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Abstract Urocortin 2 (UCN2) acts as a ligand for the G protein-coupled receptor corticotropin-releasing hormone receptor 2 (CRHR2). UCN2 has been reported to improve or worsen insulin sensitivity and glucose tolerance in vivo. Here we show that acute dosing of UCN2 induces systemic insulin resistance in male mice and skeletal muscle. Inversely, chronic elevation of UCN2 by injection with adenovirus encoding UCN2 resolves metabolic complications, improving glucose tolerance. CRHR2 recruits Gs in response to low concentrations of UCN2, as well as Gi and β-Arrestin at high concentrations of UCN2. Pre-treating cells and skeletal muscle ex vivo with UCN2 leads to internalization of CRHR2, dampened ligand-dependent increases in cAMP, and blunted reductions in insulin signaling. These results provide mechanistic insights into how UCN2 regulates insulin sensitivity and glucose metabolism in skeletal muscle and in vivo. Importantly, a working model was derived from these results that unifies the contradictory metabolic effects of UCN2.

Abstract Background Patients are recommended not to drive for at least the first 24 h after endoscopy with propofol sedation. However, the evidence underlying these recommendations is scarce. We hypothesized that after endoscopic procedures performed under propofol sedation, the subject’s driving ability was restored in less than 24 h. Methods We prospectively enrolled thirty patients between 20 and 70 years possessing a legitimate driver’s license scheduled for endoscopy at our hospital. The sample chosen was a convenience sample. Gastroscopy or colonoscopy was performed with propofol sedation. Before and after endoscopy, the investigator drove the subjects to the laboratory to assess their driving skills using a driving simulation system, which employs 3 driving scenarios designed by professional transportation researchers. The blood propofol concentration was estimated before endoscopy, and 2 and 4 h after endoscopy. The primary outcome was the time required for subjects to recover their driving ability after propofol sedation. The secondary outcome was the blood propofol concentration before and after endoscopic procedures under propofol anesthesia. Results Thirty volunteers participated in the study and 18 of them completed all the interventions. In the low-risk S-curve scene, the mean acceleration, lane deviation, and number of deviations from the path at baseline (0.016 cm/s2, 42.50 cm, and 0.83, respectively) were significantly less than that at post-2 h (0.029 cm/s2, P = 0.001; 53.80 cm, P = 0.014; 2.06, P = 0.022). In the moderate-(overtaking) and high-risk (emergency collision avoidance) scenes, the tested parameters at baseline and post-2 h were statistically comparable. In the low-, moderate-, and high-risk scenes the tested parameters at baseline and post-4 h were statistically comparable. The total range of propofol was 120-280 mg.The mean blood concentration of propofol at post-2 h was 0.81 ± 0.40 µg/mL, and at post-4 h was below the limit of detection. Conclusion After endoscopy performed under propofol sedation, subjects’ driving abilities were completely restored at 4 h when tested on a simulator.

Abstract This study examined the physiological effects of replacing some of the casein with either a plant based, animal or combination of protein sources in a high-fat diet fed to golden Syrian hamsters. Cooked kidney beans (BN) and beef (Bf) patties drained of fat were fed at 25 and 50% of diet. A combination of BN and Bf (BNBf) was also fed at 25 and 50%. Saturated fat content of the 25% Bf (Bf25) and 50% Bf (Bf50) increased 57 and 215% compared to Control. The Bf diets also increased caloric density compared to the Control. Likewise, the 50% Bn (Bn50) diet had 60% less saturated fat and lower caloric density than the Control. Despite these differences there were no differences in body weight gain or adipose weight between BN of Bf diets and Control. The BN50 diet reduced liver weight and increased caloric intake. The BN diets reduced total plasma cholesterol (TC). The BF diets also reduced TC but the results were not significant. The BN25, BN50 and BNBF50 diets also reduced low density lipoprotein (LDL) cholesterol. The BN and BF50 diets reduced liver fat. The BN diets decreased fecal fat excretion while the BF diets increased excretion. This suggests that increased fat excretion might offset the higher total fat and saturated fat of the BF diets to reduce adverse effects on body weight, adipose weight, and cholesterol. The high-fat content of the base (Control) diet may have muted the effects of the diet treatments. Graphical Abstract

