real-time-sampling-rat-femoral-arteriovenous-adventitial-interstitial

Real-Time Sampling of Rat Femoral Arteriovenous Adventitial Interstitial Fluid by Placement of a Microdialysis Probe

Interstitial fluid (ISF) is a vital element of the extracellular microenvironment, facilitating metabolic exchange and intercellular communication. ...

Chinese Academy of Medical Sciences

China Academy Of Chinese Medical Sciences

Less is known about the risk factors for acute respiratory distress syndrome (ARDS) in sepsis patients diagnosed according to sepsis 3.0 criteria. Moreover, the risk factors for ARDS severity remain unclear.

Risk factors for acute respiratory distress syndrome in sepsis patients: a retrospective study from a tertiary hospital in China.

Human mutations in the gene encoding the solute carrier (SLC) 6A17 caused intellectual disability (ID). The physiological role of  and pathogenesis of -based-ID were both unclear. Here, we report learning deficits in  knockout and point mutant mice. Biochemistry, proteomic, and electron microscopy (EM) support SLC6A17 protein localization in synaptic vesicles (SVs). Chemical analysis of SVs by liquid chromatography coupled to mass spectrometry (LC-MS) revealed glutamine (Gln) in SVs containing SLC6A17. Virally mediated overexpression of SLC6A17 increased Gln in SVs. Either genetic or virally mediated targeting of  reduced Gln in SVs. One ID mutation caused SLC6A17 mislocalization while the other caused defective Gln transport. Multidisciplinary approaches with seven types of genetically modified mice have shown Gln as an endogenous substrate of SLC6A17, uncovered Gln as a new molecule in SVs, established the necessary and sufficient roles of SLC6A17 in Gln transport into SVs, and suggested SV Gln decrease as the key pathogenetic mechanism in human ID.

Importance of glutamine in synaptic vesicles revealed by functional studies of  and its mutations pathogenic for intellectual disability.

The discovery of a new neurotransmitter, especially one in the central nervous system, is both important and difficult. We have been searching for new neurotransmitters for 12 y. We detected creatine (Cr) in synaptic vesicles (SVs) at a level lower than glutamate and gamma-aminobutyric acid but higher than acetylcholine and 5-hydroxytryptamine. SV Cr was reduced in mice lacking either arginine:glycine amidinotransferase (a Cr synthetase) or SLC6A8, a Cr transporter with mutations among the most common causes of intellectual disability in men. Calcium-dependent release of Cr was detected after stimulation in brain slices. Cr release was reduced in  and  mutants. Cr inhibited neocortical pyramidal neurons. SLC6A8 was necessary for Cr uptake into synaptosomes. Cr was found by us to be taken up into SVs in an ATP-dependent manner. Our biochemical, chemical, genetic, and electrophysiological results are consistent with the possibility of Cr as a neurotransmitter, though not yet reaching the level of proof for the now classic transmitters. Our novel approach to discover neurotransmitters is to begin with analysis of contents in SVs before defining their function and physiology.

Suggestion of creatine as a new neurotransmitter by approaches ranging from chemical analysis and biochemistry to electrophysiology.

Hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is a major contributor to mortality. We developed a recurrence prediction system for HCC patients before and after LT. Data from patients with HCC who underwent LT were retrospectively collected from three specialist centres in China. Pre- and post-operative variables were selected using support vector machine, random forest, and logistic regression (LR). Then, pre- and post-operative models were developed using three machine learning methods: LR, stacking, and two survival-based approaches. Models were evaluated using seven assessment indices, and patients were classified as either high- or low-risk based on recurrence risk. 466 patients were included and followed for a median of 51.0 months (95% CI 47.8-54.2). The pre-DeepSurv model (pre-DSM) had a C-index of 0.790 ± 0.003 during training, 0.775 ± 0.037 during testing, and 0.765 ± 0.001 and 0.819 ± 0.002 during external validation. After incorporating clinicopathologic variables, the post-DeepSurv model (post-DSM) had a 0.835 ± 0.008 C-index during training, 0.812 ± 0.082 during testing, and 0.839 ± 0.001 and 0.831 ± 0.002 during external validation. The post-DSM outperformed the Milan criteria by more accurately identifying patients at high risk of recurrence. Tumour recurrence predictions also improved significantly with DeepSurv. Both pre- and post-DSMs have the potential to guide personalised surveillance strategies for LT patients with HCC.

Article	Year
Risk factors for acute respiratory distress syndrome in sepsis patients: a retrospective study from a tertiary hospital in China. BMC pulmonary medicine\| PubMed ID: 35729588	2022
Importance of glutamine in synaptic vesicles revealed by functional studies of and its mutations pathogenic for intellectual disability. eLife\| PubMed ID: 37440432	2023
Suggestion of creatine as a new neurotransmitter by approaches ranging from chemical analysis and biochemistry to electrophysiology. eLife\| PubMed ID: 38126335	2023
Deep learning for hepatocellular carcinoma recurrence before and after liver transplantation: a multicenter cohort study. Scientific reports\| PubMed ID: 40044774	2025

SiHan Yu

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