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Abstract Background The CTNS gene mutation causes infantile nephropathic cystinosis (INC). Patients with INC develop Fanconi syndrome and chronic kidney disease (CKD) with significant bone deformations. C57BL/6 Ctns−/− mice are an animal model for studying INC. Hyperleptinaemia results from the kidney's inability to eliminate the hormone leptin in CKD. Ctns−/− mice have elevated serum leptin concentrations. Leptin regulates bone metabolism through its receptor that signals further via the hypothalamic melanocortin 4 receptor (MC4R). Leptin signalling may affect bone health in Ctns−/− mice. Methods We first defined the time course of bone abnormalities in Ctns−/− mice between 1 and 12 months of age. We used both genetic and pharmacological approaches to investigate leptin signalling in Ctns−/− mice. We generated Ctns−/−Mc4r−/− double knockout mice. Bone phenotype of Ctns−/−Mc4r−/− mice, Ctns−/− mice and wild type (WT) mice at 1, 4, and 9 months of age were compared. We then treated 12‐month‐old Ctns−/− mice and WT mice with a pegylated leptin receptor antagonist (PLA) (7 mg/kg/day, IP), a MC4R antagonist agouti‐related peptide (AgRP) (2 nmol, intracranial infusion on days 0, 3, 6, 9, 12, 15, 18, 21, 24, and 27), or vehicle (normal saline), respectively, for 28 days. Whole‐body (BMC/BMD, bone area) and femoral bone phenotype (BMC/BMD, bone area, length and failure load) of mice were measured by DXA and femoral shaft biochemical test. We also measured lean mass content by EchoMRI and muscle function (grip strength and rotarod activity) in mice. Femur protein content of JAK2 and STAT3 was measured by ELISA kits, respectively. Results Bone defects are present in Ctns−/− mice throughout its first year of life. The deletion of the Mc4r gene attenuated bone disorder in Ctns−/− mice. Femoral BMD, bone area, length, and strength (failure load) were significantly increased in 9‐month‐old Ctns−/−Mc4r−/− mice than in age‐matched Ctns−/− mice. PLA and AgRP treatment significantly increased femoral bone density (BMC/BMD) and mechanical strength in 12‐month‐old Ctns−/− mice. We adopted the pair‐feeding approach for this study to show that the protective effects of PLA or AgRP on bone phenotype are independent of their potent orexigenic effect. Furthermore, an increase in lean mass and in vivo muscle function (grip strength and rotarod activity) are associated with improvements in bone phenotype (femoral BMC/BMD and mechanical strength) in Ctns−/− mice, suggesting a muscle‐bone interplay. Decreased femur protein content of JAK2 and STAT3 was evident in Ctns−/− mice. PLA or AgRP treatment attenuated femur STAT3 content in Ctns−/− mice. Conclusions Our findings suggest a significant role for dysregulated leptin signalling in INC‐related bone disorder, either directly or potentially involving a muscle‐bone interplay. Leptin signalling blockade may represent a novel approach to treating bone disease as well as muscle wasting in INC.

Objectives To evaluate the knowledge, attitudes and practices towards diagnosing and managing paediatric sepsis among paediatric physicians and nurses.Design A cross-sectional, questionnaire-based study.Setting 21 hospitals in Hubei Province between February 2023 and March 2023.Participants Paediatric physicians and nurses.Interventions None.Primary and secondary outcome measures The questionnaire contained 35 items across four dimensions (demographic information, knowledge, attitude and practice).Results The study included 295 participants (173 women). The average knowledge, attitude and practice scores were 10.93±2.61 points (possible range, 0–20 points), 32.22±2.65 points (possible range, 7–35 points) and 36.54±5.24 points (possible range, 9–45 points), respectively. Knowledge had a direct influence on both attitude (β=0.240, 95% CI 0.136 to 0.365, p=0.009) and practice (β=0.278, 95% CI 0.084 to 0.513, p=0.010), which also indirectly influenced practice through attitude (β=0.162, 95% CI 0.078 to 0.290, p=0.007). Attitude directly influenced practice (β=0.677, 95% CI 0.384 to 0.902, p=0.025). A higher attitude score was associated with good practice (OR=1.392; 95% CI 1.231 to 1.576; p

