Unraveling Changes of Brachial Artery Residual Stress and Its Relationship to Cardiovascular Disease Risk Factors.

Background: Arterial pressure volume index (API) offers a non-invasive measurement of brachial artery residual stress. This study investigated API distribution characteristics and correlations with cardiovascular disease risk (CVD) factors in a large Chinese population sample. Methods: This cross-sectional study surveyed a total of 7620 participants. We analyzed the relationships between API and factors influencing CVD, using regression-based stepwise backward selection and restrictive cubic spline models to express relationships as standardized beta values. Results: Multiple linear regression analysis identified many independent factors influencing API including age, sex, body mass index (BMI), pulse pressure (PP), heart rate (HR), hemoglobin, uric acid (UA), estimated glomerular filtration rate (eGFR), triglyceride (TC), and a history of hypertension. Notably, API values increased at 33 and escalated with advancing age. Increases in API were associated with rises in PP and UA increases, particularly when PP reached 60 mmHg and the UA reached 525 units. Conversely, API was found to decrease with elevated HR and eGFR. Furthermore, there was a significant inverted U-shaped relationship between API and BMI. Conclusions: This study was the first to describe API distribution characteristics in a large sample of the Chinese population, providing references for evaluating API changes in the assessment of residual stress variations in diverse diseases. Notably, API displayed a U-shaped relationship with age and was closely related to traditional CVD risk factors, underscoring its potential as a non-invasive tool for risk assessment in vascular health. Clinical Trial Registration: This research was registered with the China Clinical Trial Registration Center (Registration Number: ChiCTR2000035937).

Promotive effect of skin precursor-derived Schwann cells on brachial plexus neurotomy and motor neuron damage repair through milieu-regulating secretome.

Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP-SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.

Natural products as pharmacological modulators of mitochondrial dysfunctions for the treatment of diabetes and its complications: An update since 2010.

Diabetes, characterized as a well-known chronic metabolic syndrome, with its associated complications pose a substantial and escalating health and healthcare challenge on a global scale. Current strategies addressing diabetes are mainly symptomatic and there are fewer available curative pharmaceuticals for diabetic complications. Thus, there is an urgent need to identify novel pharmacological targets and agents. The impaired mitochondria have been associated with the etiology of diabetes and its complications, and the intervention of mitochondrial dysfunction represents an attractive breakthrough point for the treatments of diabetes and its complications. Natural products (NPs), with multicenter characteristics, multi-pharmacological activities and lower toxicity, have been caught attentions as the modulators of mitochondrial functions in the therapeutical filed of diabetes and its complications. This review mainly summarizes the recent progresses on the potential of 39 NPs and 2 plant-extracted mixtures to improve mitochondrial dysfunction against diabetes and its complications. It is expected that this work may be useful to accelerate the development of innovative drugs originated from NPs and improve upcoming therapeutics in diabetes and its complications.

Structural modification of oat protein by thermosonication combined with high pressure for O/W emulsion and model salad dressing production.

Oat protein is becoming an important ingredient in beverages and formulated foods owing to its high nutritive value and bland flavor; yet, its functionality remains largely unexplored. This study sought to enhance the surface activity of oat protein isolate (OPI) through high-intensity ultrasound (HIU; at 20 or 60 °C) combined with high pressure homogenization (HP; 30 MPa) treatments. Sonication disturbed the protein conformation and significantly improved surface hydrophobicity (19.7%) and ζ-potential (15.7%), which were further augmented by subsequent HP (P < 0.05). Confocal microscopy revealed a uniform oil droplet distribution in emulsions prepared with HIU+HP combination treated OPI, and the oil droplet size decreased up to 35.6% when compared to that of non-treated OPI emulsion (d = 1718 nm). Emulsifying activity was greater for HIU+HP than for HIU, and the viscosity followed a similar trend. Moreover, while emulsions prepared with HIU or HP treated OPI were more stable than control, the 60 °C HIU+HP combination treatment yielded the maximum stability. In corroboration, a model salad dressing prepared from HIU+HP treated OPI displayed a homogenous oil droplet distribution and an improved viscosity. Therefore, thermosonication combined with high pressure homogenization may be suitable for salad dressings and other oil-imbedded food products.

Selective Separation of Americium(III), Curium(III), and Lanthanide(III) by Aqueous and Organic Competitive Extraction.

