plant monitoring. The LPPC-coated pH electrode possesses a sensitivity of -63.90 mV/pH, which provides a fast response within 5 s and is inert to environmental temperature interference. The LPPC-coated humidity sensor obtains a sensitivity of -145.7 Ω/% RH, responds in 28 s, and works well under varying light conditions. The flexible multimodal sensor coated with an LPPC membrane completed real-time in situ monitoring of soilless strawberries for 17 consecutive days. Satisfactory consistency and accuracy performance are observed. The study provides a simple solution for developing reliable, flexible wearable multiparameter sensors for in situ monitoring of multiple parameters of crop environments.

SWI/SNF chromatin remodeling factor BAF60b restrains inflammatory diseases by affecting regulatory T cell migration.

Regulatory T (Treg) cells play a critical regulatory role in the immune system by suppressing excessive immune responses and maintaining immune balance. The effective migration of Treg cells is crucial for controlling the development and progression of inflammatory diseases. However, the mechanisms responsible for directing Treg cells into the inflammatory tissue remain incompletely elucidated. In this study, we identified BAF60b, a subunit of switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complexes, as a positive regulator of Treg cell migration that inhibits the progression of inflammation in experimental autoimmune encephalomyelitis (EAE) and colitis animal models. Mechanistically, transcriptome and genome-wide chromatin-landscaped analyses demonstrated that BAF60b interacts with the transcription factor RUNX1 to promote the expression of CCR9 on Treg cells, which in turn affects their ability to migrate to inflammatory tissues. Our work provides insights into the essential role of BAF60b in regulating Treg cell migration and its impact on inflammatory diseases.

Vitexicarpin suppresses malignant progression of colorectal cancer through affecting c-Myc ubiquitination by targeting IMPDH2.

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer-related mortality and is characterised by extensive invasive and metastatic potential. Previous studies have shown that vitexicarpin extracted from the fruits of Vitex rotundifolia can impede tumour progression. However, the molecular mechanisms involved in CRC treatment are still not fully established. PURPOSE: Our study aimed to investigate the anticancer activity, targets, and molecular mechanisms of vitexicarpin in CRC hoping to provide novel therapies for patients with CRC. STUDY DESIGN/METHODS: The impact of vitexicarpin on CRC was assessed through various experiments including MTT, clone formation, EDU, cell cycle, and apoptosis assays, as well as a tumour xenograft model. CETSA, label-free quantitative proteomics, and Biacore were used to identify the vitexicarpin targets. WB, Co-IP, Ubiquitination assay, IF, molecular docking, MST, and cell transfection were used to investigate the mechanism of action of vitexicarpin in CRC cells. Furthermore, we analysed the expression patterns and correlation of target proteins in TCGA and GEPIA datasets and clinical samples. Finally, wound healing, Transwell, tail vein injection model, and tissue section staining were used to demonstrate the antimetastatic effect of vitexicarpin on CRC in vitro and in vivo. RESULTS: Our findings demonstrated that vitexicarpin exhibits anticancer activity by directly binding to inosine monophosphate dehydrogenase 2 (IMPDH2) and that it promotes c-Myc ubiquitination by disrupting the interaction between IMPDH2 and c-Myc, leading to epithelial-mesenchymal transition (EMT) inhibition. Vitexicarpin hinders the migration and invasion of CRC cells by reversing EMT both in vitro and in vivo. Additionally, these results were validated by the overexpression and knockdown of IMPDH2 in CRC cells. CONCLUSION: These results demonstrated that vitexicarpin regulates the interaction between IMPDH2 and c-Myc to inhibit CRC proliferation and metastasis both in vitro and in vivo. These discoveries introduce potential molecular targets for CRC treatment and shed light on new mechanisms for c-Myc regulation in tumours.

Optimizing Double-Fibril Network Morphology via Solid Additive Strategy Enables Binary All-Polymer Solar Cells with 19.50% Efficiency.

Double-fibril network morphology (DFNM), in which the donor and the acceptor can self-assemble into a double-fibril structure, is beneficial for exciton dissociation and charge transport in organic solar cells. Herein, it is demonstrated that such DFNM can be constructed and optimized in all-polymer solar cells (all-PSCs) with the assistance of 2-alkoxynaphthalene volatile solid additives. It is revealed that the incorporation of 2-alkoxynaphthalene can induce a stepwise regulation in the aggregation of donor and acceptor molecules during film casting and thermal annealing processes. Through altering the alkoxy of 2-alkoxynaphthalene solid additives, both the intermolecular interactions and molecular miscibility with the host materials can be precisely tuned, which allows for the optimization of the molecular aggregation process and facilitation of molecular self-assembly, and thus leading to reinforced molecular packing and optimized DFNM. As a result, an unprecedented efficiency of 19.50% (certified as 19.1%) is obtained for 2-ethoxynaphthalene-processed PM6:PY-DT-X all-PSCs with excellent photostability (T80 = 1750 h). This work reveals that the optimization of DFNM via solid additive strategy is a promising avenue to boosting the performance of all-PSCs.

