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Abstract Quantifying emesis in Suncus murinus (S. murinus) has traditionally relied on direct observation or reviewing recorded behaviour, which are laborious, time-consuming processes that are susceptible to operator error. With rapid advancements in deep learning, automated animal behaviour quantification tools with high accuracy have emerged. In this study, we pioneere the use of both three-dimensional convolutional neural networks and self-attention mechanisms to develop the Automatic Emesis Detection (AED) tool for the quantification of emesis in S. murinus, achieving an overall accuracy of 98.92%. Specifically, we use motion-induced emesis videos as training datasets, with validation results demonstrating an accuracy of 99.42% for motion-induced emesis. In our model generalisation and application studies, we assess the AED tool using various emetics, including resiniferatoxin, nicotine, copper sulphate, naloxone, U46619, cyclophosphamide, exendin-4, and cisplatin. The prediction accuracies for these emetics are 97.10%, 100%, 100%, 97.10%, 98.97%, 96.93%, 98.91%, and 98.41%, respectively. In conclusion, employing deep learning-based automatic analysis improves efficiency and accuracy and mitigates human bias and errors. Our study provides valuable insights into the development of deep learning neural network models aimed at automating the analysis of various behaviours in S. murinus, with potential applications in preclinical research and drug development.

Contactors are extensively utilized in the control field. Enhancing the response speed and reducing mechanical tremors during switching-in hold great significance in improving contactor’s reliability. A novel A.C. contactor suitable for low-voltage environments has been developed based on the unique properties of the magnetic shape memory alloy (MSMA). It exhibited remarkable characteristics such as large dependent variables, fast response speed, and strong controllability. First, the magnetron characteristics of the MSMA were introduced. Then, the overall structure of the new contactor was designed based on the MSMA output characteristics and the contactor’s design requirements. Next, switching-in characteristics of the contactor under the drive signal were analyzed through simulation. Finally, an experimental measurement was carried out to test the performance of the prototype contactor during separating brake and switching in. The A.C. contactor driven by the MSMA could achieve a response speed of 9.8 ms. The contact movement in the switching process is smooth, which effectively avoids the occurrence of contact bounce in the closing process, which provides theoretical support for the development of the MSMA in the field of low-voltage electrical control application research.

Abstract Background Pro-opiomelanocortin (POMC) neurons play a sexually dimorphic role in body weight and glucose balance. However, the mechanisms for the sex differences in POMC neuron functions are not fully understood. Results We detected small conductance calcium-activated potassium (SK) current in POMC neurons. Secondary analysis of published single-cell RNA-Seq data showed that POMC neurons abundantly express SK3, one SK channel subunit. To test whether SK3 in POMC neurons regulates POMC neuron functions on energy and glucose homeostasis, we used a Cre-loxP strategy to delete SK3 specifically from mature POMC neurons. POMC-specific deletion of SK3 did not affect body weight in either male or female mice. Interestingly, male mutant mice showed not only decreased food intake but also decreased physical activity, resulting in unchanged body weight. Further, POMC-specific SK3 deficiency impaired glucose balance specifically in female mice but not in male mice. Finally, no sex differences were detected in the expression of SK3 and SK current in total POMC neurons. However, we found higher SK current but lower SK3 positive neuron population in male POMC neurons co-expressing estrogen receptor α (ERα) compared to that in females. Conclusion These results revealed a sexually dimorphic role of SK3 in POMC neurons in both energy and glucose homeostasis independent of body weight control, which was associated with the sex difference of SK current in a subpopulation of POMC + ERα + neurons.

Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons — namely, glucose-inhibited (GI) neurons — paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood glucose and impaired counterregulatory responses during hypoglycemia in mice. Activation of VMHAno4 neurons increased food intake and blood glucose, while chronic inhibition of VMHAno4 neurons ameliorated hyperglycemia in a type 1 diabetic mouse model. Finally, we showed that VMHAno4 neurons represent a unique orexigenic VMH population and transmit a positive valence, while stimulation of neurons that do not express Ano4 in the VMH (VMHnon-Ano4) suppress feeding and transmit a negative valence. Together, our results indicate that the Ano4 channel and VMHAno4 neurons are potential therapeutic targets for human diseases with abnormal feeding behavior or glucose imbalance.

Abstract The brain, particularly the ventromedial hypothalamic nucleus (VMH), has been long known for its involvement in glucose sensing and whole-body glucose homeostasis. However, it is still not fully understood how the brain detects and responds to the changes in the circulating glucose levels, as well as brain-body coordinated control of glucose homeostasis. In this review, we address the growing evidence implicating the brain in glucose homeostasis, especially in the contexts of hypoglycemia and diabetes. In addition to neurons, we emphasize the potential roles played by non-neuronal cells, as well as extracellular matrix in the hypothalamus in whole-body glucose homeostasis. Further, we review the ionic mechanisms by which glucose-sensing neurons sense fluctuations of ambient glucose levels. We also introduce the significant implications of heterogeneous neurons in the VMH upon glucose sensing and whole-body glucose homeostasis, in which sex difference is also addressed. Meanwhile, research gaps have also been identified, which necessities further mechanistic studies in future.