Adding hydrophilic ligands into aqueous solutions for the selective binding of actinides(III) is acknowledged as an advanced strategy in Ln(III)/An(III) separation. In view of the recycling and radioactive waste disposal of the minor actinide, there remains an urgent need to design and develop the appropriate ligand for selective separation of An(III) from Ln(III). Herein, four novel hydrophilic ligands with hard-soft hybrid donors, derived from the pyridine and phenanthroline skeletons, were designed and synthesized as masking agents for selective complexation of An(III) in the aqueous phase. The known N,N,N',N'-tetraoctyl diglycolamide (TODGA) was used as lipophilic extractant in the organic phase for extraction of Ln(III), and a new strategy for the competitive extraction of An(III) and Ln(III) was developed based on TODGA and the above hydrophilic ligands. The optimal hydrophilic ligand of N,N'-bis(2-hydroxyethyl)-2,9-dicarboxamide-1,10-phenanthroline (2OH-DAPhen) displayed exceptional selectivity toward Am(III) over Ln(III), with the concentrations of HNO3 ranging from 0.05 to 3.0 M. The maximum separation factors were up to 1365 for Eu/Am, 417.66 for Eu/Cm, and 42.38 for La/Am. The coordination mode and bonding property of 2OH-DAPhen with Ln(III) were investigated by 1H NMR titration, UV-vis spectrophotometric titration, luminescence titration, FT-IR, ESI-HRMS analysis, and DFT calculations. The results revealed that the predominant species formed in the aqueous phase was a 1:1 ligand/metal complex. DFT calculations also confirmed that the affinity of 2OH-DAPhen for Am(III) was better than that for Eu(III). The present work using a competitive extraction strategy developed a feasible alternative method for the selective separation of trivalent actinides from lanthanides.

Adeno-associated virus-9 reverses delayed gastric emptying of solids in diabetic mice.

BACKGROUND: Gastroparesis is defined by delayed gastric emptying (GE) without obstruction. Studies suggest targeting heme oxygenase-1 (HO1) may ameliorate diabetic gastroparesis. Upregulation of HO1 expression via interleukin-10 (IL-10) in the gastric muscularis propria is associated with reversal of delayed GE in diabetic NOD mice. IL-10 activates the M2 cytoprotective phenotype of macrophages and induces expression of HO1 protein. Here, we assess delivery of HO1 by recombinant adeno-associated viruses (AAVs) in diabetic mice with delayed GE. METHODS: C57BL6 diabetic delayed GE mice were injected with 1 × 1012 vg scAAV9-cre, scAAV9-GFP, or scAAV9-HO1 particles. Changes to GE were assessed weekly utilizing our [13 C]-octanoic acid breath test. Stomach tissue was collected to assess the effect of scAAV9 treatment on Kit, NOS1, and HO1 expression. KEY RESULTS: Delayed GE returned to normal within 2 weeks of treatment in 7/12 mice receiving scAAV9-cre and in 4/5 mice that received the scAAV9-GFP, whereas mice that received scAAV9-HO1 did not respond in the same manner and had GE that took significantly longer to return to normal (6/7 mice at 4-6 weeks). Kit, NOS1, and HO1 protein expression in scAAV9-GFP-treated mice with normal GE were not significantly different compared with diabetic mice with delayed GE. CONCLUSIONS AND INFERENCES: Injection of scAAV9 into diabetic C57BL6 mice produced a biological response that resulted in acceleration of GE independently of the cargo delivered by the AAV9 vector. Further research is needed to determine whether use of AAV mediated gene transduction in the gastric muscularis propria is beneficial and warranted.

Increased arterial pressure volume index and cardiovascular risk score in China.

BACKGROUND AND OBJECTIVE: The new non-invasive arterial stiffness indices, arterial pressure volume index (API) is explored as a novel marker of residual stress in the wall of the peripheral muscular arteries at zero-stress state in clinical settings. The present study aimed to study the association of API with cardiovascular disease (CVD) risk in China (China-PAR). METHODS: According to China-PAR score, participants were divided into three groups: low risk (< 5%), medium risk (5-9.9%), and high risk (≥ 10.0%). API ≥ 31 was defined as high API, and the incidences of high API were compared. Logistic regression models were used to analyze the risk factors of high API and high risk China-PAR categories. The association between China-PAR and API was analyzed by restrictive cubic spline. RESULTS: The study included 4311 participants. After adjustments for confounding factors, high API was independent factor associated with high risk China-PAR categories, and the probability of high API was 1.366 times higher than that in normal API subjects. While, the independent factors associated with high API were BMI, blood pressure and heart rate. Furthermore, API had a significant U-shaped association with China-PAR. CVD risk was lowest with API of 19 units, the fastest increase at 26 units and the flattest starting point at 59 units. CONCLUSION: API, an indicator of arterial stiffness and residual stress, had a U-shaped association with China-PAR score and might play an important role in predicting CVD risk in Chinese natural populations.

