A two-layer neural circuit controls fast forward locomotion in Drosophila.

Fast forward locomotion is critical for animal hunting and escaping behaviors. However, how the underlying neural circuit is wired at synaptic resolution to decide locomotion direction and speed remains poorly understood. Here, we identified in the ventral nerve cord (VNC) a set of ascending cholinergic neurons (AcNs) to be command neurons capable of initiating fast forward peristaltic locomotion in Drosophila larvae. Targeted manipulations revealed that AcNs are necessary and sufficient for fast forward locomotion. AcNs can activate their postsynaptic partners, A01j and A02j; both are interneurons with locomotory rhythmicity. Activated A01j neurons form a posterior-anteriorly descendent gradient in output activity along the VNC to launch forward locomotion from the tail. Activated A02j neurons exhibit quicker intersegmental transmission in activity that enables fast propagation of motor waves. Our work revealed a global neural mechanism that coordinately controls the launch direction and propagation speed of Drosophila locomotion, furthering the understanding of the strategy for locomotion control.

The tail segments are required by the performance but not the accomplishment of various modes of Drosophila larval locomotion.

The tail plays important roles in locomotion control in many animals. But in animals with multiple body segments, the roles of the hind body segments and corresponding innervating neurons in locomotion control are not clear. Here, using the Drosophila larva as the model animal, we investigated the roles of the posterior terminal segments in various modes of locomotion and found that they participate in all of them. In forward crawling, paralysis of the larval tail by blocking the Abdb-Gal4 labeled neurons in the posterior segments of VNC led to a slower locomotion speed but did not prevent the initiation of forward peristalsis. In backward crawling, larvae with the Abdb-Gal4 neurons inhibited were unable to generate effective displacement although waves of backward peristalsis could be initiated and persist. In head swing where the movement of the tail is not obvious, disabling the larval tail by blocking Abdb-Gal4 neurons led to increased bending amplitude upon touching the head. In the case of larval lateral rolling, larval tail paralysis by inhibition of Abdb-Gal4 neurons did not prevent the accomplishment of rolling, but resulted in slower rolling speed. Our work reveals that the contribution of Drosophila larval posterior VNC segments and corresponding body segments in the tail to locomotion is comprehensive but could be compensated at least partially by other body segments. We suggest that the decentralization in locomotion control with respect to animal body parts helps to maintain the robustness of locomotion in multi-segment animals.

Drosophila Larvae-Inspired Soft Crawling Robot with Multimodal Locomotion and Versatile Applications.

Soft crawling robots have been widely studied and applied because of their excellent environmental adaptability and flexible movement. However, most existing soft crawling robots typically exhibit a single-motion mode and lack diverse capabilities. Inspired by Drosophila larvae, this paper proposes a compact soft crawling robot (weight, 13 g; length, 165 mm; diameter, 35 mm) with multimodal locomotion (forward, turning, rolling, and twisting). Each robot module uses 4 sets of high-power-density shape memory alloy actuators, endowing it with 4 degrees of motion freedom. We analyze the mechanical characteristics of the robot modules through experiments and simulation analysis. The plug-and-play modules can be quickly assembled to meet different motion and task requirements. The soft crawling robot can be remotely operated with an external controller, showcasing multimodal motion on various material surfaces. In a narrow maze, the robot demonstrates agile movement and effective maneuvering around obstacles. In addition, leveraging the inherent bistable characteristics of the robot modules, we used the robot modules as anchoring units and installed a microcamera on the robot's head for pipeline detection. The robot completed the inspection in horizontal, vertical, curved, and branched pipelines, adjusted the camera view, and twisted a valve in the pipeline for the first time. Our research highlights the robot's superior locomotion and application capabilities, providing an innovative strategy for the development of lightweight, compact, and multifunctional soft crawling robots.

High-Speed Automated Reconstruction of Drosophila Larval Brain from Volumetric EM Data.