Efficient and accurate water quality monitoring is of great significance to the development of marine resources, and Special Topic: Autonomous Underwater Vehicle (AUV) has broad application prospects in marine environmental monitoring.There are problems such as low efficiency, poor reliability, insufficient coverage and poor positioning accuracy when a single AUV performs water quality sampling tasks for ocean scalar field estimation.The multi-AUV-based cooperative localization and adaptive sampling system was proposed.Each AUV in the system broadcasted the collected sampling data to its teammates, and based on the data received, it corrected the location of itself based on the extended Kalman filter.With the collected sampling data, the AUV modeled the environmental scalar field with a Gaussian process and used a differential evolution path planner to plan its subsequent sampling path online.Simulation results showed that the proposed method effectively reduced the positioning error of AUVs, and improved the estimation accuracy of the environmental scalar field.

Abstract Objective Kawasaki disease (KD) can lead to permanent damage to coronary structures, the pathogenesis of which remains unknown. This experiment was designed to investigate whether miR‐223‐3p secreted in the serum of KD patients affects the proliferation and apoptosis of HCAECs in KD by regulating FOXP3. Methods Blood samples were collected in acute febrile phase of KD, after IVIG treatment, and from healthy controls. Transfected into HCAECs cells by synthetic FOXP3 siRNA/NC. A co‐culture system was established between HCAECs cells transfected with FOXP3 siRNA/NC and THP1 cells added with three sera. Results Compared with the control group, the expressions of miR‐223‐3p, RORγt, and Th17 in serum of KD patients were significantly upregulated, and the expressions of TGF‐β1, FOXP3 and Treg were significantly downregulated. At the same time, the levels of IL‐6, IL‐17, and IL‐23 were significantly increased, and the levels of IL‐10 and FOXP3 were significantly decreased. After IVIG treatment, the patient's above results were reversed. The serum of KD patients increased the expression of miR‐223‐3p and inhibited the expression of FOXP3 in HCAECs cells. IVIG serum is the opposite. Overexpression of miR‐223‐3p also promoted the apoptosis of HCAECs. In addition, serum from KD patients promoted apoptosis, whereas serum after IVIG treatment inhibited apoptosis. KD patient serum downregulated the expression of FOXP3, Bcl2, TGF‐β1 and IL‐10 in cells, and upregulated the expression of caspase3, Bax, IL‐17, IL‐6, and IL‐23. The opposite results were obtained with IVIG‐treated sera. Conclusion miR‐223‐3p secreted in serum of KD patients can regulate the expression of FOXP3 and affect the proliferation, apoptosis, and inflammation of cells.

