Sympathetic nerve-enteroendocrine L cell communication modulates GLP-1 release, brain glucose utilization, and cognitive function.

Glucose homeostasis is controlled by brain-gut communications. Yet our understanding of the neuron-gut interface in the glucoregulatory system remains incomplete. Here, we find that sympathetic nerves elevate postprandial blood glucose but restrict brain glucose utilization by repressing the release of glucagon-like peptide-1 (GLP-1) from enteroendocrine L cells. Sympathetic nerves are in close apposition with the L cells. Importantly, sympathetic denervation or intestinal deletion of the adrenergic receptor α2 (Adra2a) augments postprandial GLP-1 secretion, leading to reduced blood glucose levels and increased brain glucose uptake. Conversely, sympathetic activation shows the opposite effects. At the cellular level, adrenergic signaling suppresses calcium flux to limit GLP-1 secretion upon sugar ingestion. Consequently, abrogation of adrenergic signal results in a significant improvement in learning and memory ability. Together, our results reveal a sympathetic nerve-enteroendocrine unit in constraining GLP-1 secretion, thus providing a therapeutic nexus of mobilizing endogenous GLP-1 for glucose management and cognitive improvement.

The Sympathetic-Immune Milieu in Metabolic Health and Diseases: Insights from Pancreas, Liver, Intestine, and Adipose Tissues.

Sympathetic innervation plays a crucial role in maintaining energy balance and contributes to metabolic pathophysiology. Recent evidence has begun to uncover the innervation landscape of sympathetic projections and sheds light on their important functions in metabolic activities. Additionally, the immune system has long been studied for its essential roles in metabolic health and diseases. In this review, the aim is to provide an overview of the current research progress on the sympathetic regulation of key metabolic organs, including the pancreas, liver, intestine, and adipose tissues. In particular, efforts are made to highlight the critical roles of the peripheral nervous system and its potential interplay with immune components. Overall, it is hoped to underscore the importance of studying metabolic organs from a comprehensive and interconnected perspective, which will provide valuable insights into the complex mechanisms underlying metabolic regulation and may lead to novel therapeutic strategies for metabolic diseases.

Precision roll angle measurement system based on autocollimation.

The traditional autocollimation method is widely used for small angle measurement due to its high precision and high resolution, but it cannot be used to measure the roll angle. To overcome this problem, a roll angle measurement method based on autocollimation is proposed in this paper. To achieve roll angle measurement, a transmission grating is selected to generate a pair of measurement beams, and a combined target is designed as the angle sensor. A roll angle with higher accuracy and resolution can be obtained by differential measurement, because the measurement error introduced by the beam angle drift of the light source can be effectively suppressed. A series of experiments is carried out to verify the performance of the proposed system. In the experiments, the resolution of the roll angle is better than 0.05 arcsec, and the accuracy of the system is 0.20 arcsec with a measurement range of 250 arcsec.

A three-dimensional small angle measurement system based on autocollimation method.

A laser autocollimator based on transmission grating and combined reflector is proposed to simultaneously measure a three-dimensional angle. The optical configuration of the proposed autocollimator is designed, and a mathematical model for measuring a three-dimensional angle is established. The three-dimensional angle is obtained by detecting the change in the direction of the three measurement beams generated by grating diffraction and reflected by a combined reflector. The experimental setup based on the proposed autocollimator was constructed, and a series of experiments were performed to verify the feasibility of the proposed autocollimator for precision angle measurement. The experimental results showed that the measurement resolution of three-dimensional angles is better than 0.01", with measurement repeatability of yaw, pitch, and roll angles being 0.013", 0.012", and 0.009", respectively.

Sarm1-mediated neurodegeneration within the enteric nervous system protects against local inflammation of the colon.

Axonal degeneration is one of the key features of neurodegenerative disorders. In the canonical view, axonal degeneration destructs neural connections and promotes detrimental disease defects. Here, we assessed the enteric nervous system (ENS) of the mouse, non-human primate, and human by advanced 3D imaging. We observed the profound neurodegeneration of catecholaminergic axons in human colons with ulcerative colitis, and similarly, in mouse colons during acute dextran sulfate sodium-induced colitis. However, we unexpectedly revealed that blockage of such axonal degeneration by the Sarm1 deletion in mice exacerbated the colitis condition. In contrast, pharmacologic ablation or chemogenetic inhibition of catecholaminergic axons suppressed the colon inflammation. We further showed that the catecholaminergic neurotransmitter norepinephrine exerted a pro-inflammatory function by enhancing the expression of IL-17 cytokines. Together, this study demonstrated that Sarm1-mediated neurodegeneration within the ENS mitigated local inflammation of the colon, uncovering a previously-unrecognized beneficial role of axonal degeneration in this disease context.