To uncover the relationship between neural activity and behavior, it is essential to reconstruct neural circuits. However, methods typically used for neuron reconstruction from volumetric electron microscopy (EM) dataset are often time-consuming and require extensive manual proofreading, making it difficult to reproduce in a typical laboratory setting. To address this challenge, we have developed a set of acceleration techniques that build upon the Flood Filling Network (FFN), significantly reducing the time required for this task. These techniques can be easily adapted to other similar datasets and laboratory settings. To validate our approach, we tested our pipeline on a dataset of Drosophila larval brain serial section EM images at synaptic-resolution level. Our results demonstrate that our pipeline significantly reduces the inference time compared to the FFN baseline method and greatly reduces the time required for reconstructing the 3D morphology of neurons.

Hypoglycemic Coma Caused by Methimazole-Induced Insulin Autoimmune Syndrome, a Case Study.

Islet autoimmune syndrome (IAS) is an autoimmune disease caused by high concentrations of insulin autoantibodies (IAA) in the blood. It is characterized by hyperinsulinemia and spontaneous hypoglycemia. The incidence of IAS is low, and the hypoglycemia symptom is usually mild. Hence, the severe manifestations (up to seizures and coma) are rarely reported. Here, we reported two cases of Graves' disease who developed insulin autoimmune syndrome after methimazole treatment. The patients exhibited sudden hypoglycemic coma after receiving methimazole treatment for approximately 2 or 6 months. The patients' serum glucose levels were below 2.8 mmol/L, and laboratory tests showed high levels of serum insulin and high titers of insulin autoantibodies. Patient 1 discontinued methimazole treatment and the hypoglycemic symptoms disappeared after 7 days. However, patient 2 experienced severe hypoglycemia after discontinuation of methimazole, and the patient condition improved after glucocorticoid therapy. He developed thyroid storm during the treatment, and his condition improved after receiving standard treatment procedures for thyroid storm. To the best of our knowledge, this is the first case report of IAS in Graves' disease with thyroid storm.

Association between sociodemographic status and the T2DM-related risks in China: implication for reducing T2DM disease burden.

Objective: Analyzing the association between sociodemographic status and the type 2 diabetes mellitus (T2DM)-related risks in China to reduce the disease burden of T2DM. Methods: We downloaded data from the Global Burden of Disease Study 2019 to estimate the disease burden of T2DM in China. Secondary analyses were performed by year, age, gender, summary exposure value (SEV), and sociodemographic index (SDI). Results: In China, it is estimated that 3.74 (3.44-4.10) million incidence, 90.0 (82.3-98.5) million prevalence, 168.4 (143.2-194.0) thousand deaths, and 9.6 (7.6-11.9) million DALYs occurred in 2019, showing an increase of 96.8, 156.7, 162.8, and 145.4% compared to 1990. An inverse U-shaped curve was observed for the correlations between T2DM-related burden and SDI. A heavier burden was found in males. The top four risk factors were high body mass index (HBMI), dietary risks, air pollution and tobacco. HBMI, as the key risk, accounted for half of the disease burden of T2DM in China. Lower degree of SEV and higher level of attributable T2DM-related burden could be found in main risks, meaning their critical role of them in the development and progression of T2DM. An inverse U-shaped curve could be found in the association between age-standardized incidence, mortality, DALYs rate, and SDI. Conclusion: The disease burden of T2DM has rapidly increased in China. Gender disparities, different age distributions and inconsistent socioeconomic levels all played an important role in it. The key risk was HBMI. With the improvement of socioeconomic level, the main risk factors for T2DM have changed from environmental factors to lifestyle factors. Targeted control and preventative strategies to address adjustable risk factors could put an end to this soaring burden.