Abstract Background Ctns−/− mice, a mouse model of infantile nephropathic cystinosis, exhibit hypermetabolism with adipose tissue browning and profound muscle wasting. Inflammatory cytokines such as interleukin (IL)‐1 trigger inflammatory cascades and may be an important cause for cachexia. We employed genetic and pharmacological approaches to investigate the effects of IL‐1 blockade in Ctns−/− mice. Methods We generated Ctns−/− Il1β−/− mice, and we treated Ctns−/− and wild‐type control mice with IL‐1 receptor antagonist, anakinra (2.5 mg/kg/day, IP) or saline as vehicle for 6 weeks. In each of these mouse lines, we characterized the cachexia phenotype consisting of anorexia, loss of weight, fat mass and lean mass, elevation of metabolic rate, and reduced in vivo muscle function (rotarod activity and grip strength). We quantitated energy homeostasis by measuring the protein content of uncoupling proteins (UCPs) and adenosine triphosphate in adipose tissue and skeletal muscle. We measured skeletal muscle fiber area and intramuscular fatty infiltration. We also studied expression of molecules regulating adipose tissue browning and muscle mass metabolism. Finally, we evaluated the impact of anakinra on the muscle transcriptome in Ctns−/− mice. Results Skeletal muscle expression of IL‐1β was significantly elevated in Ctns−/− mice relative to wild‐type control mice. Cachexia was completely normalized in Ctns−/− Il1β−/− mice relative to Ctns−/− mice. We showed that anakinra attenuated the cachexia phenotype in Ctns−/− mice. Anakinra normalized UCPs and adenosine triphosphate content of adipose tissue and muscle in Ctns−/− mice. Anakinra attenuated aberrant expression of beige adipose cell biomarkers (UCP‐1, CD137, Tmem26, and Tbx1) and molecules implicated in adipocyte tissue browning (Cox2/Pgf2α, Tlr2, Myd88, and Traf6) in inguinal white adipose tissue in Ctns−/− mice. Moreover, anakinra normalized gastrocnemius weight and fiber size and attenuated muscle fat infiltration in Ctns−/− mice. This was accompanied by correction of the increased muscle wasting signalling pathways (increased protein content of ERK1/2, JNK, p38 MAPK, and nuclear factor‐κB p65 and mRNA expression of Atrogin‐1 and Myostatin) and the decreased myogenesis process (decreased mRNA expression of MyoD and Myogenin) in the gastrocnemius muscle of Ctns−/− mice. Previously, we identified the top 20 differentially expressed skeletal muscle genes in Ctns−/− mice by RNAseq. Aberrant expression of these 20 genes have been implicated in muscle wasting, increased energy expenditure, and lipolysis. We showed that anakinra attenuated 12 of those top 20 differentially expressed muscle genes in Ctns−/− mice. Conclusions Anakinra may provide a targeted novel therapy for patients with infantile nephropathic cystinosis.

Abstract Cytokines such as IL-6, TNF-α and IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 nephrectomy in mice. We studied energy homeostasis in Il1β −/− /CKD, Il6 −/− /CKD and Tnfα −/− /CKD mice and compared with wild type (WT)/CKD controls. Parameters of cachexia phenotype were completely normalized in Il1β −/− /CKD mice but were only partially rescued in Il6 −/− /CKD and Tnfα −/− /CKD mice. We tested the effects of anakinra, an IL-1 receptor antagonist, on CKD-associated cachexia. WT/CKD mice were treated with anakinra (2.5 mg/kg/day, IP) or saline for 6 weeks and compared with WT/Sham controls. Anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function, and also attenuated molecular perturbations of energy homeostasis in adipose tissue and muscle in WT/CKD mice. Anakinra decreased serum and muscle expression of IL-6, TNF-α and IL-1β in WT/CKD mice. Anakinra attenuated browning of white adipose tissue in WT/CKD mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in WT/CKD mice. This was accompanied by correcting the increased muscle wasting signaling pathways while promoting the decreased myogenesis process in gastrocnemius of WT/CKD mice. We performed qPCR analysis for the top 20 differentially expressed muscle genes previously identified via RNAseq analysis in WT/CKD mice versus controls. Importantly, 17 differentially expressed muscle genes were attenuated in anakinra treated WT/CKD mice. In conclusion, IL-1 receptor antagonism may represent a novel targeted treatment for adipose tissue browning and muscle wasting in CKD.

Abstract Patients with chronic kidney disease (CKD) are often 25(OH)D3 and 1,25(OH)2D3 insufficient. We studied whether vitamin D repletion could correct aberrant adipose tissue and muscle metabolism in a mouse model of CKD-associated cachexia. Intraperitoneal administration of 25(OH)D3 and 1,25(OH)2D3 (75 μg/kg/day and 60 ng/kg/day respectively for 6 weeks) normalized serum concentrations of 25(OH)D3 and 1,25(OH)2D3 in CKD mice. Vitamin D repletion stimulated appetite, normalized weight gain, and improved fat and lean mass content in CKD mice. Vitamin D supplementation attenuated expression of key molecules involved in adipose tissue browning and ameliorated expression of thermogenic genes in adipose tissue and skeletal muscle in CKD mice. Furthermore, repletion of vitamin D improved skeletal muscle fiber size and in vivo muscle function, normalized muscle collagen content and attenuated muscle fat infiltration as well as pathogenetic molecular pathways related to muscle mass regulation in CKD mice. RNAseq analysis was performed on the gastrocnemius muscle. Ingenuity Pathway Analysis revealed that the top 12 differentially expressed genes in CKD were correlated with impaired muscle and neuron regeneration, enhanced muscle thermogenesis and fibrosis. Importantly, vitamin D repletion normalized the expression of those 12 genes in CKD mice. Vitamin D repletion may be an effective therapeutic strategy for adipose tissue browning and muscle wasting in CKD patients.