Objectives: This study aimed to investigate the microbiological characteristics, antimicrobial resistance profiles, antibiotic choice, and outcomes of Nocardia infection in various centers over a 7-year period (from 2015 to 2021). Methods: We retrospectively analyzed the medical records of all hospitalized patients diagnosed with Nocardia between 2015 and 2021. The isolates were identified to the species level through the sequencing of 16S ribosomal RNA or secA1 or ropB genes. The susceptibility profiles were determined using the broth microdilution method. Results: Of the 130 nocardiosis cases, 99 (76.2%) were established as pulmonary infection, of which the most common underlying disease was chronic lung disease (40.4%, 40/99), including bronchiectasis, chronic obstructive pulmonary disease, and chronic bronchitis. Among 130 isolates, 12 species were identified, with the most common species being Nocardia cyriacigeorgica (37.7%) and Nocardia farcinica (20.8%). All Nocardia strains were susceptible to linezolid and amikacin, and the susceptibility rate of trimethoprim-sulfamethoxazole (TMP-SMX) was 97.7%. Of the 130 patients, 86 (66.2%) received TMP-SMX monotherapy or multidrug regimen. Furthermore, 92.3% patients who were treated achieved clinical improvement. Conclusion: TMP-SMX was the treatment of choice for nocardiosis, and other combination drugs with TMP-SMX therapy yielded even better results.

Excessive extracellular matrix (ECM) deposition is a defining feature of cardiac fibrosis. Most notably, it is characterized by a significant change in the concentration and volume fraction of collagen I, a disproportionate deposition of collagen subtypes, and a disturbed ECM network arrangement, which directly affect the systolic and diastolic functions of the heart. Immune cells that reside within or infiltrate the myocardium, including macrophages, play important roles in fibroblast activation and consequent ECM remodeling. Through both direct and indirect connections to fibroblasts, monocyte-derived macrophages and resident cardiac macrophages play complex, bidirectional, regulatory roles in cardiac fibrosis. In this review, we discuss emerging interactions between fibroblasts and macrophages in physiology and pathologic conditions, providing insights for future research aimed at targeting macrophages to combat cardiac fibrosis.

We introduced a terminal alkyne into the core structure of dolutegravir, resulting in the synthesis of 34 novel dolutegravir-1,2,3-triazole compounds through click chemistry. These compounds exhibited remarkable inhibitory activities against two hepatocellular carcinoma cell lines, Huh7 and HepG2. Notably, compounds 5e and 5p demonstrated exceptional efficacy, particularly against Huh7 cells, with IC50 values of 2.64 and 5.42 μM. Additionally, both compounds induced apoptosis in Huh7 cells, suppressed tumor cell clone formation, and elevated reactive oxygen species (ROS) levels, further promoting tumor cell apoptosis. Furthermore, compounds 5e and 5p activated the LC3 signaling pathway, inducing autophagy, and triggered the γ-H2AX signaling pathway, resulting in DNA damage in tumor cells. Compound 5e exhibited low toxicity, highlighting its potential as a promising anti-tumor drug.

It is important to elaborate on versatile strategies for achieving the perfect nonreciprocal reflection amplification, which is the key technology of high-quality nonreciprocal photonic devices. In this work, we ingeniously design a coherent four-level N-type atomic system to harness the nonreciprocal light amplification, in which the uniform distribution of atoms is driven by two strong coupling fields and a weak probe field. In our regime, the strength of the two control fields is designed with linear variation along the x direction to destroy the spatial symmetry of the probe susceptibility, leading to the nonreciprocity of the reflection. In particular, the closed-loop transitions to amplify the probe field are due to the combined effect of the control fields and spontaneous emissions. The numerical simulation indicates that the perfect nonreciprocal reflection amplification can be realized and modulated by the appropriate settings of the control fields and the detuning, Δc. Our results will open a new route toward harnessing nonreciprocity, which can provide more convenience and possibilities in experimental realization.

The introduction of a dynamic model in robot trajectory tracking control design can significantly improve its trajectory tracking accuracy, but there are many uncertainties in the robot dynamic model which can be dealt with through robust control and adaptive control. The prevailing robust control as well as adaptive control methods require real-time computation of robot dynamics, but the extreme complexity of the robot dynamics equations makes it difficult to apply these methods in real industrial systems. To this end, this article proposes a robust adaptive control method based on the desired trajectory, which uses the desired trajectory to compute most of the control terms offline, including the robot’s nominal dynamics and regression matrices, and substantially reduces the need for real-time computation of the feedback signals. The robust term modifies the perturbation of the inertial parameters of the links, the adaptive term learns the friction coefficients of the joints online, and an additional compensation term is designed to satisfy the Lyapunov stability condition of the system. Finally, taking a universal manipulator as the experimental platform, the control performances of different control methods are compared to show the feasibility of the controller and the effective reduction in real-time computational complexity.

