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Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in the biosynthesis of taurine from cysteine and in the downstream metabolism of secondary taurine metabolites4,5. One taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise7, dietary taurine supplementation8 and alcohol consumption6,9. So far, the identities of the enzymes involved in N-acetyltaurine metabolism, and the potential functions of N-acetyltaurine itself, have remained unknown. Here we show that the body mass index associated orphan enzyme phosphotriesterase-related (PTER)10 is a physiological N-acetyltaurine hydrolase. In vitro, PTER catalyses the hydrolysis of N-acetyltaurine to taurine and acetate. In mice, PTER is expressed in the kidney, liver and brainstem. Genetic ablation of Pter in mice results in complete loss of tissue N-acetyltaurine hydrolysis activity and a systemic increase in N-acetyltaurine levels. After stimuli that increase taurine levels, Pter knockout mice exhibit reduced food intake, resistance to diet-induced obesity and improved glucose homeostasis. Administration of N-acetyltaurine to obese wild-type mice also reduces food intake and body weight in a GFRAL-dependent manner. These data place PTER into a central enzymatic node of secondary taurine metabolism and uncover a role for PTER and N-acetyltaurine in body weight control and energy balance.

Great progress has been made in understanding gut microbiomes products and their effects on health and disease. Less attention, however, has been given to the inputs that gut bacteria consume. Here, we quantitatively examine inputs and outputs of the mouse gut microbiome, using isotope tracing. The main input to microbial carbohydrate fermentation is dietary fiber and to branched-chain fatty acids and aromatic metabolites is dietary protein. In addition, circulating host lactate, 3-hydroxybutyrate, and urea (but not glucose or amino acids) feed the gut microbiome. To determine the nutrient preferences across bacteria, we traced into genus-specific bacterial protein sequences. We found systematic differences in nutrient use: most genera in the phylum Firmicutes prefer dietary protein, Bacteroides dietary fiber, and Akkermansia circulating host lactate. Such preferences correlate with microbiome composition changes in response to dietary modifications. Thus, diet shapes the microbiome by promoting the growth of bacteria that preferentially use the ingested nutrients.

Homeostasis maintains serum metabolites within physiological ranges. For glucose, this requires insulin, which suppresses glucose production while accelerating its consumption. For other circulating metabolites, a comparable master regulator has yet to be discovered. Here we show that, in mice, many circulating metabolites are cleared via the tricarboxylic acid cycle (TCA) cycle in linear proportionality to their circulating concentration. Abundant circulating metabolites (essential amino acids, serine, alanine, citrate, 3-hydroxybutyrate) were administered intravenously in perturbative amounts and their fluxes were measured using isotope labelling. The increased circulating concentrations induced by the perturbative infusions hardly altered production fluxes while linearly enhancing consumption fluxes and TCA contributions. The same mass action relationship between concentration and consumption flux largely held across feeding, fasting and high- and low-protein diets, with amino acid homeostasis during fasting further supported by enhanced endogenous protein catabolism. Thus, despite the copious regulatory machinery in mammals, circulating metabolite homeostasis is achieved substantially through mass action-driven oxidation.

Mammalian organs are nourished by nutrients carried by the blood circulation. These nutrients originate from diet and internal stores, and can undergo various interconversions before their eventual use as tissue fuel. Here we develop isotope tracing, mass spectrometry, and mathematical analysis methods to determine the direct sources of circulating nutrients, their interconversion rates, and eventual tissue-specific contributions to TCA cycle metabolism. Experiments with fifteen nutrient tracers enabled extensive accounting for both circulatory metabolic cycles and tissue TCA inputs, across fed and fasted mice on either high-carbohydrate or ketogenic diet. We find that a majority of circulating carbon flux is carried by two major cycles: glucose-lactate and triglyceride-glycerol-fatty acid. Futile cycling through these pathways is prominent when dietary content of the associated nutrients is low, rendering internal metabolic activity robust to food choice. The presented in vivo flux quantification methods are broadly applicable to different physiological and disease states.

