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Objective·To investigate the changes of adipose tissues in mice after high-fat diet before and during pregnancy and the potential effects on adipose tissues in their offspring.Methods·C57BL/6J female mice were randomly assigned to the normal diet (CON group, n=12) or the high-fat diet (HFD group, n=12) for 5 weeks. The two groups were further subdivided according to pregnancy: a normal diet non-pregnancy group (CON-UN group), a normal diet pregnancy group (CON-P group), a high-fat diet non-pregnancy group (HFD-UN group), and a high-fat diet pregnancy group (HFD-P group). The original diet was maintained during pregnancy and lactation. White adipose tissues (WAT) and brown adipose tissues (BAT) were collected from visceral and scapula of mice after 5 weeks of feeding or E18.5d. Offspring from both dietary groups were placed on a normal diet after weaning, and their adipose tissues were collected at the 11th week. H-E staining was used to observe the changes of adipocytes. Flow cytometry was employed to detect the proportions of CD4+T cells, CD8+T cells, total T cells, CD4+T/CD8+T and NK cells in WAT. RT-PCR was used to assess the expression of IL-6 and IL-1β mRNA in WAT.Results·After 5 weeks on a high-fat diet, the body weight of female mice in the HFD group was higher than that in the CON group (P

Objective·To analyze the effects of maternal high-fat diet on placental phenotype, and investigate the role of placental microenvironment in the intergenerational transmission.Methods·The 3-week-old C57BL/6J female mice were fed with either the high-fat diet (HFD group) or the control diet (CD group) for 5 weeks before mating and throughout gestation. Placentas and fetal liver tissues were collected from maternal mice after 20 d of gestation. The effects of maternal HFD on the placental inflammation and placental structure were investigated by hematoxylin-eosin staining (H-E staining), immunohistochemistry, Western blotting and RT-PCR. The lipid deposition levels in fetal livers were also detected. Body weight changes, fasting blood glucose and glucose tolerance levels of the 3-week-old weaned mice were also detected.Results·The body weight of female mice in the HFD group increased significantly, and the liver triacylglycerol (TAG) and total cholesterol (TC) levels were higher than those in the CD group (all P0.05). Compared to the CD group, the body weight, fasting blood glucose level and the area under the glucose tolerance curve of the 3-week-old weaned mice of the HFD group were increased significantly (all P

Aims In patients with diabetic microvascular complications, decreased perfusion or vascular occlusion, caused by reduced vascular diameter, is a common characteristic that will lead to insufficient blood supply. Yet, the regulatory mechanism and effective treatment approach remain elusive. Methods and results Our initial findings revealed a notable decrease in the expression of human AQP1 in both diabetic human retina samples (49 healthy vs. 54 diabetic samples) and high-glucose-treated human retinal microvascular endothelial cells. Subsequently, our investigations unveiled a reduction in vascular diameter and compromised perfusion within zebrafish embryos subjected to high glucose treatment. Further analysis indicated a significant down-regulation of two aquaporins, aqp1a.1 and aqp8a.1 , which are highly enriched in ECs and are notably responsive to hyperglycaemic conditions. Intriguingly, the loss of function of aqp1a.1 and/or aqp8a.1 resulted in a reduction of intersegmental vessel diameters, effectively mirroring the phenotype observed in the hyperglycaemic zebrafish model. The overexpression of aqp1a.1/aqp8a.1 in zebrafish ECs led to notable enlargement of microvascular diameters. Moreover, the reduced vessel diameters resulting from high-glucose treatment were effectively rescued by the overexpression of these aquaporins. Additionally, both aqp1a.1 and apq8a.1 were localized in the intracellular vacuoles in cultured ECs as well as the ECs of sprouting ISVs, and the loss of Aqps caused the reduction of those vacuoles, which was required for lumenization. Notably, while the loss of AQP1 did not impact EC differentiation from human stem cells, it significantly inhibited vascular formation in differentiated ECs. Conclusion EC-enriched aquaporins regulate the diameter of blood vessels through an intracellular vacuole-mediated process under hyperglycaemic conditions. These findings collectively suggest that aquaporins expressed in ECs hold significant promise as potential targets for gene therapy aimed at addressing vascular perfusion defects associated with diabetes. [ABSTRACT FROM AUTHOR]

Chronic nonhealing wounds significantly reduce patients' quality of life and are a major burden on healthcare systems. Over the past few decades, tissue engineering materials have emerged as a viable option for wound healing, with cell-derived extracellular matrix (CDM) showing remarkable results. The CDM's compatibility and resemblance to the natural tissue microenvironment confer distinct advantages to tissue-engineered scaffolds in wound repair. This review summarizes the current processes for CDM preparation, various cell decellularization protocols, and common characterization methods. Furthermore, it discusses the applications of CDM in wound healing, including skin defect and wound repair, angiogenesis, and engineered vessels, and offers perspectives on future developments. [ABSTRACT FROM AUTHOR]

The single-column model, with its advantages of low computational cost and fast execution speed, can assist users in gaining a more intuitive understanding of the impact of parameters on the simulated results of climate models. It plays a crucial role in the study of parameterization schemes, allowing for a more direct exploration of the influence of parameters on climate model simulations. In this paper, we employed various methods to conduct sensitivity analyses on the 11 parameters of the Single Column Atmospheric Model (SCAM). We explored their impact on output variables such as precipitation, temperature, humidity, and cloud cover, among others, across five test cases. To further expedite experimentation, we utilized machine learning methods to train surrogate models for the aforementioned cases. Additionally, three-parameter joint perturbation experiments were conducted based on these surrogate models to validate the combined parameter effects on the results. Subsequently, targeting the sensitive parameter combinations identified from the aforementioned experiments, we further conducted parameter tuning for the corresponding test cases to minimize the discrepancy between the results of SCAM and observational data. Our proposed method not only enhances model performance but also expedites parameter tuning speed, demonstrating good generality at the same time. [ABSTRACT FROM AUTHOR]