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Objective To investigate the effects of sterol regulatory element binding protein 1c (SREBP1c) deficiency on the intestinal microbiota in mice. Methods SREBP1c knockout (SREBP1c-KO) mice were used as research objects, and the feces of homozygous SREBP1c-KO mice and wild-type littermates (WT) were collected. Subsequently, the fecal genomic DNA was analyzed by 16S rDNA sequencing. The differences of gut microbial composition between the SREBP1c-KO and WT mice were detected and compared using species taxonomy analysis, diversity index analysis, cluster analysis, and principal component analysis (PCA). Moreover, the discrepancies of liver lipid anabolism and intestinal barrier were also investigated between the 2 groups. Results Under conventional feeding, SREBP1c knockout had no significant effect on the body weight and total cholesterol (TC) content in the liver of mice, but notably decreased the content of triglyceride (TG) in the liver. α diversity index (Sobs index) analysis showed that the gut microbiota diversity of SREBP1c-KO mice was greatly lower than that of the WT counterparts (P < 0.01), and PCA analysis indicated that the gut microbial composition was different between the 2 groups of mice. At the phylum level, the ratio of Firmicutes to Bacteroides presented an upward trend in the intestine of SREBP1c-KO mice, but there was no statistical difference. At the genus level, as compared with the WT group, the relative abundance of Rikenella was significantly reduced in SREBP1c-KO mice (P < 0.05). Additionally, the expression levels of intestinal barrier associated genes Reg3γ and Occludin were obviously down-regulated in SREBP1c-KO mice. Conclusion The deletion of SREBP1c, an important regulator of lipid metabolism, reduces the diversity of intestinal microbiota and the relative abundance of Rikenella in mice, which may be related to the weakening of intestinal barrier.

Objective To explore the role and underlying mechanism of microfibrillar associated protein 5 (MFAP5) in the treatment of overweight polycystic ovary syndrome (PCOS) with metformin combined with glucagon-like peptide-1 receptor agonist (GLP-1RA), liraglutides, by analyzing the correlation of the molecule alteration with improvement of metabolic indexes. Methods Twenty-three overweight or obese PCOS patients who were treated with metformin combined with liraglutide for 12 weeks in our hospital during December 2019 and February 2021 were retrospectively enrolled. According to body mass index (BMI), the subjects were divided into obese group (n=12) and overweight group (n=11). They were all given oral administration of metformin hydrochloride enteric-coated tablet (0.5 g, 3 times/day) and subcutaneous injection of liraglutide injection (primarily, 0.6 mg, once/day, and then increased to 1.2 mg, once/day, 1 week later, with the maximum dose of 1.8 mg). Physical measurement indicators, metabolic and inflammatory related indicators and sex hormone levels of the 2 groups were collected before and after 12 weeks of treatment. Plasma MFAP5 level was detected by ELISA. Results After 12 weeks of treatment, physical measurement indicators, glucose and lipid metabolism indicators, inflammatory indicators and sex hormone levels were all improved in both groups (P < 0.05). Correlation analysis showed that the alteration of plasma MFAP5 level in all patients were positively correlated with the changes of body weight (r=0.520, P=0.011), BMI (r=0.469, P=0.024), waist circumference (r=0.634, P=0.001), hip circumference (r=0.587, P=0.001), fasting insulin (r=0.602, P=0.002) and triglyceride (r=0.556, P=0.002). For the patients form the overweight group, their change of plasma MFAP5 level had a positive correlation with the changes of glucolipid metabolism related indicators, including insulin at 60 min in insulin releasing test (r=0.602, P=0.002) and triglyceride (r=0.655, P=0.029). In the obese group, the change of plasma MFAP5 level was positively correlated with the changes of waist circumference (r=0.495, P=0.002), hip circumference (r=0.508, P=0.010), glucolipid metabolism related indicators, such as fasting insulin (r=0.578, P=0.001), insulin at 180 min (r=0.656, P=0.021), HOMA-IR (r=0.497, P=0.012), triglyceride (r=0.595, P=0.041), and sex hormone. Conclusion In overweight PCOS patients, plasma MFAP5 level is related to the improvement of glucolipid metabolism. MFAP5 may be a related molecule involved in the treatment of overweight PCOS with liraylutide combined with metformin, and may serve as a reliable indicator in monitoring of therapeutic efficacy.

Since the 1950s, when the Turing Test was introduced, there has been notable progress in machine language intelligence. Language modeling, crucial for AI development, has evolved from statistical to neural models over the last two decades. Recently, transformer-based Pre-trained Language Models (PLM) have excelled in Natural Language Processing (NLP) tasks by leveraging large-scale training corpora. Increasing the scale of these models enhances performance significantly, introducing abilities like context learning that smaller models lack. The advancement in Large Language Models, exemplified by the development of ChatGPT, has made significant impacts both academically and industrially, capturing widespread societal interest. This survey provides an overview of the development and prospects from Large Language Models (LLM) to Large Multimodal Models (LMM). It first discusses the contributions and technological advancements of LLMs in the field of natural language processing, especially in text generation and language understanding. Then, it turns to the discussion of LMMs, which integrates various data modalities such as text, images, and sound, demonstrating advanced capabilities in understanding and generating cross-modal content, paving new pathways for the adaptability and flexibility of AI systems. Finally, the survey highlights the prospects of LMMs in terms of technological development and application potential, while also pointing out challenges in data integration, cross-modal understanding accuracy, providing a comprehensive perspective on the latest developments in this field. [ABSTRACT FROM AUTHOR]

Mitochondrial dynamics is the process of mitochondrial fusion and division to maintain dynamic balance. In recent years, it has been found that this dynamic change plays an important role in regulating mitochondrial morphology and quantity, mitochondrial oxidative metabolism, membrane potential and energy production. In diabetes, hyperglycemia significantly interferes with the dynamic balance of mitochondrial fusion and division process, and affects the quantity, morphology and function of mitochondria. And ultimately, the dynamic change of mitochondria is closely related to many chronic complications of diabetes, but the specific mechanism remains unclear. Our research group has long been committed to exploring the roles and mechanisms of mitochondrial dynamics in a variety of diabetic complications. This review summarizes the research progress and potential mechanisms of mitochondrial dynamics in diabetic ulcers, diabetic nephropathy and diabetic cardiomyopathy.

Podocytes are particularly sensitive to lipid accumulation, which has recently emerged as a crucial pathological process in the progression of proteinuric kidney diseases like diabetic kidney disease and focal segmental glomerulosclerosis. However, the underlying mechanism remains unclear. Here, podocytes predominantly expressed protein dedicator of cytokinesis 5 (Dock5) is screened to be critically related to podocyte lipid lipotoxicity. Its expression is reduced in both proteinuric kidney disease patients and mouse models. Podocyte‐specific deficiency of Dock5 exacerbated podocyte injury and glomeruli pathology in proteinuric kidney disease, which is mainly through modulating fatty acid uptake by the liver X receptor α (LXRα)/scavenger receptor class B (CD36) signaling pathway. Specifically, Dock5 deficiency enhanced CD36‐mediated fatty acid uptake of podocytes via upregulating LXRα in an m6A‐dependent way. Moreover, the rescue of Dock5 expression ameliorated podocyte injury and proteinuric kidney disease. Thus, the findings suggest that Dock5 deficiency is a critical contributor to podocyte lipotoxicity and may serve as a promising therapeutic target in proteinuric kidney diseases. [ABSTRACT FROM AUTHOR]