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Abstract Derived from enteroendocrine cells (EECs), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are pivotal incretin hormones crucial for blood glucose regulation. Medications of GLP-1 analogs and GLP-1 receptor activators are extensively used in the treatment of type 2 diabetes (T2D) and obesity. However, there are currently no agents to stimulate endogenous incretin secretion. Here, we find the pivotal role of KCNH2 potassium channels in the regulation of incretin secretion. Co-localization of KCNH2 with incretin-secreting EECs in the intestinal epithelium of rodents highlights its significance. Gut epithelial cell-specific KCNH2 knockout in mice improves glucose tolerance and increases oral glucose-triggered GLP-1 and GIP secretion, particularly GIP. Furthermore, KCNH2-deficient primary intestinal epithelial cells exhibit heightened incretin, especially GIP secretion upon nutrient stimulation. Mechanistically, KCNH2 knockdown in EECs leads to reduced K+ currents, prolonged action potential duration, and elevated intracellular calcium levels. Finally, we found that dofetilide, a KCNH2-specific inhibitor, could promote incretin secretion in enteroendocrine STC-1 cells in vitro and in hyperglycemic mice in vivo. These findings elucidate, for the first time, the mechanism and application of KCNH2 in regulating incretin secretion by EECs. Given the therapeutic promise of GLP-1 and GIP in diabetes and obesity management, this study advances our understanding of incretin regulation, paving the way for potential incretin secretagogue therapies in the treatment of diabetes and obesity.

Abstract Background SARS-CoV-2 infection is described as asymptomatic, mild, or moderate disease in most children. SARS-CoV-2 infection related death in children and adolescents is rare according to the current reports. COVID-19 cases increased significantly in China during the omicron surge, clinical data regarding pediatric critical patients infected with the omicron variant is limited. In this study, we aim to provide an overview of the clinical characteristics and outcomes of critically ill children admitted to a national children’s medical center in Guangdong Province, China, during the outbreak of the omicron variant infection. Methods We conducted a retrospective study from November 25, 2022, to February 8, 2023, which included 63 critically ill children, under the age of 18, diagnosed with SARS-CoV-2 infection. The patients were referred from medical institutions of Guangdong province. The medical records of these patients were analyzed and summarized. Results The median age of patients was 2 years (Interquartile Range, IQR: 1.0–8.0), sex-ratio (male/female) was 1.52. 12 (19%) patients (age ≥ 3 years) were vaccinated. The median length of hospital stay was 14 days (IQR: 6.5–23) in 63 cases, and duration of fever was 5 days (IQR: 3-8.5), pediatric intensive care unit (PICU) stay was 8 days (IQR 4.0–14.0) in 57 cases. 30 (48%) cases had clear contact history with family members who were infected with SARS-CoV-2. Three children who tested positive for SARS-CoV-2 infection did not show any abnormalities on chest imaging examination. Out of the total patients, 33 (52%) had a bacterial co-infection, with Staphylococcus aureus being the most commonly detected bacterial pathogen. Our cohort exhibited respiratory and nervous system involvement as the primary features. Furthermore, fifty (79%) patients required mechanical ventilation, with a median duration of 7 days (IQR 3.75–13.0). Among these patients, 35 (56%) developed respiratory failure, 16 (25%) patients experienced a deteriorating progression of symptoms and ultimately succumbed to the illness, septic shock was the most common condition among these patients (15 cases), followed by multiple organ failure in 12 cases, and encephalopathy identified in 7 cases. Conclusion We present a case series of critically ill children infected with the SARS-CoV-2 omicron variant. While there is evidence suggesting that Omicron may cause less severe symptoms, it is important to continue striving for measures that can minimize the pathogenic impact of SARS-CoV-2 infection in children.

Abstract Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

In order to obtain good flight performance in the near-space morphing vehicle (NMV) cruise phase, this paper proposes an adaptive sliding mode backstepping control scheme based on a neural network, aiming at the reduction of elevator control efficiency and issues of uncertainties. Firstly, this paper analyzes the aerodynamic parameters of NMV in the states of winglet stretching and retracting during the cruise phase. Based on the above, the flight efficiency of NMV can be improved by retracting winglets in the level flight mode and stretching winglets in the altitude climbing mode. Secondly, an enhanced triple power reaching law (ETPRL) is proposed to ensure that the sliding mode control system can converge quickly and reduce chattering. Then, the sliding mode control based on ETPRL and backstepping control are combined to ensure the stability of the system, and adaptive control laws are developed to estimate and compensate for uncertainties. In addition, in face of the problem of reduced elevator control efficiency, the adaptive neural network is used to estimate and compensate for interference on the control channel to improve tracking accuracy and robustness of NMV. Finally, three sets of simulations verified the effectiveness of the proposed method.

Retroviral gene therapy has emerged as a promising therapeutic modality for multiple inherited and acquired human diseases. The capability of delivering curative treatment or mediating therapeutic benefits for a long-term period following a single application fundamentally distinguishes this medical intervention from traditional medicine and various lentiviral/γ-retroviral vector-mediated gene therapy products have been approved for clinical use. Continued advances in retroviral vector engineering, genomic editing, synthetic biology and immunology will broaden the medical applications of gene therapy and improve the efficacy and safety of the treatments based on genetic correction and alteration. This review will summarize the advent and clinical translation of ex vivo gene therapy, with the focus on the milestones during the exploitation of genetically engineered hematopoietic stem cells (HSCs) tackling a variety of pathological conditions which led to marketing approval. Finally, current statue and future prospects of gene editing as an alternative therapeutic approach are also discussed.