Deletions and duplications of 42 Y chromosomal short tandem repeats in Chinese Han population.

Genotypes of 42 Y chromosome STR (Y-STR) loci were analyzed for a sample of 1420 unrelated males and 1160 father-son pairs from a Chinese Han population. Deletions of Y-STR loci were detected at DYS389I, DYS389II, DYS437, DYS446, DYS447, DYS448, and DYS557 loci. The most common deletion occurred at DYS448 and DYS557 with a frequency of 0.0056 and 0.0035, respectively. On the other hand, duplications of alleles were observed at DYF387S1a/b, DYS385a/b, DYS460, DYS527a/b, DYS459a/b, and DYS557 loci. The DYF387S1a/b, DYS527a/b, and DYS385a/b showed the highest duplicated frequencies of 0.0148, 0.0134, and 0.0099, respectively. The Y-STRs located on palindromes significantly exhibited more deletions or duplications than those non-palindromic loci. Also, duplications were more frequent than deletions. Hence, deletions or duplications of Y-STRs related to their positions on the Y chromosome. All the 52 deleted or duplicated events occurred in the two-generation families inherited stably. Furthermore, the deletions may show the Chinese Han population specificity, but the duplications may not have a similar phenomenon. Our results will be helpful to correct interpretation of the genetic profile of Y-STR loci in forensic casework.

Parallel beam generation method for a high-precision roll angle measurement with a long working distance.

A novel measurement system for a high-precision roll angle measurement of long working distance on the basis of two parallel beams in association with two detectors is presented. The measurement system consists of a light source part and a detecting part. The light source part uses transmission grating and a plane mirror to produce a pair of high-precision parallel beams. The nonparallelism of the dual beam caused by the installation error can be compressed to ensure the measurement system achieves high-precision measurement and long working distance. The effectiveness of the measurement system and proposed methods are demonstrated by a series of experiments. The resolution of 0.5'' and measurement accuracy of 1.1'' can be obtained by the set-up measurement system.

Identification of a small RNA that directly controls the translation of the quorum sensing signal synthase gene rhlI in Pseudomonas aeruginosa.

The biofilm formation by Pseudomonas aeruginosa highly increases the bacterial resistance to antimicrobial agents and host immune clearance. The biofilm formation is positively regulated by two small RNAs, RsmY and RsmZ. Previously, we reported that mutation in the polynucleotide phosphorylase (PNPase) coding gene pnp increases the levels of RsmY/Z. However, in this study, we found that the biofilm formation is decreased in the pnp mutant, which is due to a defect in rhamnolipids production. The rhamnolipids production is regulated by the RhlI-RhlR quorum sensing system. We found that PNPase influences the translation of RhlI through its 5'-untranslated region (UTR) and identified that the sRNA P27 is responsible for the translational repression. In vitro translation experiments demonstrated that P27 directly represses the translation of the rhlI mRNA through its 5'UTR in an Hfq-dependent manner. Point mutations in the rhlI 5'UTR or P27, which abolish the pairing between the two RNAs restore the rhlI expression and rhamnolipids production as well as the biofilm formation in the pnp mutant. Overall, our results reveal a novel layer of regulation of the Rhl quorum sensing system by the sRNA P27.

Pseudomonas aeruginosa quorum-sensing metabolite induces host immune cell death through cell surface lipid domain dissolution.

Bacterial quorum-sensing autoinducers are small chemicals released to control microbial community behaviours. N-(3-oxo-dodecanoyl) homoserine lactone, the autoinducer of the Pseudomonas aeruginosa LasI-LasR circuitry, triggers significant cell death in lymphocytes. We found that this molecule is incorporated into the mammalian plasma membrane and induces dissolution of eukaryotic lipid domains. This event expels tumour necrosis factor receptor 1 into the disordered lipid phase for its spontaneous trimerization without its ligand and drives caspase 3-caspase 8-mediated apoptosis. In vivo, P. aeruginosa releases N-(3-oxo-dodecanoyl) homoserine lactone to suppress host immunity for its own better survival; conversely, blockage of caspases strongly reduces the severity of the infection. This work reveals an unknown communication method between microorganisms and the mammalian host and suggests interventions of bacterial infections by intercepting quorum-sensing signalling.