Non B Cell-Derived Immunoglobulins in Intestinal Tract.

Intestinal epithelium constitutes a barrier to the unrestricted movement of pathogens, and other detrimental substances from the external world (gut lumen) into the interstitial environment. Intestinal epithelial cells obstruct harmful substances passing through the epithelium as a physical and chemical barrier; Moreover, the epithelial cells can express Toll-like receptors (TLRs) and cytokines to exert innate immune function. In addition, high levels of immunoglobulin A (IgA) and other antibodies exist in the intestinal mucosa, maintaining intestinal immune homeostasis in conjunction with intestinal probiotics. Traditionally, these antibodies have been deemed to be secreted by submucosal plasma cells. Nonetheless, in recent years, it has been demonstrated that intestinal epithelial cells produce a substantial amount of Igs, especially IgA or free Ig light chains, which are involved in intestinal immune homeostasis and the survival of normal epithelial cells. Furthermore, mounting evidence affirms that many human carcinoma cells, including colorectal cancer (CRC), can overexpress Igs, particularly IgG. Cancer-derived Igs exhibit a unique V(D)J rearrangement pattern distinct from B cell-derived Ig; moreover, this cancer cell-derived IgG also has a unique sialic acid modification on the 162 site of CH1 domain (SIA-IgG). The SIA-IgG plays a crucial role in promoting cancer initiation, progression, metastasis, and tumour immune escape. Simultaneously, CRC cells can also express free Ig light chains, which promote colitis, colitis-associated colon carcinogenesis, and CRC progression. Therefore, Igs expressed by CRC cells could be a potential target for diagnosing and preventing the transformation of inflammation into cancer, as well as treating CRC.

Biallelic variants in SLC26A2 cause multiple epiphyseal dysplasia-4 by disturbing chondrocyte homeostasis.

BACKGROUND: Multiple epiphyseal dysplasia-4 (MED-4, MIM 226900) is a rare autosomal recessive disease characterized by disproportionate height and early onset osteoarthritis of the lower limbs. MED-4 is caused by homozygous or compound heterozygous pathogenic variants in the SLC26A2 gene. However, the underlying pathogenic mechanisms in chondrocytes remains unknown. This study aimed to identify the pathogenic variants within a MED-4 family and explore the molecular etiology of this condition in human primary chondrocyte cells. METHODS: Clinical data were recorded and peripheral blood samples were collected for analysis. Whole exome sequencing (WES) and bioinformatic analyses were performed to determine causative variants. Wild-type SLC26A2 and corresponding mutant expression plasmids were constructed and transfected into human primary chondrocytes. The expression and subcellular distribution of SLC26A2 protein in chondrocytes were detected by immunoblotting and immunofluorescence. Effects of these variants on chondrocytes viability and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assay. Expression of genes related to cartilage homeostasis was subsequently analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: We identified two compound heterozygous variants c.1020_1022delTGT(p.Val341del) and c.1262 T > C(p.Ile421Thr) in the SLC26A2 gene in the patients. Mutant SLC26A2Val341del and SLC26A2Ile421Thr proteins were distributed in relatively few cells and were observed only within the nucleus. The viability of chondrocytes with the SLC26A2 variant group was similar to the wild-type (WT) group. However, the protein expressions of SLC26A2Val341del and SLC26A2Ile421Thr were decreased compared with SLC26A2WT. Expression levels of matrix metallopeptidase 13 (MMP13), α-1 chain of type X collagen (COL10A1), and Runt-related transcription factor 2 (RUNX2) were significantly decreased in the variant group. However, aggrecan (ACAN) expression was higher in the variant group than the WT group. CONCLUSIONS: Overall, our data demonstrate that the variants p.Val341del and p.Ile421Thr in SLC26A2 cause MED-4 and that these two variants promote chondrocyte proliferation while inhibiting chondrocyte differentiation.

Delivering Microrobots in the Musculoskeletal System.

Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy. Patients often suffer chronic pain and might eventually have to undergo end-stage surgery. Therefore, future treatments should focus on early detection and intervention of regional lesions. Microrobots have been gradually used in organisms due to their advantages of intelligent, precise and minimally invasive targeted delivery. Through the combination of control and imaging systems, microrobots with good biosafety can be delivered to the desired area for treatment. In the musculoskeletal system, microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the body. Compared to traditional biomaterial and tissue engineering strategies, active motion improves the efficiency and penetration of local targeting of cells/drugs. This review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal system. We summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.

Nonlinear relationship between serum 25-hydroxyvitamin D and lipid profile in Chinese adults.