Soil heavy metal pollution poses a formidable challenge for environmental protection professionals. This study delves into the impact of zinc and lead pollution on the particle size distribution, liquid-plastic limit, permeability, shear strength, and other pertinent physical and engineering properties of clay. The alterations in the microstructure of soil contaminated by heavy metals were scrutinized using a scanning electron microscope. The findings reveal that as the concentration of heavy metals in contaminated soil rises, there is a concurrent decrease in the liquid limit, plasticity index, and silt content. This, in turn, leads to the deterioration of the original fluidity and plasticity of the soil, accompanied by a reduction in fine particles. Resistivity tests indicate that an escalation in water content results in a decrease in resistivity, an increase in porosity leads to an increase in resistivity, and an elevation in the concentration of heavy metals precipitates a sharp decline in resistivity due to the heightened conductivity of heavy metal ions. Heavy metal pollution induces structural changes in the soil, particularly in pore size, thereby influencing the permeability coefficient.

Ecological stoichiometry (ES) is an important index that reflects the balance of various elements in ecological processes. Therefore, it is of great significance to understand the soil nutrient cycle to clarify the environmental control of soil carbon (C), nitrogen (N), phosphorus (P), and potassium (K). In this study, we analyzed the spatial distribution of soil C, N, P, and K contents and the C:N:P:K stoichiometric characteristics of 0–20 cm and 20–40 cm of farmland and grassland in four agro-pastoral areas in Inner Mongolia. Spearman correlation was used to analyze the effects of environmental factors on the soil C:N:P:K stoichiometric relationship. The results showed that there was no fixed Redfield ratio for the soil stoichiometric relationship of farmland and grassland in Inner Mongolia, and the values were 15:2:1:9 to 145:10:1:26 and 25:1:1:29 to 228:15:1:65, respectively. The stoichiometric relationships between farmland and grassland were consistent with the law of geographical and spatial heterogeneity. The ratios of C:N, C:P, C:K, N:P, and N:K showed an N distribution from west to east, while the ratio of P:K showed a V distribution. The stoichiometric relationships in grassland soil were mainly affected by soil organic carbon and total nitrogen content, while those in farmland were mainly affected by total nitrogen and total phosphorus content. The annual mean precipitation has a significant effect on stoichiometric relationships in farmland, while the annual mean temperature has a more significant effect on grassland. In conclusion, the spatial distribution difference in the soil stoichiometric relationship in the agro-pastoral ecotone of Inner Mongolia was more significant than the difference in the land use pattern. The influences of annual mean temperature and annual mean precipitation on soil ecological stoichiometry were in accordance with the geographical spatial similarity law. Compared with grassland, the stoichiometric relationship of farmland soil was greatly affected by fertilization, and farmland in this region was mainly limited by carbon and nitrogen. Thus, field management should be carried out according to local conditions. This study is of great significance as it promotes the rational utilization of land resources and the sustainable development of agriculture.

Objective·To analyze the effects of maternal high-fat diet on placental phenotype, and investigate the role of placental microenvironment in the intergenerational transmission.Methods·The 3-week-old C57BL/6J female mice were fed with either the high-fat diet (HFD group) or the control diet (CD group) for 5 weeks before mating and throughout gestation. Placentas and fetal liver tissues were collected from maternal mice after 20 d of gestation. The effects of maternal HFD on the placental inflammation and placental structure were investigated by hematoxylin-eosin staining (H-E staining), immunohistochemistry, Western blotting and RT-PCR. The lipid deposition levels in fetal livers were also detected. Body weight changes, fasting blood glucose and glucose tolerance levels of the 3-week-old weaned mice were also detected.Results·The body weight of female mice in the HFD group increased significantly, and the liver triacylglycerol (TAG) and total cholesterol (TC) levels were higher than those in the CD group (all P0.05). Compared to the CD group, the body weight, fasting blood glucose level and the area under the glucose tolerance curve of the 3-week-old weaned mice of the HFD group were increased significantly (all P