Per capita fructose consumption has increased 100-fold over the last century1. Epidemiological studies suggest that excessive fructose consumption, and especially consumption of sweet drinks, is associated with hyperlipidaemia, non-alcoholic fatty liver disease, obesity and diabetes2-7. Fructose metabolism begins with its phosphorylation by the enzyme ketohexokinase (KHK), which exists in two alternatively spliced forms8. The more active isozyme, KHK-C, is expressed most strongly in the liver, but also substantially in the small intestine9,10 where it drives dietary fructose absorption and conversion into other metabolites before fructose reaches the liver11-13. It is unclear whether intestinal fructose metabolism prevents or contributes to fructose-induced lipogenesis and liver pathology. Here we show that intestinal fructose catabolism mitigates fructose-induced hepatic lipogenesis. In mice, intestine-specific KHK-C deletion increases dietary fructose transit to the liver and gut microbiota and sensitizes mice to fructose's hyperlipidaemic effects and hepatic steatosis. In contrast, intestine-specific KHK-C overexpression promotes intestinal fructose clearance and decreases fructose-induced lipogenesis. Thus, intestinal fructose clearance capacity controls the rate at which fructose can be safely ingested. Consistent with this, we show that the same amount of fructose is more strongly lipogenic when drunk than eaten, or when administered as a single gavage, as opposed to multiple doses spread over 45 min. Collectively, these data demonstrate that fructose induces lipogenesis when its dietary intake rate exceeds the intestinal clearance capacity. In the modern context of ready food availability, the resulting fructose spillover drives metabolic syndrome. Slower fructose intake, tailored to intestinal capacity, can mitigate these consequences.

Consumption of fructose has risen markedly in recent decades owing to the use of sucrose and high-fructose corn syrup in beverages and processed foods1, and this has contributed to increasing rates of obesity and non-alcoholic fatty liver disease2-4. Fructose intake triggers de novo lipogenesis in the liver4-6, in which carbon precursors of acetyl-CoA are converted into fatty acids. The ATP citrate lyase (ACLY) enzyme cleaves cytosolic citrate to generate acetyl-CoA, and is upregulated after consumption of carbohydrates7. Clinical trials are currently pursuing the inhibition of ACLY as a treatment for metabolic diseases8. However, the route from dietary fructose to hepatic acetyl-CoA and lipids remains unknown. Here, using in vivo isotope tracing, we show that liver-specific deletion of Acly in mice is unable to suppress fructose-induced lipogenesis. Dietary fructose is converted to acetate by the gut microbiota9, and this supplies lipogenic acetyl-CoA independently of ACLY10. Depletion of the microbiota or silencing of hepatic ACSS2, which generates acetyl-CoA from acetate, potently suppresses the conversion of bolus fructose into hepatic acetyl-CoA and fatty acids. When fructose is consumed more gradually to facilitate its absorption in the small intestine, both citrate cleavage in hepatocytes and microorganism-derived acetate contribute to lipogenesis. By contrast, the lipogenic transcriptional program is activated in response to fructose in a manner that is independent of acetyl-CoA metabolism. These data reveal a two-pronged mechanism that regulates hepatic lipogenesis, in which fructolysis within hepatocytes provides a signal to promote the expression of lipogenic genes, and the generation of microbial acetate feeds lipogenic pools of acetyl-CoA.

Mammalian organs continually exchange metabolites via circulation, but systems-level analysis of this shuttling process is lacking. Here, we compared, in fasted pigs, metabolite concentrations in arterial blood versus draining venous blood from 11 organs. Greater than 90% of metabolites showed arterial-venous differences across at least one organ. Surprisingly, the liver and kidneys released not only glucose but also amino acids, both of which were consumed primarily by the intestine and pancreas. The liver and kidneys exhibited additional unexpected activities: liver preferentially burned unsaturated over more atherogenic saturated fatty acids, whereas the kidneys were unique in burning circulating citrate and net oxidizing lactate to pyruvate, thereby contributing to circulating redox homeostasis. Furthermore, we observed more than 700 other cases of tissue-specific metabolite production or consumption, such as release of nucleotides by the spleen and TCA intermediates by pancreas. These data constitute a high-value resource, providing a quantitative atlas of inter-organ metabolite exchange.

This paper presents an adaptive sliding mode control (ASMC) scheme based on strain gauge position feedback for compensating for motion errors in a piezoelectric nanopositioning stages and ensures precise and reliable motion tracking control. The innovation of this scheme lies in calibrating the relationship between the feedback voltage of the strain gauge and the actual stage displacement. Thus, the calibrated feedback displacement is directly used as the position feedback signal for the ASMC scheme. Adaptive rules are employed to adjust the control gains, thereby eliminating the requirement to determine the upper bound of the disturbance. The stability of the ASMC strategy is theoretically proven within the Lyapunov framework. Comparative experiments under external disturbances have confirmed the superiority of the proposed control scheme. Results demonstrate that the proposed control scheme exhibits superior robust tracking performance compared to the traditional sliding mode control (SMC) scheme. [ABSTRACT FROM AUTHOR]

