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Background: Arterial remodeling is a common pathophysiological change in the pathogenesis of cardiovascular diseases in which the phenotypic switch of vascular smooth muscle cells (VSMC) plays an important role. Recently, an increasing number of long non-coding RNAs(lncRNAs) have been shown to encode micropeptides that play biological roles and have great clinical transformation potential. However, the role of micropeptides encoded by lncRNAs in arterial remodeling has not been well studied and requires further exploration., Methods and Results: Through bioinformatic analysis and experimental verification, we found that a new lncRNA, the mitochondrial function-related lncRNA (MFRL), encodes a 64-amino acid micropeptide, MFRLP. MFRL and MFRLP play important roles in the phenotypic switch of VSMC. Further experiments showed that MFRLP interacts with mitochondrial cytochrome b to reduce accumulation of reactive oxygen species, suppress mitophagy and inhibit the VSMC switch from contractile to synthetic phenotype., Conclusions: LncRNA MFRL encodes the micropeptide MFRLP, which interacts with mitochondrial cytochrome b to inhibit the VSMC switch from contractile to synthetic phenotype and improve arterial remodeling., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Benefiting from rich knowledge and the exceptional ability to understand text, large language models like ChatGPT have shown great potential in English clinical environments. However, the performance of ChatGPT in non-English clinical settings, as well as its reasoning, have not been explored in depth., Objective: This study aimed to evaluate ChatGPT's diagnostic performance and inference abilities for retinal vascular diseases in a non-English clinical environment., Methods: In this cross-sectional study, we collected 1226 fundus fluorescein angiography reports and corresponding diagnoses written in Chinese and tested ChatGPT with 4 prompting strategies (direct diagnosis or diagnosis with a step-by-step reasoning process and in Chinese or English)., Results: Compared with ChatGPT using Chinese prompts for direct diagnosis that achieved an F 1 -score of 70.47%, ChatGPT using English prompts for direct diagnosis achieved the best diagnostic performance (80.05%), which was inferior to ophthalmologists (89.35%) but close to ophthalmologist interns (82.69%). As for its inference abilities, although ChatGPT can derive a reasoning process with a low error rate (0.4 per report) for both Chinese and English prompts, ophthalmologists identified that the latter brought more reasoning steps with less incompleteness (44.31%), misinformation (1.96%), and hallucinations (0.59%) (all P<.001). Also, analysis of the robustness of ChatGPT with different language prompts indicated significant differences in the recall (P=.03) and F 1 -score (P=.04) between Chinese and English prompts. In short, when prompted in English, ChatGPT exhibited enhanced diagnostic and inference capabilities for retinal vascular disease classification based on Chinese fundus fluorescein angiography reports., Conclusions: ChatGPT can serve as a helpful medical assistant to provide diagnosis in non-English clinical environments, but there are still performance gaps, language disparities, and errors compared to professionals, which demonstrate the potential limitations and the need to continually explore more robust large language models in ophthalmology practice., (©Xiaocong Liu, Jiageng Wu, An Shao, Wenyue Shen, Panpan Ye, Yao Wang, Juan Ye, Kai Jin, Jie Yang. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.01.2024.)

Sepsis is a leading cause of fatality in invasive candidiasis. The magnitude of the inflammatory response is a determinant of sepsis outcomes, and inflammatory cytokine imbalances are central to the pathophysiological processes. We previously demonstrated that a Candida albicans F 1 F o -ATP synthase α subunit deletion mutant was nonlethal to mice. Here, the potential effects of the F 1 F o -ATP synthase α subunit on host inflammatory responses and the mechanism were studied. Compared with wild-type strain, the F 1 F o -ATP synthase α subunit deletion mutant failed to induce inflammatory responses in Galleria mellonella and murine systemic candidiasis models and significantly decreased the mRNA levels of the proinflammatory cytokines IL-1β, IL-6 and increased those of the anti-inflammatory cytokine IL-4 in the kidney. During C. albicans -macrophage co-culture, the F 1 F o -ATP synthase α subunit deletion mutant was trapped inside macrophages in yeast form, and its filamentation, a key factor in inducing inflammatory responses, was inhibited. In the macrophage-mimicking microenvironment, the F 1 F o -ATP synthase α subunit deletion mutant blocked the cAMP/PKA pathway, the core filamentation-regulating pathway, because it failed to alkalinize environment by catabolizing amino acids, an important alternative carbon source inside macrophages. The mutant downregulated Put1 and Put2, two essential amino acid catabolic enzymes, possibly due to severely impaired oxidative phosphorylation. Our findings reveal that the C. albicans F 1 F o -ATP synthase α subunit induces host inflammatory responses by controlling its own amino acid catabolism and it is significant to find drugs that inhibit F 1 F o -ATP synthase α subunit activity to control the induction of host inflammatory responses.