This paper is concerned with the problems of robust switching control for near-space morphing vehicles (NMVs) with a large range of parameter uncertainty and external disturbance. For this purpose, a novel linear/nonlinear active disturbance rejection switching control method for the longitudinal dynamical model of NMVs based on the type-2 fuzzy logic system is proposed. Both linear active disturbance rejection control (LADRC) and nonlinear active disturbance rejection control (NLADRC) were designed for the velocity and altitude subsystems of NMVs. Then, the stability analysis of the cascade closed-loop and switching control systems were carried out. Furthermore, a switching control strategy based on the interval type-2 fuzzy logic system was developed, and the change rules of aerodynamic parameters with Mach number and angle of attack were examined. Finally, the experimental results validated the superior switching performance of the proposed control strategy.

Abstract The development of unmanned aerial vehicle (UAVs) has gained importance in recent years for various applications like photography, inspection of infrastructure and various agricultural applications. Various researchers have carried out numerous attempts at optimisation control of UAVs and their flight range maximisation. However, a few attempts have addressed structural deformation effects on the reliability and safety of UAVs. In order to study the effect of structural deformation on the reliability and safety of UAVs under normal flight conditions, a certain type of UAV as a research object is discussed and the augmented tracking model based on the original object system by using the Lyapunov function is built up. The performance is observed in terms of rise time and overshoot and it is observed from the simulation outcomes that the system is stable at all design points in the range of 0–9000 m, providing a rise time of 10 s and zero overshoot. From this study, it is revealed that the designed controller can effectively suppress the vibration of the flexible mode while ensuring the stability and tracking performance of the UAV.

Arthropods have a broad and expanding worldwide presence and can transmit a variety of viral, bacterial, and parasite pathogens. A number of Rickettsia and Orientia species associated with ticks, fleas, lice, and mites have been detected in, or isolated from, patients with febrile illness and/or animal reservoirs throughout the world. Mosquitoes are not currently considered vectors for Rickettsia spp. pathogens to humans or to animals. In this study, we conducted a random metagenome next-generation sequencing (NGS) of 475 pools of Aedes, Culex, and Culiseta species of mosquitoes collected in Georgia from 2018 to 2019, identifying rickettsial gene sequences in 33 pools of mosquitoes. We further confirmed the findings of the Rickettsia by genus-specific quantitative PCR (qPCR) and multi-locus sequence typing (MLST). The NGS and MLST results indicate that Rickettsia spp. are closely related to Rickettsia bellii, which is not known to be pathogenic in humans. The results, together with other reports of Rickettsia spp. in mosquitoes and the susceptibility and transmissibility experiments, suggest that mosquitoes may play a role in the transmission cycle of Rickettsia spp.

Ascorbate-glutathione cycle is an important pathway for plants to scavenge reactive oxygen species (ROS) under environmental stress conditions. The objective of this study was to investigate the effects of the endophytic fungus Serendipita indica on biomass, chlorophyll concent, ROS levels, antioxidant enzyme activities, and ascorbate-glutathione cycle in white clover under ample water and water stress conditions. The results showed that 46 days of soil water stress distinctly promoted root colonization by S. indica. Under water stress, S. indica inoculation significantly promoted shoot and root biomass, total chlorophyll content, and activities of superoxide dismutases (SOD; e.g., Fe-SOD and Cu/Zn-SOD) and peroxidase in roots, coupled with a decrease in malondialdehyde content in roots. In the ascorbate-glutathione cycle of roots, S. indica also significantly increased the activity of ascorbate peroxidase and glutathione reductase activities in water-stressed white clover, along with the increase in reduced ascorbic acid and reduced/oxidized glutathione contents, thus accelerating the ascorbate-glutathione cycle in inoculated plants to scavenge more ROS (e.g., hydrogen peroxide). As a result, S. indica enhanced the tolerance of white clover in response to water stress by enhancing antioxidant enzyme activities and accelerating the ascorbate-glutathione cycle.

The stratospheric airship has important value in both commercial and military use. The altitude position control is very crucial for the airship to conduct specific missions, which is also a challenge because of both the severe relative aerodynamic mismatches and the large lag due to the quite low speed of the airship within 15 m/s. In this paper, a coordinated altitude and attitude control method was proposed to realize satisfactory altitude position control while maintaining the attitude stability by properly employing the two actuators, the propeller thrust and the elevator, in a consistent manner. In this process, the references for the vertical speed and the pitch were specified in a straightforward way of proportionating them by considering their physical characteristics and the inherent symmetrical relationship between them, which can be obtained through the kinematics. An extended disturbance observer was used to eliminate the severe aerodynamic uncertainties to symmetrically distribute the two actuator outputs by dynamically decoupling the vertical speed and the pitch angular rate loops into the two independent integrators. As a result, the explicit proportional controllers were sufficient to realize efficient command tracking. Rigorous theoretical investigation was provided to symmetrically prove the quantitative bounded property of the estimation and tracking errors. The simulation results demonstrated the effectiveness of the proposed approach, which can realize a 500-m altitude difference tracking within 200 s with less than 0.5 deg/s pitch angular rate.