Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease: current knowledge and new insights.

Phenylacetylglutamine (PAGln) is an amino acid derivate that comes from the amino acid phenylalanine. There are increasing studies showing that the level of PAGln is associated with the risk of different cardiovascular diseases. In this review, we discussed the metabolic pathway of PAGln production and the quantitative measurement methods of PAGln. We summarized the epidemiological evidence to show the role of PAGln in diagnostic and prognostic value in several cardiovascular diseases, such as heart failure, coronary heart disease/atherosclerosis, and cardiac arrhythmia. The underlying mechanism of PAGln is now considered to be related to the thrombotic potential of platelets via adrenergic receptors. Besides, other possible mechanisms such as inflammatory response and oxidative stress could also be induced by PAGln. Moreover, since PAGln is produced across different organs including the intestine, liver, and kidney, the cross-talk among multiple organs focused on the function of this uremic toxic metabolite. Finally, the prognostic value of PAGln compared to the classical biomarker was discussed and we also highlighted important gaps in knowledge and areas requiring future investigation of PAGln in cardiovascular diseases.

Increased circulating phenylacetylglutamine concentration elevates the predictive value of cardiovascular event risk in heart failure patients.

BACKGROUND: Phenylacetylglutamine (PAGln)-a newly discovered microbial metabolite produced by phenylalanine metabolism-is reportedly associated with cardiovascular events via adrenergic receptors. Nonetheless, its association with cardiovascular outcomes in heart failure (HF) patients remains unknown. OBJECTIVES: This study aimed to prospectively investigate the prognostic value of PAGln for HF. METHODS: Plasma PAGln levels were quantified by liquid chromatography-tandem mass spectrometry. We first assessed the association between plasma PAGln levels and the incidence of adverse cardiovascular events in 3152 HF patients (including HF with preserved and reduced ejection fraction) over a median follow-up period of 2 years. The primary endpoint was the composite of cardiovascular death or heart transplantation. We then assessed the prognostic role of PAGln in addition to the classic biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP). The correlation between PAGln levels and ß-blocker use was also investigated. RESULTS: In total, 520 cardiovascular deaths or heart transplantations occurred in the HF cohort. Elevated PAGln levels were independently associated with a higher risk of the primary endpoint in a dose-response manner, regardless of HF subtype. Concurrent assessment of PAGln and NT-proBNP levels enhanced risk stratification among HF patients. PAGln further showed prognostic value at low NT-proBNP levels. Additionally, the interaction effects between PAGln and ß-blocker use were not significant. CONCLUSIONS: Plasma PAGln levels are an independent predictor of an increased risk of adverse cardiovascular events in HF. Our work could provide joint and complementary prognostic value to NT-proBNP levels in HF patients.

Realization of an ultra-high precision temperature control in a cryogen-free cryostat.

Single-pressure refractive-index gas thermometry (SPRIGT) is a new type primary thermometry jointly developed by TIPC of CAS in China and LNE-Cnam in France. To realize a competitive uncertainty of 0.25 mK for the thermodynamic temperature measurement, a cryogen-free cryostat with high-stability better than 0.2 mK should be designed. This paper presented the first experimental results of temperature control for this cryostat. To realize this objective, multi-layer radiation shields combined with a thermal-resistance method were used to isolate the thermal-noise from surroundings. Besides, a new temperature control method based on a gas-type heat switch and proportional-integral-derivative control method was proposed, which was applicable to different temperature ranges by changing the working modes of the heat switch. After optimizing, the ultra-high precision temperature control in the range of 5-25 K has been fully realized, which was the temperature instability (with standard deviation) of 0.021 mK at 5.0 K, 0.05 mK at 5.7 K, 0.042 mK at 7.4 K, 0.029 mK at 14.3 K, and 0.022 mK at 25 K with the sampling time of 0.8 s. This was almost the best reporting result in the world and showed its great potential in SPRIGT.