Pro-opiomelanocortin (POMC) neurons are important for the regulation of body weight and glucose balance. The inhibitory tone to POMC neurons is mediated primarily by the GABA receptors. However, the detailed mechanisms and functions of GABA receptors are not well understood. The α5 subunit of GABAA receptor, Gabra5, is reported to regulate feeding, and we found that Gabra5 is highly expressed in POMC neurons. To explore the function of Gabra5 in POMC neurons, we knocked down Gabra5 specifically from mature hypothalamic POMC neurons using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 strategy. This POMC-specific knock-down of Gabra5 did not affect body weight or food intake in either male or female mice. Interestingly, the loss of Gabra5 caused significant increases in the firing frequency and resting membrane potential, and a decrease in the amplitude of the miniature inhibitory postsynaptic current (mIPSC) in male POMC neurons. However, the loss of Gabra5 only modestly decreased the frequency of mIPSC in female POMC neurons. Consistently, POMC-specific knock-down of Gabra5 significantly improved glucose tolerance in male mice but not in female mice. These results revealed a sexually dimorphic role of Gabra5 in POMC neuron activity and glucose balance, independent of body weight control.

Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of chemotherapeutic drugs improved the survival of cancer patients, these drugs are notorious for causing many severe side effects that significantly reduce the efficacy of anti-cancer treatment and patients’ quality of life. Many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide analogs may cause direct and indirect neurotoxicity. In this review we discuss the main effects of chemotherapy on the peripheral and central nervous systems, including neuropathic pain, chemobrain, enteric neuropathy, as well as nausea and emesis. Understanding mechanisms involved in chemotherapy-induced neurotoxicity is crucial for the development of drugs that can protect the nervous system, reduce symptoms experienced by millions of patients, and improve the outcome of the treatment and patients’ quality of life.

The shape estimation technique can help solve the end positioning or grasping control of soft robots. However, there is a lack of sensing and modeling techniques for accurate deformation estimation and soft robots with axial elongation, e.g., pneumatic soft actuators (PSAs). This paper presents a shape-self-sensing pneumatic soft actuator (SPSA) with integrated liquid-metal piecewise curvature sensors (LMCSs). Two types of LM composite (Ga-In-Sn/Ga2O3 composites for the sensor and Ga-In-Sn/NdFeB/Ni for the electronic wire) were used to build the strain sensor network. Furthermore, a piecewise variable curvature (PVC) model was developed to predict the bending deformation of the soft actuator. A two-SPSAs-based gripper was built to test the identification performance of LMCSs. The results indicate that SPSA could perform contact and size identification using the PVC model. In addition, the K-nearest neighbors (KNN) algorithm was used to classify the shape of the targets. Finally, the circular, triangular, and square targets were identified with an accuracy rate of 93.3%. The work was expected to be applied to the size and shape perception and deformation planning of soft robots. [ABSTRACT FROM AUTHOR]

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb5-HTDRN circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a lightresponsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice. [ABSTRACT FROM AUTHOR]

The major female ovarian hormone, 17ß-estradiol (E2), can alter neuronal excitability within milliseconds to regulate a variety of physiological processes. Estrogen receptor-a (ERa), classically known as a nuclear receptor, exists as a membrane-bound receptor to mediate this rapid action of E2, but the ionic mechanisms remain unclear. Here, we show that a membrane channel protein, chloride intracellular channel protein-1 (Clic1), can physically interact with ERa with a preference to the membrane-bound ERa. Clic1-mediated currents can be enhanced by E2 and reduced by its depletion. In addition, Clic1 currents are required to mediate the E2-induced rapid excitations in multiple brain ERa populations. Further, genetic disruption of Clic1 in hypothalamic ERa neurons blunts the regulations of E2 on female body weight balance. In conclusion, we identified the Clic1 chloride channel as a key mediator for E2-induced rapid neuronal excitation, which may have a broad impact on multiple neurobiological processes regulated by E2. [ABSTRACT FROM AUTHOR]

Declined memory is a hallmark of Alzheimer's disease (AD). Experiments in rodents and human postmortem studies suggest that serotonin (5-hydroxytryptamine, 5-HT) plays a role in memory, but the underlying mechanisms are unknown. Here, we investigate the role of 5-HT 2C receptor (5-HT2CR) in regulating memory. Transgenic mice expressing a humanized HTR2C mutation exhibit impaired plasticity of hippocampal ventral CA1 (vCA1) neurons and reduced memory. Further, 5-HT neurons project to and synapse onto vCA1 neurons. Disruption of 5-HT synthesis in vCA1-projecting neurons or deletion of 5-HT2CRs in the vCA1 impairs neural plasticity and memory. We show that a selective 5-HT2CR agonist, lorcaserin, improves synaptic plasticity and memory in an AD mouse model. Cumulatively, we demonstrate that hippocampal 5-HT2CR signaling regulates memory, which may inform the use of 5-HT2CR agonists in the treatment of dementia. [ABSTRACT FROM AUTHOR]