Association of thyroid hormone with body fat content and lipid metabolism in euthyroid male patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: This study aimed to explore the associations of thyroid hormones with body fat content and lipid metabolism in euthyroid male patients with type 2 diabetes mellitus (T2DM). METHODS: In January 2017, a cross sectional study, 66 male patients with T2DM who met the World Health Organization diagnostic criteria of 1999 who were ≥ 18.0 years and had normal thyroid function were recruited at a tertiary hospital. The categories of thyroid hormones (free triiodothyronine [FT3], free thyroxine [FT4], and thyroid-stimulating hormone [TSH]) were divided into three groups according to tertiles of thyroid hormones. RESULTS: The mean FT3, FT4, and TSH of the patients were 2.56 pg/mL, 1.03 ng/dL, and 1.50 µIU/mL, respectively. Increased FT3 were associated with higher body mass index (BMI) (P <  0.001), body fat percentage (BFP) (P = 0.008), visceral fat content (VFC) (P = 0.019), adiponectin (P = 0.037), tumor necrosis factor alpha (TNF-α) (P <  0.001), and interleukin 6 (IL-6) (P = 0.015). There were significant differences among the different FT4 categories for BMI (P = 0.033), waist-hip ratio (WHR) (P = 0.030), low-density lipoprotein cholesterol (LDL-C) (P = 0.014), and IL-6 (P = 0.009). Increased TSH could increase the total cholesterol (TC) (P = 0.005) and high-density lipoprotein cholesterol (HDL-C) (P = 0.010). FT3 was positively correlated with BMI (r = 0.45; P <  0.001), WHR (r = 0.27; P = 0.028), BFP (r = 0.33; P = 0.007), VFC (r = 0.30; P = 0.014), adiponectin (r = 0.25; P = 0.045), TNF-α (r = 0.47; P <  0.001), and IL-6 (r = 0.32; P = 0.008). FT4 was positively correlated with HDL-C (r = 0.26; P = 0.038), LDL-C (r = 0.26; P = 0.036), and adiponectin (r = 0.28; P = 0.023). TSH was positively correlated with TC (r = 0.36; P = 0.003). CONCLUSION: This study found that the changes in thyroid hormones are associated with various body fat content and lipid metabolism in euthyroid male patients with T2DM.

Effects of huoxiangzhengqi liquid on enteric mucosal immune responses in mice with Bacillus dysenteriae and Salmonella typhimurium induced diarrhea.

AIM: To explore effects of huoxiangzhengqi liquid (HXZQ) on enteric mucosal immune responses in mice with Bacillus dysenteriae and Salmonella typhimurium induced diarrhea (BSD). METHODS: BSD was induced in Balb/c mice by oral administration with Bacillus dysenteriae and Salmonella typhimurium. HXZQ was administrated from the day of diarrhea induction at dosages of 5.21 g/kg and 0.52 g/kg, respectively. The onset of diarrhea and lasting time were recorded. Peyer's patches and peripheral lymphocytes were prepared for flow cytometry, and levels of TNF-alpha in peripheral blood and enteric tissue homogenates were determined with ELISA. Student's t test was employed for statistics. RESULTS: Mice in BSD group started showing continuous diarrhea on the day of induction until the fourth day when they were sacrificed. Diarrhea in the mice of HXZQ high and low dose groups lasted for 36 and 54 h, respectively. There were more CD4+ and CD8+ cells in peripheral blood, fewer CD4+ cells in Peyer's patches in BSD mice compared to normal mice. Fewer CD4+ and CD8+ cells was shown in the mice in HXZQ high group compared to BSD mice. In Peyer's patch, there were more CD8+ cells in mice in HXZQ high and low dose groups and more CD4+ in mice in HXZQ high group. Higher levels of TNF-alpha in peripheral blood and intestinal tissue homogenates in BSD group were observed. Mice in HXZQ high group showed decreased levels of TNF-alpha in peripheral blood and enteric tissue homogenates. CONCLUSION: The immune regulation of CD4+ and CD8+ cells in Peyer's patch and suppression of TNF-alpha levels in enteric homogenates may partially explain the effect of HXZQ on improvement of BSD.