Relationship of Arterial Stiffness and Central Hemodynamics With Cardiovascular Risk In Hypertension.

BACKGROUND: Hypertension is becoming a serious public health problem and noninvasive estimation of central hemodynamics and artery stiffness have been identified as important predictors of cardiovascular disease. METHODS: The study included 4,311 participants, both sex and aged between 20 and 79 years. Arterial velocity pulse index, arterial pressure-volume index (AVI, API, and the index of artery stiffness), central systolic blood pressure, central artery pulse pressure (CSBP, CAPP, and estimated via oscillometric blood pressure monitor), and 10-year risk score of cardiovascular disease in China (China-PAR) and Framingham cardiovascular risk score (FCVRS) were assessed at baseline. Regression model was performed to identify factors associated with high cardiovascular disease risk stratification. The relationships between CSBP, CAPP and China-PAR, and FCVRS were analyzed by restrictive cubic spline functions. RESULTS: The uncontrolled hypertension group showed the highest values of AVI, API, CSBP, and CAPP. In the regression analysis, CAPP and hypertension subtypes were identified as significant predictors of high cardiovascular risk stratification, and CAPP was strongly correlated with API in this cohort. Finally, CSBP and CAPP showed significant J-shaped relationships with China-PAR and FCVRS. CONCLUSIONS: Subjects with uncontrolled hypertension present with elevated values of CAPP, CSBP, API, AVI, China-PAR, and FCVRS scores. CAPP was independently associated with high cardiovascular risk stratification, and there was a significant J-shaped relationship with China-PAR and FCVRS that may identify people with higher cardiovascular risk.

Arterial Stiffness, Body Mass Index and Cardiovascular Disease Risk in Chinese Females at Various Ages.

Background: This study investigated the correlation in parameters of arterial stiffness and cardiovascular disease (CVD) risk on age and body mass index (BMI) in Chinese females. Methods: This cross-sectional study enrolled 2220 females. Arterial stiffness was assessed by the measurement of arterial velocity pulse index (AVI) and arterial pressure volume index (API). Individual 10-year cardiovascular risk was calculated for each patient using the Framingham cardiovascular risk score (FCVRS). Results: API and AVI had a significant J-shaped relationship with age. Beginning at the age of 30 years, the API started to increase, while after 49 years, the increase in API was even steeper. AVI increased from the age of 32 years, and increased more rapidly after 56 years. The linear association between API and BMI following adjustment for age was significant ( ß = 0.324, 95% CI 0.247-0.400, p < 0.001). In the total study cohort, FCVRS scores increased by 0.16 scores for every 1 kg/ m 2 increase in BMI and by 0.11 scores for each 1 value increase in API in the age adjusted model. Conclusions: API and BMI correlate with 10-year cardiovascular risk at various ages in females. Regardless of age, overweight females have a higher risk of increased API. Therefore API can be used for the early detection of CVD so that preventive therapy can be instituted in these high risk patients. Clinical Trial Registration: Registered on the official website of the China Clinical Trial Registration Center (20/08/2020, ChiCTR2000035937).

Effects of ultrafiltration on Co-Metal Organic Framework/pre-hydrolysis solution carbon materials for supercapacitor energy storage.