Abstract Background Ctns−/− mice, a mouse model of infantile nephropathic cystinosis, exhibit hypermetabolism with adipose tissue browning and profound muscle wasting. Ctns−/− mice are 25(OH)D3 and 1,25(OH)2D3 insufficient. We investigated whether vitamin D repletion could ameliorate adipose tissue browning and muscle wasting in Ctns−/− mice. Methods Twelve‐month‐old Ctns−/− mice and wild‐type controls were treated with 25(OH)D3 and 1,25(OH)2D3 (75 μg/kg/day and 60 ng/kg/day, respectively) or an ethylene glycol vehicle for 6 weeks. Serum chemistry and parameters of energy homeostasis were measured. We quantitated total fat mass and studied expression of molecules regulating adipose tissue browning, energy metabolism, and inflammation. We measured lean mass content, skeletal muscle fibre size, in vivo muscle function (grip strength and rotarod activity), and expression of molecules regulating muscle metabolism. We also analysed the transcriptome of skeletal muscle in Ctns−/− mice using RNAseq. Results Supplementation of 25(OH)D3 and 1,25(OH)2D3 normalized serum concentration of 25(OH)D3 and 1,25(OH)2D3 in Ctns−/− mice, respectively. Repletion of vitamin D partially or fully normalized food intake, weight gain, gain of fat, and lean mass, improved energy homeostasis, and attenuated perturbations of uncoupling proteins and adenosine triphosphate content in adipose tissue and muscle in Ctns−/− mice. Vitamin D repletion attenuated elevated expression of beige adipose cell biomarkers (UCP‐1, CD137, Tmem26, and Tbx1) as well as aberrant expression of molecules implicated in adipose tissue browning (Cox2, Pgf2α, and NF‐κB pathway) in inguinal white adipose tissue in Ctns−/− mice. Vitamin D repletion normalized skeletal muscle fibre size and improved in vivo muscle function in Ctns−/− mice. This was accompanied by correcting the increased muscle catabolic signalling (increased protein contents of IL‐1β, IL‐6, and TNF‐α as well as an increased gene expression of Murf‐2, atrogin‐1, and myostatin) and promoting the decreased muscle regeneration and myogenesis process (decreased gene expression of Igf1, Pax7, and MyoD) in skeletal muscles of Ctns−/− mice. Muscle RNAseq analysis revealed aberrant gene expression profiles associated with reduced muscle and neuron regeneration, increased energy metabolism, and fibrosis in Ctns−/− mice. Importantly, repletion of 25(OH)D3 and 1,25(OH)2D3 normalized the top 20 differentially expressed genes in Ctns−/− mice. Conclusions We report the novel findings that correction of 25(OH)D3 and 1,25(OH)2D3 insufficiency reverses cachexia and may improve quality of life by restoring muscle function in an animal model of infantile nephropathic cystinosis. Mechanistically, vitamin D repletion attenuates adipose tissue browning and muscle wasting in Ctns−/− mice via multiple cellular and molecular mechanisms.