Background: Previous studies on the liner associations between serum 25-hydroxyvitamin D [25(OH)D] levels and lipid profiles revealed ambiguous findings. The current study therefore tried to elucidate the possible non-linear associations between 25(OH)D and lipid profiles. Methods: This study involved 8,516 adult participants (aged 18-74 years, males N = 3,750, females N = 4,766) recruited from the Dalian health management cohort (DHMC). The risk (OR) for specific dyslipidemias was estimated across the serum 25(OH)D levels and the cut-off value for serum 25(OH)D were determined by using logistic regression, restricted cubic spline, and piecewise linear regression methods, adjusted for age, sex, season, and ultraviolet index. Results: In this study, a high prevalence of 25(OH)D deficiency was observed in the participants (65.05%). The level of 25(OH)D showed the inverse U-shaped correlations with the risks (ORs) of abnormal lipid profile, with inflection points observed at 23.7 ng/ml for hypercholesterolemia, 24.3 ng/ml for hypertriglyceridemia, 18.5 ng/ml for hyper-low-density lipoprotein cholesterolemia, 23.3 ng/ml for hypo-high-density lipoprotein cholesterolemia, 23.3 ng/ml for hyper-non-high-density lipoprotein cholesterol, and 24.3 ng/ml for high remnant cholesterol. The stratified analyses showed that the risk for most dyslipidemias related to deficiency of 25(OH)D was particularly increased among females aged 50-74 (except for hypertriglyceridemia, where the highest risk was among men aged 50-74 years), during winter/spring or under low/middle ultraviolet index environments. Conclusions: Nonlinear inverse U-shaped associations were observed between 25(OH)D levels and abnormal lipid profile. The risk was particularly increased among females aged 50-74, during winter/spring period or under lower ultraviolet index environments. In vitamin D deficient subjects [25(OH)D <20 ng/ml], a positive association of serum vitamin D levels with the risk for dyslipidemia was observed, which needs a further.

The predictive role of neutrophil gelatinase-associated lipocalin in coronary artery disease.

The prognosis holds significant implications for the long-term quality of life among patients suffering from coronary artery disease. However, a pressing challenge lies in the absence of reliable biomarkers that can establish a definitive correlation between these biomarkers and the prognosis of coronary artery heart disease. This review paper delves into the critical role of neutrophil gelatinase-associated lipocalin (NGAL) in predicting outcomes in coronary artery disease. It examines the influence of NGAL on various clinical manifestations, including stable angina, ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and isolated coronary artery dilation. Furthermore, this review provides recommendations aimed at enhancing the rigor and impact of future research, thereby serving as a valuable reference for subsequent studies in this domain.

Radiosensitization effect of quinoline-indole-schiff base derivative 10E on non-small cell lung cancer cells in vitro and in tumor xenografts.

Radioresistance is an inevitable obstacle in the clinical treatment of inoperable patients with non-small cell lung cancer (NSCLC). Combining treatment with radiosensitizers may improve the efficacy of radiotherapy. Previously, the quinoline derivative 10E as new exporter of Nur77 has shown superior antitumor activity in hepatocellular carcinoma. Here, we aimed to investigate the radiosensitizing activity and acting mechanisms of 10E. In vitro, A549 and H460 cells were treated with control, ionizing radiation (IR), 10E, and 10E + IR. Cell viability, apoptosis, and cycle were examined using CCK-8 and flow cytometry assays. Protein expression and localization were examined using western blotting and immunofluorescence. Tumor xenograft models were established to evaluate the radiosensitizing effect of 10E in vivo. 10E significantly inhibited cell proliferation and increased their radiosensitivity while reducing level of p-BCRA1, p-DNA-PKs, and 53BP1 involved in the DNA damage repair pathway, indicating that its radiosensitizing activity is closely associated with repressing DNA damage repair. A549 cells showed low level of Nur77 and a low response to IR but 10E-treated A549 cells showed high level of Nur77 indicating that Nur77 is a core radiosensitivity factor and 10E restores the expression of Nur77. Nur77 and Ku80 extranuclear co-localization in the 10E-treated A549 cells suggested that 10E-modulated Nur77 nuclear exportation inhibits DNA damage repair pathways and increases IR-triggered apoptosis. The combination of 10E and IR significantly inhibits tumor growth in a tumor xenograft model. Our findings suggest that 10E acts as a radiosensitizer and that combining 10E with radiotherapy may be a potential strategy for NSCLC treatment.

Overexpression of olfactory receptor 78 ameliorates brain injury in cerebral ischaemia-reperfusion rats by activating Prkaca-mediated cAMP/PKA-MAPK pathway.