Here, a Co-Metal Organic Framework/pre-hydrolysis (Co-MOF/pre-hydrolysis) solution carbon material is prepared by a mild and environmentally-friendly hydrothermal carbonization technique using a pulping pre-hydrolysis solution as the raw material and Co-MOF as the metal dopant. The stable hollow structure provide sufficient space for particle shrinkage and expansion, while the low density and large specific surface area of the long, hairy tentacle structure provide a greater contact area for ions, which shorten the transmission path of electrons and charges. The materials exhibit excellent specific capacitance (400 F/g, 0.5 A/g) and stability (90%, 10,000 cycles). The Change of different concentration ratios in the structures significantly affect the electrochemical performance. The specific surface area of the carbon materials prepared by ultra-filtration increased, but the specific surface area decrease as ultrafiltration concentration increase. The specific capacitance decrease from 336 F/g for C-ZIF-67-1/3 volume ultrafiltration to 258 F/g for C-ZIF-67-1/5 ultrafiltration. The results indicate that energy storage by the carbon materials relied on a synergistic effect between their microporous and mesoporous structures. The micropores provide storage space for the transmission of ions, while the mesopores provide ion transport channels. The separation of large and small molecules after ultrafiltration concentration limit the ion transmission and energy storage of the pores.

In-Built Fabrication of MOF Assimilated Porous Hollow Carbon from Pre-Hydrolysate for Supercapacitor.

With the fast consumption of traditional fossil fuels and the urgent requirement for a low-carbon economy and sustainable development, supercapacitors are gaining more and more attention as a clean energy storage and conversion device. The research on electrode materials for supercapacitors has become a hot topic nowadays. An electrode material for a supercapacitor, comprising the ZIF-67 in-built carbon-based material, was prepared from a biomass pre-hydrolysate via a hydrothermal process. As a by-product of dissolving slurry, the pre-hydrolysate is rich in carbon, which is an excellent biomass resource. The utilization of pre-hydrolysate to prepare carbon energy materials could realize the high value utilization of pre-hydrolysate and the efficient energy conversion of biomass. Meanwhile, the cobalt-based MOF (such as ZIF-67), as a porous crystalline material, has the advantages of having a regular order, high specific surface area and controllable pore size, as well as good thermal and chemical stability. The addition of ZIF-67 modified the morphology and pore structure of the carbon, and the obtained samples showed outstanding electrochemical performance. One- and two-step synthetic processes generated specimens with a coral-like cross-linked structure and a new type of rough, hollow, dandelion-like structure, respectively, and the pore size was in the range of 2.0-5.0 nm, which is conducive to ion transport and charge transfer. In C2-ZIF-67, the hollow structures could effectively prevent the accumulation of the electrochemical active center, which could provide enough space for the shrinkage and expansion of particles to protect them from the interference of electrolytes and the formation of solid electrolyte interphase film layers. Additionally, the plush tentacle structure with low density and a large specific surface area could expose more active sites and a large electrolyte electrode contact area, and short electron and charge transport paths. Importantly, active, free electrons of small amounts of Co-MOF (1 wt%) could be stored and released through the redox reaction, further improving the electrical conductivity of Carbon-ZIF-67 materials in this work. Consequently, C2-ZIF-67 exhibited superior specific capacitance (400 F g-1, at 0.5 A g-1) and stability (90%, after 10,000 cycles).

Handheld versus conventional ultrasound for assessing carotid artery in routine volunteers.

AIM: Carotid ultrasound is a key tool for the diagnosis and evaluation of cardio disease, and the measurement of carotid intima-media thickness (CIMT) and hemodynamic parameters is of paramount importance for the imaging method. The aim of this study was to evaluate the feasibility and accuracy of handheld ultrasound devices for measuring carotid parameters. METHODS: We performed a carotid ultrasound on 25 participants using a handheld ultrasound device and a conventional ultrasound machine. For each participant, max and mean CIMT of common carotid artery (CCA) and peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI) of CCA, bilateral external carotid artery (ECA), internal carotid artery (ICA) and the vertebral artery were measured. Agreement and repeatability were evaluated by linear regression and Bland-Altman analysis. RESULTS: We found a good repeatability and consistent of handheld ultrasound device in measuring mean CIMT (r = 0.68, P < 0.01). Furthermore, there was a moderate to good agreement between handheld and conventional ultrasound systems in measuring max IMT, mean IMT, PSV, EDV and RI of CCA (0.73, 0.79, 0.52, 0.58 and 0.84, respectively). CONCLUSION: Handheld ultrasound devices were able to provide carotid IMT and hemodynamic parameters measurements similar to those of conventional ultrasound. Such capabilities of handheld ultrasound devices might be useful for the primary assessment of carotid in clinical work.

Comparative structural and emulsifying properties of ultrasound-treated pea (Pisum sativum L.) protein isolate and the legumin and vicilin fractions.