Background: The COVID-19 pandemic is putting healthcare workers across the world in an unprecedented situation. The purpose of this study was to evaluate the levels of depression, anxiety, and stress among Hubei pediatric nurses during the COVID-19 pandemic and to analyze the potential factors associated with them. Materials and methods: A self-designed online questionnaire survey, which consisted of the demographic and selected features, the occupational protection knowledge, attitudes, and practices of COVID-19, and the Chinese version of Depression, Anxiety, and Stress Scale, were used to assess the levels of depression, anxiety, and stress among Hubei pediatric nurses during COVID-19 pandemic. The logistic regression analyses were performed to analyze the potential factors associated with depression, anxiety, and stress. Results: A total of 617 pediatric nurses were included in the survey. A considerable proportion of pediatric nurses reported symptoms of depression (95 [15.4%]), anxiety (201 [32.6%]), and stress (111 [18.0%]). Results of multivariable logistic regression analyses indicated that the good occupational protection practices (for depression: OR = 0.455, 95%CI: 0.281 to 0.739; for anxiety: OR = 0.597, 95%CI: 0.419 to 0.851; for stress: OR = 0.269, 95%CI: 0.166 to 0.438) and the personal protective equipment (PPE) meeting work requirements (for depression: OR = 0.438, 95%CI: 0.246 to 0.778; for anxiety: OR = 0.581, 95%CI: 0.352 to 0.959; for stress: OR = 0.504, 95%CI: 0.283 to 0.898) were independent protective factors against depression, anxiety, and stress, respectively. Yet, working in an isolation ward or fever clinic was an independent risk factor associated with depression, anxiety, and stress, respectively (for depression: OR = 1.809, 95%CI: 1.103 to 2.966; for anxiety: OR = 1.864, 95%CI: 1.221 to 2.846; for stress: OR = 2.974, 95%CI: 1.866 to 4.741). Having suspected or confirmed COVID-19 patients in the departments (OR = 1.554, 95%CI: 1.053 to 2.294) and coming in contact with the patient's bodily fluids or blood (OR = 1.469, 95%CI: 1.031 to 2.095) were independent risk factors for anxiety, while >3 times of training for COVID-19 related information was an independent protective factor for depression (OR = 0.592, 95%CI: 0.360 to 0.974). Moreover, >10 years of working was an independent risk factor for stress (OR = 1.678, 95%CI: 1.075 to 2.618). Conclusion: During the COVID-19 outbreak, a considerable proportion of Hubei pediatric nurses had psychological problems. The pediatric nurses endorsing the higher number of risk factors should be given special attention and necessary psychological intervention. Improving the levels of PPE so as to meet the work requirements and intensifying occupational protection practices might help safeguard pediatric nurses from depression, anxiety, and stress.

As one of the key components of aerospace power grid, the performance of on load tap changer (OLTC) of power transformer is very important. So it is necessary to realize real-time monitoring of its status. At present, there is no feasible monitoring scheme to carry out on-line monitoring and fault diagnosis for detecting faults of OLTC. The current waveform of the switching process will be abnormal due to the contact fault, the transition resistance fault, and most of the mechanical faults. This paper presents a fault diagnosis method for OLTC based on the current detection in the process of switching. Through on-line acquisition of current waveform in the switching process, empirical mode decomposition and Hilbert-Huang transform is used to calculate normalized time-frequency spectrum, and extract fault characteristic quantity, which can realize the comprehensive diagnosis of the running state of the equipment, and identify the early fault characteristics, and promote the process of the OLTC's maintenance, from regular test to condition based maintenance. Experiment results prove that the designed fault diagnosis instrument can effectively monitor the working condition of OLTC during the switching process and make effective fault diagnosis.

In this paper, we study the issue of out-of-sequence measurement (OOSM) in a multi-target scenario to improve tracking performance. The OOSM is very common in tracking systems, and it would result in performance degradation if we used it inappropriately. Thus, OOSM should be fully utilized as far as possible. To improve the performance of the tracking system and use OOSM sufficiently, firstly, the problem of OOSM is formulated. Then the classical B1 algorithm for OOSM problem of single target tracking is given. Next, the random finite set (RFS)-based Gaussian mixture probability hypothesis density (GM-PHD) is introduced. Consequently, we derived the equation for re-updating of posterior intensity with OOSM. Implementation of GM-PHD using OOSM is also given. Finally, several simulations are given, and results show that tracking performance of GM-PHD using OOSM is better than GM-PHD using in-sequence measurement (ISM), which can strongly demonstrate the effectiveness of our proposed algorithm.