Abstract Background Cholesterol plays a vital role in multiple physiological processes. Cellular uptake of cholesterol is mediated primarily through endocytosis of low-density lipoprotein (LDL) receptor. New modifiers of this process remain to be characterized. Particularly, the role of fasting- and CREB-H-induced (FACI) protein in cholesterol homeostasis merits further investigation. Methods Interactome profiling by proximity labeling and affinity purification − mass spectrometry was performed. Total internal reflection fluorescence microscopy and confocal immunofluorescence microscopy were used to analyze protein co-localization and interaction. Mutational analysis was carried out to define the domain and residues required for FACI localization and function. Endocytosis was traced by fluorescent cargos. LDL uptake in cultured cells and diet-induced hypercholesterolemia in mice were assessed. Results FACI interacted with proteins critically involved in clathrin-mediated endocytosis, vesicle trafficking, and membrane cytoskeleton. FACI localized to clathrin-coated pits (CCP) on plasma membranes. FACI contains a conserved DxxxLI motif, which mediates its binding with the adaptor protein 2 (AP2) complex. Disruption of this motif of FACI abolished its CCP localization but didn’t affect its association with plasma membrane. Cholesterol was found to facilitate FACI transport from plasma membrane to endocytic recycling compartment in a clathrin- and cytoskeleton-dependent manner. LDL endocytosis was enhanced in FACI-overexpressed AML12 cells but impaired in FACI-depleted HeLa cells. In vivo study indicated that hepatic FACI overexpression alleviated diet-induced hypercholesterolemia in mice. Conclusions FACI facilitates LDL endocytosis through its interaction with the AP2 complex.

The observation data procession of target about traditional naval gun is based on installation site,dues to factors such as swing and deformation datum change will cause observation data error and affect firing accuracy,this paper analyzes the naval gun firing accutacy caused by the state of platform and naval gun enchmark assumptions, new methods of data processing is put forward, the mathematical model for calculating the arameters of observation target is established, which provides a new way to process the observation data.

The author of this article concerns with the existence, uniqueness, and stability of the weak solution to the variation-inequality problem. The Kirchhoff operator is a non-divergence form with space variable parameter. The existence of generalized solution is proved by the Leray-Schauder principle and parabolic regularization. The uniqueness and stability of the solution are also discussed by contradiction.

Objective To find an intelligent method to quantify perioperative trauma stress, digitize and visualize perioperative patients stress status and recovery process, and analyze the mechanism of enhanced recovery after surgery (ERAS) strategy to promote rapid recovery of patients from the perspective of autonomic nervous system (ANS). Methods The clinical data of 125 patients received laparoscopic radical resection of colorectal cancer in Jiangsu Province Hospital of Chinese Medicine from February 2020 to May 2022 were retrospectively analyzed. According to the treatment methods, they were divided into ERAS group and control group. A total of 66 patients were included in this study after propensity score matching (PSM) was used to equalize covariates between groups, with 33 patients in each group. The hospital stay, high-sensitivity C-reactive protein (hs-CRP), HRV parameters (SDNN, pNN50, LF/HF) and the variation of heart rate curve were compared between two groups. Results There was no significant difference in hs-CRP and HRV parameters between the two groups on admission day (P>0.05). The hospital stay and postoperative hs-CRP in ERAS group were lower than those in control group (P0.05). The difference between 4th day after operation and admission was significant at parameters of HRV in control group (P

With the rapid development of civil aviation industry, more and more tasks are required to fuel the aircraft. At present, the aircraft refueling task is mainly assigned to the refueling personnel by the dispatcher of the fuel supplier, one by one, according to the flight refueling information, after receiving the task, the refueling operator drives the refueling vehicle to the aircraft for refueling operation. The realization of electronic, information and big data analysis technology has gradually opened up the information channel of refueling system. Based on a large number of multi-dimensional data, according to the characteristics of aircraft refueling operation, an intelligent dispatching method for aircraft refueling vehicle is provided, which can automatically assign refueling tasks, avoid flight delays and the resulting serious waste of resources and can reduce the workload of the dispatcher. Through the intelligent dispatch, refueling resources can be reasonably allocated to ensure the timely refueling of aircraft and smooth completion of flight support tasks.