The structural properties, interfacial behavior, and emulsifying ability of ultrasound-treated pea protein isolate (PPI) and the legumin (11S) and vicilin (7S) globulin fractions prepared with a salt-solubilization procedure were investigated. Of the three protein groups, PPI was strongly responsive to ultrasound perturbation (20 kHz, 57-60 W·cm-2) showing the greatest solubility increase, particle size reduction, structure destabilization, and conformational change. Similar but less remarkable effects were observed on 11S globulins; 7S proteins, already highly soluble (>99%), were generally less sensitive to ultrasound. The ultrasound treatment significantly improved emulsifying activity, which resulted in greater emulsifying capacity and stronger interfacial adsorption for all protein samples. PPI exhibited the higher activity increase (70.8%) compared to approximately 30% for 11S and 7S. For both control and ultrasound treated proteins, the emulsifying capacity was in the order of 7S > 11S > PPI, inversely related to the trend of protein loading at the interface, indicating efficiency differences. The latter was attributed to emulsion clusters formed through protein-protein interaction in PPI and 11S emulsions which were visibly absent in 7S emulsions.

The Allocation Method for Personal Protective Equipment in the Emerging Infectious Disease Environment.

The COVID-19 pandemic gives humankind a lesson that the outbreak of an emerging infectious disease (EID) is sudden and uncertain. Accurately mastering its dynamics and putting forward an efficient and fair humanitarian logistics plan for personal protective equipment (PPE) remains difficult. This study examines the decision making for humanitarian logistics to answer the question that how to coordinate fairness and efficiency when facing supply-demand imbalance during humanitarian logistics planning in an EID environment. The main contributions include two aspects: (1) The victims' losses in terms of fairness and efficiency in receiving PPE are jointly explored by evaluating their bearing capacity evolution, and then a novel loss function is built to search for a reasonable compromise between fairness and efficiency. (2) A multi-objective optimization model is built, which is solved using the combined use of goal programming approach and improved branch and bound method. Finally, the practicability of the proposed model is tested by an EID case study. The potential advantages of the proposed model and improved approach are discussed.

Bicarbonate ion transport by the electrogenic Na+ /HCO3- cotransporter, NBCe1, is required for normal electrical slow-wave activity in mouse small intestine.

BACKGROUND: Normal gastrointestinal motility depends on electrical slow-wave activity generated by interstitial cells of Cajal (ICC) in the tunica muscularis of the gastrointestinal tract. A requirement for HCO3- in extracellular solutions used to record slow waves indicates a role for HCO3- transport in ICC pacemaking. The Slc4a4 gene transcript encoding the electrogenic Na+ /HCO3- cotransporter, NBCe1, is enriched in mouse small intestinal myenteric region ICC (ICC-MY) that generate slow waves. This study aimed to determine how extracellular HCO3- concentrations affect electrical activity in mouse small intestine and to determine the contribution of NBCe1 activity to these effects. METHODS: Immunohistochemistry and sharp electrode electrical recordings were used. KEY RESULTS: The NBCe1 immunoreactivity was localized to ICC-MY of the tunica muscularis. In sharp electrode electrical recordings, removal of HCO3- from extracellular solutions caused significant, reversible, depolarization of the smooth muscle and a reduction in slow-wave amplitude and frequency. In 100 mM HCO3- , the muscle hyperpolarized and slow wave amplitude and frequency increased. The effects of replacing extracellular Na+ with Li+ , an ion that does not support NBCe1 activity, were similar to, but larger than, the effects of removing HCO3- . There were no additional changes to electrical activity when HCO3- was removed from Li+ containing solutions. The Na+ /HCO3- cotransport inhibitor, S-0859 (30µM) significantly reduced the effect of removing HCO3- on electrical activity. CONCLUSIONS & INFERENCES: These studies demonstrate a major role for Na+ /HCO3- cotransport by NBCe1 in electrical activity of mouse small intestine and indicated that regulation of intracellular acid:base homeostasis contributes to generation of normal pacemaker activity in the gastrointestinal tract.

Interfacial dilatational and emulsifying properties of ultrasound-treated pea protein.

