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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.

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).

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.

Abstract 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 (

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.

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 (β = 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/m2 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).

Summary: 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.

Extrapancreatic nerves project to pancreatic islets directly or converge onto intrapancreatic ganglia. Intrapancreatic ganglia constitute a complex information-processing center that contains various neurotransmitters and forms an endogenous neural network. Both intrapancreatic ganglia and extrapancreatic nerves have an important influence on pancreatic endocrine function. This review introduces the histomorphology, innervation, neurochemistry, and electrophysiological properties of intrapancreatic ganglia/neurons, and summarizes the modulatory effects of intrapancreatic ganglia and extrapancreatic nerves on endocrine function.

Background & Aims: Gastroparesis is a complication of diabetes characterized by delayed emptying of stomach contents and accompanied by early satiety, nausea, vomiting, and pain. No safe and reliable treatments are available. Interleukin 10 (IL10) activates the M2 cytoprotective phenotype of macrophages and induces expression of heme oxygenase 1 (HO1) protein. We investigated whether IL10 administration could improve gastric emptying and reverse the associated cellular and electrical abnormalities in diabetic mice. Methods: Nonobese diabetic mice with delayed gastric emptying were given either IL10 (0.1â1 μg, twice/day) or vehicle (controls). Stomach tissues were isolated, and sharp microelectrode recordings were made of the electrical activity in the gastric muscle layers. Changes to interstitial cells of Cajal (ICC), reduced nicotinamide adenine dinucleotide phosphate diaphorase, and levels and distribution of HO1 protein were determined by histochemical and imaging analyses of the same tissues. Results: Gastric emptying remained delayed in vehicle-treated diabetic mice but returned to normal in mice given IL10 (n = 10 mice; P < .05). In mice given IL10, normalization of gastric emptying was associated with a membrane potential difference between the proximal and distal stomach, and lower irregularity and higher frequency of slow-wave activity, particularly in the distal stomach. Levels of HO1 protein were higher in stomach tissues from mice given IL10, and ICC networks were more organized, better connected, and more evenly distributed compared with controls. Conclusions: IL10 increases gastric emptying in diabetic mice and has therapeutic potential for patients with diabetic gastroparesis. This response is associated with up-regulation of HO1 and repair of connectivity of ICC networks. Keywords: Alternatively Activated Macrophages, Heme Oxygenase 1, Electrical Slow Wave

Purpose: The pancreas is innervated by sensory nerves, parasympathetic and sympathetic nerves. The classical neurotransmitters, acetylcholine and noradrenaline, and some kind of neuropeptides are contained in the terminals of these nerves. Neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) co-released from the primary sensory fibers have been identified as the key neurotransmitters in pancreas. Pancreatic ductal epithelium cells are one of the important sources of the pancreatic islet β-cell neogenesis. We hypothesized that SP and CGRP might play a role on proliferation of ductal cells and differentiation of ductal cells toward the β-cell neogenesis.Methods: Primary ductal cells of rat pancreas at the third passage (P3) were used. The identification of P3 cells were confirmed with flow cytometry analysis and immunostaining by CK19 (the ductal cell marker). Proliferation of ductal cells was verified by CCK-8 assay and Ki67 immunostaining. Differentiation of ductal cells was determined with immunostaining and flow cytometry. Possible mechanism was explored by testing the key proteins of Wnt signaling using Western blot analysis.Results: Our data showed that SP but not CGRP promoted proliferation of ductal cells. Moreover, NK-1 receptor antagonist L-703,606 blocked the SP-induced stimulation of proliferation. The results of Western blot analysis showed that L-703,606 attenuated the effects of substance P on NK1R, GSK-3β, and β-catenin expression. However, SP did not directly induce the differentiation of ductal cells into β-cells, and did not promote the progression of ductal cells to differentiate into more insulin-produced cells in induction medium.Conclusions: These findings suggested that SP but not CGRP promoted proliferation of adult pancreatic ductal cells. SP promoted proliferation of ductal cells but not differentiation into β-cells. NK1R and Wnt signaling pathway might be involved in the mechanism of promoting the proliferation of ductal cells by SP. Findings in this study indicated the lack of SP might be a possible indicator for the initial of diabetes. SP could also be used as a drug candidate for the treatment of diabetes.

The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c‐FOS/c‐JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine‐pre‐treated macrophage or Bafilomycin A1 (an autophagy inhibitor)‐pre‐treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK‐glutamine‐autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction. [ABSTRACT FROM AUTHOR]

The southeast edge of the Loess Plateau (SELP) is a crucial area for studying subsistence strategies and social complexity in prehistoric China. Currently, no systematic isotopic study has been conducted to reveal shifts in subsistence strategies and their link to the trajectory of social complexity. This paper compiles previously published isotopic data from human and fauna bones at 24 sites dating from 8000 to 5000 BP, aiming to uncover diachronic changes in subsistence strategies and their relationship with social complexity. The results indicate a gradual increase in millet consumption by humans and an increasing utilization of millet‐based byproducts as feed for domestic animals (pigs and dogs) over time. The isotopic data of humans and animals demonstrate the establishment of millet agriculture during the Early Yangshao period (7000–6000 BP). Millet agriculture creates a crucial material foundation for population growth and cultural prosperity. Two modes of millet cultivation, intensive and extensive, are proposed to explain the continuous development of millet agriculture since the Early Yangshao period. Finally, significant dietary heterogeneity among the human population during the Late Yangshao period strongly suggests the emergence of social differentiation and complexity, supported by other archaeological evidence such as settlement hierarchies and the presence of exquisite objects in burials. [ABSTRACT FROM AUTHOR]

Objective: To evaluate accuracy and feasibility of a handheld ultrasound machine for measuring carotid artery intima-media thicknesses (CIMT) and hemodynamic parameters by different expertise levels of ultrasound operators. Methods: : The operators were divided into three groups based on the level of their medical expertise: ultrasound technician, sonographer, and nursing staff. Operators from each group measured the CIMT and hemodynamic parameters of 25 volunteers using both handheld ultrasound and a conventional ultrasound machine. The reliability and reproducibility of handheld ultrasound measurements of CIMT and hemodynamic parameters (peak systolic velocity (PSV), end-diastolic velocity (EDV)) in operators were analyzed. Results: After a period of training, there was no statistically significant difference between the mean CIMT measured using handheld ultrasound among the three operators (0.45 ± 0.09 mm, 0.50 ± 0.07 mm, 0.46 ± 0.08 mm, P > 0.05, respectively), as well as PSV (83.30 ± 15.42 cm/s, 76.28 ± 13.26 cm/s, 81.12 ± 21.21 cm/s, P > 0.05, respectively) and EDV (21.04 ± 4.12 cm/s, 21.87 ± 5.05 cm/s, 20.17 ± 5.90 cm/s, respectively, P > 0.05). Furthermore, there was a good repeatability and consistent of handheld ultrasound device in measuring mean CIMT in the ultrasound technician and sonographer groups (r = 0.662, 0.691, respectively, P < 0.01). Conclusions: Under the premise of proper training, handheld ultrasound systems are feasible for rapid and primary assessment of carotid artery by operators with different levels of expertise. [ABSTRACT FROM AUTHOR]