Objective: To investigate the prognostic value of early serum lactate, albumin, and lactate/albumin ratio (L/A) on the 28-day prognosis of adult patients with sepsis., Methods: A retrospective cohort study was conducted among adult patients with sepsis admitted to the First Affiliated Hospital of Xinjiang Medical University from January to December in 2020. Gender, age, comorbidities, lactate within 24 hours of admission, albumin, L/A, interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and 28-day prognosis were recorded. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of lactate, albumin and L/A for 28-day mortality in patients with sepsis. Subgroup analysis of patients was performed according to the best cut-off value, Kaplan-Meier survival curves were drawn, and the 28-day cumulative survival of patients with sepsis was analyzed., Results: A total of 274 patients with sepsis were included, and 122 patients died at 28 days, with a 28-day mortality of 44.53%. Compared with the survival group, the age, the proportion of pulmonary infection, the proportion of shock, lactate, L/A and IL-6 in the death group were significantly increased, and albumin was significantly decreased [age (years): 65 (51, 79) vs. 57 (48, 73), pulmonary infection: 75.4% vs. 53.3%, shock: 37.7% vs. 15.1%, lactate (mmol/L): 4.76 (2.95, 9.23) vs. 2.21 (1.44, 3.19), L/A: 0.18 (0.10, 0.35) vs. 0.08 (0.05, 0.11), IL-6 (ng/L): 337.00 (97.73, 2 318.50) vs. 55.88 (25.26, 150.65), albumin (g/L): 27.68 (21.02, 33.03) vs. 29.62 (25.25, 34.23), all P < 0.05]. The area under the ROC curve (AUC) and 95% confidence interval (95%CI) of lactate, albumin, and L/A were 0.794 (95%CI was 0.741-0.840), 0.589 (95%CI was 0.528-0.647), 0.807 (95%CI was 0.755-0.852) for predicting 28-day mortality in sepsis patients. The optimal diagnostic cut-off value of lactate was 4.07 mmol/L, the sensitivity was 57.38%, the specificity was 92.76%. The optimal diagnostic cut-off value of albumin was 22.28 g/L, the sensitivity was 31.15%, the specificity was 92.76%. The optimal diagnostic cut-off of L/A was 0.16, the sensitivity was 54.92%, and the specificity was 95.39%. Subgroup analysis showed that the 28-day mortality of sepsis patients in the L/A > 0.16 group was significantly higher than that in the L/A ≤ 0.16 group [90.5% (67/74) vs. 27.5% (55/200), P < 0.001]. The 28-day mortality of sepsis patients in the albumin ≤ 22.28 g/L group was significantly higher than that in the albumin > 22.28 g/L group [77.6% (38/49) vs. 37.3% (84/225), P < 0.001]. The 28-day mortality in the group with lactate > 4.07 mmol/L was significantly higher than that in the group with lactate ≤ 4.07 mmol/L [86.4% (70/81) vs. 26.9% (52/193), P < 0.001]. The three were consistent with the analysis results of Kaplan-Meier survival curve., Conclusions: The early serum lactate, albumin, and L/A were all valuable in predicting the 28-day prognosis of patients with sepsis, and L/A was better than lactate and albumin.

Defects in mitochondria are responsible for various genetic and acquired diseases. Mitochondrial transplantation, a method that involves introduction of healthy donor mitochondria into cells with dysfunctional mitochondria, could offer a novel approach to treat such diseases. Some studies have demonstrated the therapeutic benefit of mitochondrial transplantation and targeted delivery in vivo and in vitro within hepatocytes and the liver. This review discusses the issues regarding isolation and delivery of mitochondria to hepatocytes and the liver, and examines the existing literature in order to elucidate the utility and practicality of mitochondrial transplantation in the treatment of liver disease. Studies reviewed demonstrate that mitochondrial uptake could specifically target hepatocytes, address the challenge of non-specific localization of donor mitochondria, and provide evidence of changes in liver function following injection of mitochondria into mouse and rat disease models. While potential benefits and advantages of mitochondrial transplantation are evident, more research is needed to determine the practicality of mitochondrial transplantation for the treatment of genetic and acquired liver diseases., Competing Interests: GYW has been the editor-in-chief of Journal of Clinical and Translational Hepatology since 2012. The other authors have no conflict of interests related to this publication., (© 2022 Authors.)

The development, persistence and relapse of drug addiction require drug memory that generally develops with drug administration-paired contextual stimuli. Adult hippocampal neurogenesis (AHN) contributes to cocaine memory formation; however, the underlying mechanism remains unclear. Male mice hippocampal expression of Tau was significantly decreased during the cocaine-associated memory formation. Genetic overexpression of four microtubule-binding repeats Tau (4R Tau) in the mice hippocampus disrupted cocaine memory by suppressing AHN. Furthermore, 4R Tau directly interacted with phosphoinositide 3-kinase (PI3K)-p85 and impaired its nuclear translocation and PI3K-AKT signaling, processes required for hippocampal neuron proliferation. Collectively, 4R Tau modulates cocaine memory formation by disrupting AHN, suggesting a novel mechanism underlying cocaine memory formation and provide a new strategy for the treatment of cocaine addiction. SIGNIFICANCE STATEMENT Drug memory that generally develops with drug-paired contextual stimuli and drug administration is critical for the development, persistence and relapse of drug addiction. Previous studies have suggested that adult hippocampal neurogenesis (AHN) plays a role in cocaine memory formation. Here, we showed that Tau was significantly downregulated in the hippocampus in the cocaine memory formation. Tau knock-out (KO) promoted AHN in the hippocampal dentate gyrus (DG), resulting in the enhanced memory formation evoked by cocaine-cue stimuli. In contrast, genetically overexpressed 4R Tau in the hippocampus disrupted cocaine-cue memory by suppressing AHN. In addition, 4R Tau interacted directly with phosphoinositide 3-kinase (PI3K)-p85 and hindered its nuclear translocation, eventually repressing PI3K-AKT signaling, which is essential for hippocampal neuronal proliferation., (Copyright © 2021 the authors.)