Ischemic stroke is one of the main causes of disability and death. However, recanalization of occluded cerebral arteries is effective only within a very narrow time window. Therefore, it is particularly important to find neuroprotective biological targets for cerebral artery recanalization. Here, gene expression profiles of datasets GSE160500 and GSE97537 were downloaded from the GEO database, which were related to ischemic stroke in rats. Olfactory receptor 78 (Olfr78) was screened, and which highly associated with Calcium signalling pathway and MAPK pathway. Interacting protein of Olfr78, Prkaca, was predicted by STRING, and their interaction was validated by Co-IP analysis. Then, a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a neuronal cell model stimulated by oxygen-glucose deprivation/reoxygenation (OGD/R) were constructed, and the results showed that expression of Olfr78 and Prkaca was downregulated in MCAO rats and OGD/R-stimulated neurons. Overexpression of Olfr78 or Prkaca inhibited the secretion of inflammatory factors, Ca2+ overload, and OGD/R-induced neuronal apoptosis. Moreover, Overexpression of Prkaca increased protein levels of cAMP, PKA and phosphorylated p38 in OGD/R-stimulated neurons, while SB203580, a p38 inhibitor, treatment inhibited activation of the cAMP/PKA-MAPK pathway and counteracted the effect of Olfr78 overexpression on improvement of neuronal functions. Meanwhile, overexpression of Olfr78 or Prkaca markedly inhibited neuronal apoptosis and improved brain injury in MCAO/R rats. In conclusion, overexpression of Olfr78 inhibited Ca2+ overload and reduced neuronal apoptosis in MCAO/R rats by promoting Prkaca-mediated activation of the cAMP/PKA-MAPK pathway, thereby improving brain injury in cerebral ischaemia-reperfusion.

YAP1 inhibits the senescence of alveolar epithelial cells by targeting Prdx3 to alleviate pulmonary fibrosis.

The senescence of alveolar type II (AT2) cells impedes self-repair of the lung epithelium and contributes to lung injury in the setting of idiopathic pulmonary fibrosis (IPF). Yes-associated protein 1 (YAP1) is essential for cell growth and organ development; however, the role of YAP1 in AT2 cells during pulmonary fibrosis is still unclear. YAP1 expression was found to be downregulated in the AT2 cells of PF patients. Deletion of YAP1 in AT2 cells resulted in lung injury, exacerbated extracellular matrix (ECM) deposition, and worsened lung function. In contrast, overexpression of YAP1 in AT2 cells promoted alveolar regeneration, mitigated pulmonary fibrosis, and improved lung function. In addition, overexpression of YAP1 alleviated bleomycin (BLM) -induced senescence of alveolar epithelial cells both in vivo and in vitro. Moreover, YAP1 promoted the expression of peroxiredoxin 3 (Prdx3) by directly interacting with TEAD1. Forced expression of Prdx3 inhibited senescence and improved mitochondrial dysfunction in BLM-treated MLE-12 cells, whereas depletion of Prdx3 partially abrogated the protective effect of YAP1. Furthermore, overexpression of Prdx3 facilitated self-repair of the injured lung and reduced ECM deposition, while silencing Prdx3 attenuated the antifibrotic effect of YAP1. In conclusion, this study demonstrated that YAP1 alleviates lung injury and pulmonary fibrosis by regulating Prdx3 expression to improve mitochondrial dysfunction and block senescence in AT2 cells, revealing a potential novel therapeutic strategy for pulmonary fibrosis.

Screening for optimal parameters for modified pharyngeal electrical stimulation for the treatment of dysphagia after stroke in rats.

Pharyngeal electrical stimulation (PES), a novel noninvasive peripheral nerve stimulation technique, can effectively improve neurogenic dysphagia and increase the safety and effectiveness of swallowing in the clinic. However, the lack of animal models for dysphagia has limited the mechanistic research on PES, which affects its wide application. Therefore, determining optimal parameters for PES in rats is needed to enable mechanistic studies. Modified PES (mPES), which has different waves and pulse widths from PES, was used; in previous studies mPES was found to have a neurological mechanism like that of PES. A poststroke dysphagia (PSD) model was established, and rats with dysphagia were grouped into three different intensities (0.1 mA, 0.5 mA, and 1 mA) for the selection of optimal intensity and three different frequencies (1 Hz, 2 Hz, and 5 Hz) for the selection of optimal frequency based on a stimulation duration of 10 min in the clinic. A Videofluroscopic Swallow Screen (VFSS) was used to assess swallowing function in rats before and after mPES treatment. The results showed that the 1 mA group had better swallowing function (p < 0.05) than the model group. Compared with the model group, the 1 Hz and 5 Hz groups had the same improvement in swallowing function (p < 0.05). However, the increase in excitatory signals in the sensorimotor cortex was more pronounced in the 5 Hz group than in the other frequency stimulation groups (p < 0.05). Combining the clinical findings with the above results, we concluded that the optimal stimulation parameter for mPES in rats is "frequency: 5 Hz, current intensity: 1 mA for 10 min/day", which provides a basis for future basic experimental studies of mPES in animals.