This paper presents the design of a sliding mode controller to compensate hysteresis nonlinearity and achieve precision motion tracking for a novel piezoelectric tip/tilt platform driven by a PZT actuator. The sliding mode control scheme is based on the unique physical characteristics of the piezoelectric tip/tilt platform. The proposed scheme effectively guides the platform state onto a predefined sliding surface and ensures its sustained movement along this manifold. This approach reduces tracking errors compared to conventional methodologies. The stability of the sliding mode control scheme is demonstrated by the Lyapunov theory framework. It achieves precise motion control with minimal tracking error on a piezoelectric tip/tilt platform. The properties of the controller have been confirmed through experimental tests. The proposed control scheme enhances the robust tracking and stability performance on the piezoelectric tip/tilt platform, outperforming traditional control schemes. Compared with the P562.6CD produced by PI Germany, the proposed innovative approach not only boosts the platform's resolution by 32% but also implements a 33% reduction in cost. [ABSTRACT FROM AUTHOR]

With the development of artificial intelligence technology, it has become convenient for people to work, study and travel and face recognition is widely used in many fields, but also brings a lot of hidden dangers to security. Aiming at the problem of reduced accuracy of face detection algorithm caused by local occlusion factors, The paper proposes a partial occlusion face recognition method based on DCGAN face repair combined with ResNet. The experimental results show that the algorithm proposed in the paper has better face recognition effect when there is partial occlusion in the face. [ABSTRACT FROM AUTHOR]

Objective To observe the efficacy of ivabradine combined with levosimendan in patients with acute myocardial infarction complicated with heart failure. Methods A total of 78 patients with acute myocardial infarction complicated with heart failure admitted to the hospital from May 1, 2020 to December 31, 2022 were selected and divided into control group (n = 39) and study group (n = 39) by random number table method. In addition to basic treatment, the control group received levosimendan, and the study group ivabradine and levosimendan. The treatment period of both groups was 4 weeks. Compare two groups of patients' vital signs, clinical curative effect and heart function index, serological indexes, inflammatory factors and security. Results Compared with before treatment, the systolic blood pressure, diastolic blood pressure and heart rate of the two groups were decreased after treatment (P < 0.05), and the systolic blood pressure, heart rate, diastolic blood pressure and heart rate of the study group were significantly decreased compared with the control group (P < 0.05). Compared with the control group, the total effective rate of the study group was significantly higher (P < 0.05). Compared with before treatment, the levels of CO and LVEF were increased (P < 0.05), while the levels of LVEDV and LVESV were decreased (P < 0.05). Compared with the control group, the levels of CO and LVEF in the study group were higher (P < 0.05), and the levels of LVEDV and LVESV in the study group were lower (P < 0.05). Compared with before treatment, the levels of cTnI, sST2 and NT-proBNP in both groups were decreased after treatment (P < 0.05), and the serum levels of cTnI, sST2 and NT-proBNP in the study group were significantly decreased compared with the control group (P < 0.05). Tumor necrosis factor α (TNF-α), myeloperoxidase (MPO) and highly sensitive C-reactive protein (hs-CRP) were all decreased after treatment in the two groups (P < 0.05), and those in the study group were much lower (P < 0.05 ) No difference between the incidence of adverse reactions to the total contrast the two groups (P > 0.05). Conclusion Levosimendan combined with ivabadinehave a definite effect on patients with acute myocardial infarction complicated with heart failure for the improved cardiac function, reduced inflammation, regulated serum sST2, cTnI, and NT-proBNP level. It is also safe and reliable [ABSTRACT FROM AUTHOR]

This study conducts a detailed 23-year analysis of Density Altitude (DA) at 34 major airports across China, utilizing Meteorological Aviation Routine Weather Report (METAR) datasets, and discovers significant regional DA variations due to the country's diverse topography and climate. Central and eastern regions exhibit higher DA values because of lower atmospheric pressures at higher altitudes, while northeastern airports have lower DA values, attributed to colder temperatures and lower elevations. A crucial finding is the substantial impact of humidity on DA, particularly in the southern coastal regions, a factor often neglected in pilot training, highlighting the necessity to revise aviation education to include humidity's impact on DA. The study advocates for a region-specific approach to Chinese aviation operations, tailored to local DA influences, and suggests strategic adjustments in flight planning and risk assessment to address these regional differences, enhancing aviation safety and efficiency. [ABSTRACT FROM AUTHOR]