In this study, the structural, interfacial, and emulsifying properties of high-intensity ultrasound (HUS)-treated pea protein isolate (PPIUS) were investigated. HUS at 50% amplitude and 57-60 W·cm-2 for 5 min markedly improved protein solubility (by 132%), surface hydrophobicity (by 173%), and reduced particle size (by 52%). These physicochemical changes in PPIUS led to more rapid protein adsorption at the oil-water interface, improved emulsifying activity (by 18-27%) and capacity (by 11%), and enhanced emulsion physical stability. The multilayer nature, albeit less elastic, of the interfacial membrane formed by PPIUS when compared to control protein (PPIC), based on dilatational testing, contributed to the above results. Moreover, PPIUS-stabilized emulsions exhibited a tendency of being less susceptible to lipid oxidation during storage. Thus, structure-modifying HUS may be a valuable processing technology for the manufacture of pea protein-based emulsion foods.

Associative Memories via Predictive Coding.

Associative memories in the brain receive and store patterns of activity registered by the sensory neurons, and are able to retrieve them when necessary. Due to their importance in human intelligence, computational models of associative memories have been developed for several decades now. In this paper, we present a novel neural model for realizing associative memories, which is based on a hierarchical generative network that receives external stimuli via sensory neurons. It is trained using predictive coding, an error-based learning algorithm inspired by information processing in the cortex. To test the model's capabilities, we perform multiple retrieval experiments from both corrupted and incomplete data points. In an extensive comparison, we show that this new model outperforms in retrieval accuracy and robustness popular associative memory models, such as autoencoders trained via backpropagation, and modern Hopfield networks. In particular, in completing partial data points, our model achieves remarkable results on natural image datasets, such as ImageNet, with a surprisingly high accuracy, even when only a tiny fraction of pixels of the original images is presented. Our model provides a plausible framework to study learning and retrieval of memories in the brain, as it closely mimics the behavior of the hippocampus as a memory index and generative model.

Muscularis macrophages establish cell-to-cell contacts with telocytes/PDGFRα-positive cells and smooth muscle cells in the human and mouse gastrointestinal tract.

BACKGROUND AND AIM: Muscularis macrophages (MMs) not only mediate the innate immunity, but also functionally interact with cells important for gastrointestinal motility. The aim of this study was to determine the spatial relationship and types of contacts between the MMs and neighboring cells in the muscularis propria of human and mouse stomach, small intestine, and large intestine. METHODS: The distribution and morphology of MMs and their contacts with other cells were investigated by immunohistochemistry and transmission electron microscopy. KEY RESULTS: Immunohistochemistry showed variable shape and number of MMs according to their location in different portions of the muscle coat. By double labeling, a close association between MMs and neighboring cells, that is, neurons, smooth muscle cells, interstitial cells of Cajal (ICCs), telocytes (TCs)/PDGFRα-positive cells, was seen. Electron microscopy demonstrated that in the muscle layers of both animal species, MMs have similar ultrastructural features and have specialized cell-to-cell contacts with smooth muscle cells and TCs/PDGFRα-positive cells but not with ICCs and enteric neurons. CONCLUSION & INFERENCES: This study describes varying patterns of distribution of MMs between different regions of the gut, and reports the presence of distinct and extended cell-to-cell contacts between MMs and smooth muscle cells and between MMs and TCs/PDGFRα-positive cells. In contrast, MMs, although close to ICCs and nerve elements, did not make contact with them. These findings indicate specialized and variable roles for MMs in the modulation of gastrointestinal motility whose significance should be more closely investigated in normal and pathological conditions.

Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel Disease.

Recent studies emphasize the role of microbial metabolites in regulating gastrointestinal (GI) physiology through activation of host receptors, highlighting the potential for inter-kingdom signaling in treating GI disorders. In this study, we show that tryptamine, a tryptophan-derived bacterial metabolite, stimulates mucus release from goblet cells via activation of G-protein-coupled receptor (GPCR) 5-HT4R. Germ-free mice colonized with engineered Bacteroides thetaiotaomicron optimized to produce tryptamine (Trp D+) exhibit decreased weight loss and increased mucus release following dextran sodium sulfate treatment when compared with mice colonized with control B. thetaiotaomicron (Trp D-). Additional beneficial effects in preventing barrier disruption and lower disease activity index were seen only in female mice, highlighting sex-specific effects of the bacterial metabolite. This study demonstrates potential for the precise modulation of mucus release by microbially produced 5-HT4 GPCR agonist as a therapeutic strategy to treat inflammatory conditions of the GI tract.