The earliest optimal timing for total-body 68Ga-fibroblast activation protein inhibitor-04 PET scans: an evidence-based single-centre study.

OBJECTIVES: To investigate the earliest optimal timing for positron emission tomography (PET) scans after 68Ga-fibroblast activation protein inhibitor-04 ([68Ga]Ga-FAPI-04) injection. METHODS: This prospective study enrolled patients who underwent 60-min dynamic 68Ga-FAPI-04 total-body PET/CT scans; the images were reconstructed at 10-min intervals (G0-10, G10-20, G20-30, G30-40, G40-50, and G50-60), and the [68Ga]Ga-FAPI-04 uptake patterns were evaluated. The standardised uptake value (SUV), liver signal-to-noise ratio (SNR), and lesion-to-background ratios (LBRs) for different time windows were calculated to evaluate image quality and lesion detectability. The period from 30 to 40 min was then split into overlapping 5-min intervals starting 1 min apart for further evaluation. G50-60 was considered the reference. RESULTS: A total of 30 patients with suspected malignant tumours were analysed. In the images reconstructed over 10-min intervals, longer acquisition times were associated with lower background uptake and better image quality. Some lesions could not be detected until G30-40. The lesion detection rate, uptake, and LBRs did not differ significantly among G30-40, G40-50, and G50-60 (all p > 0.05). The SUVmean and LBRs of primary tumours in the reconstructed images did not differ significantly among the 5-min intervals between 30 and 40 min; for metastatic and benign lesions, G34-39 and G35-40 showed significantly better SUVmean and LBR values than the other images. The G34-39 and G50-60 scans showed no significant differences in uptake, LBRs, or detection rates (all p > 0.05). CONCLUSION: The earliest optimal time to start acquisition was 34 min after injection of half-dose [68Ga]Ga-FAPI-04. CLINICAL RELEVANCE STATEMENT: This study evaluated 68Ga-fibroblast activation protein inhibitor-04 ([68Ga]Ga-FAPI-04) uptake patterns by comparing the image quality and lesion detection rate with 60-min dynamic [68Ga]Ga-FAPI-04 total-body PET/CT scans and identified the earliest optimal scan time after [68Ga]Ga-FAPI-04 injection. KEY POINTS: • A prospective single-centre study showed that the earliest optimal time point to start acquisition was 34 min after injection of half-dose [68Ga-fibroblast activation protein inhibitor-04 (68Ga]Ga-FAPI-04). • There were statistically significant differences in standardised uptake value, lesion-to-background ratios, and lesion detectability between scans before and after 34 min from the injection of [68Ga]Ga-FAPI-04, but these values did not change further from 34 to 60 min after injection. • With a reasonable acquisition time, the image quality could still meet diagnostic requirements.

Effects of Adipose Tissue-Specific Knockout of Delta-like Non-Canonical Notch Ligand 1 on Lipid Metabolism in Mice.

Delta-like non-canonical Notch ligand 1 (DLK1), which inhibits the differentiation of precursor adipocytes, is a recognized marker gene for precursor adipocytes. Lipids play a crucial role in energy storage and metabolism as a vital determinant of beef quality. In this study, we investigated the mechanism of the DLK1 gene in lipid metabolism by constructing adipose tissue-specific knockout mice. We examined some phenotypic traits, including body weight, liver coefficient, fat index, the content of triglyceride (TG) and cholesterol (CHOL) in abdominal white adipose tissue (WAT) and blood. Subsequently, the fatty acid content and genes related to lipid metabolism expression were detected in DLK1-/- and wild-type mice via GC-MS/MS analysis and quantitative real-time PCR (qRT-PCR), respectively. The results illustrated that DLK1-/- mice exhibited significant abdominal fat deposition compared to wild-type mice. HE staining and immunohistochemistry (IHC) results showed that the white adipocytes of DLK1-/- mice were larger, and the protein expression level of DLK1-/- was significantly lower. Regarding the blood biochemical parameters of female mice, DLK1-/- mice had a strikingly higher triglyceride content (p < 0.001). The fatty acid content in DLK1-/- mice was generally reduced. There was a significant reduction in the expression levels of the majority of genes that play a crucial role in lipid metabolism. This study reveals the molecular regulatory mechanism of fat metabolism in mice and provides a molecular basis and reference for the future application of the DLK1 gene in the breeding of beef cattle with an excellent meat quality traits. It also provides a molecular basis for unravelling the complex and subtle relationship between adipose tissue and health.

Assessing the causal relationship between frailty and sex hormone-binding globulin or insulin-like growth factor-1 levels: A sex-stratified bidirectional Mendelian Randomization study.

BACKGROUND: The association between frailty and sex hormone-binding globulin (SHBG) or insulin-like growth factor-1(IGF-1) levels demonstrates sex differences with inconsistent conclusions. This study aims to explore the causal relationship between frailty and SHBG or IGF-1 levels through bidirectional Mendelian randomization (MR). METHODS: We conducted two-sample bidirectional sex-stratified MR analyses using summary-level data from genome-wide association studies (GWASs) to examine the causal relationship between frailty and IGF-1 or SHBG levels, as measured by frailty index (FI) and frailty phenotype (FP). We use the random-effects inverse-variance weighted (IVW), weighted median, MR-Egger, MR-Egger intercept, and leave-one-out approaches. RESULT: The relationship between frailty and SHBG or IGF-1 levels is inversely related, with a significant decrease in SHBG levels in females. Specifically, SHBG levels significantly decrease with FI (ß = -5.49; 95 % CI: -9.67 to -1.32; FDR = 0.02) and more pronounced with FP (ß = -10.14; 95 % CI: -16.16 to -4.13; FDR = 0.01), as determined by the IVW approach. However, reverse analysis shows no significant effect of IGF-1 or SHBG levels on either FI or FP (p > 0.05). CONCLUSION: Our study indicates a negative correlation between frailty and the levels of SHBG and IGF-1. It is suggested that further research is required to establish cut-off values for SHBG and IGF-1 levels in the frailty population. This is particularly important for females at higher risk, such as those undergoing menopause, to enable comprehensive assessment and early prevention efforts. While the findings imply that reduced IGF-1 and SHBG levels may not directly contribute to frailty, it is important not to overlook the underlying mechanisms through which they may indirectly influence frailty.

Polymorphisms of the SCD1 Gene and Its Association Analysis with Carcass, Meat Quality, Adipogenic Traits, Fatty Acid Composition, and Milk Production Traits in Cattle.

Stearoyl-CoA desaturase-1 (SCD1) is a key enzyme in the biosynthesis of monounsaturated fatty acids and is considered a candidate gene for improving milk and meat quality traits. Sanger sequencing was employed to investigate the genetic polymorphism of the fifth exon and intron of bovine SCD1, revealing four SNPs, g.21272246 A>G, g.21272306 T>C, g.21272422 C>T, and g.21272529 A>G. Further variance analysis and multiple comparisons were conducted to examine the relationship between variation sites and economic traits in Chinese Simmental cattle, as well as milk production traits in Holstein cows. The findings revealed these four loci exhibited significant associations with carcass traits (carcass weight, carcass length, backfat thickness, and waist meat thickness), meat quality (pH value, rib eye area, and marbling score), adipogenic traits (fat score and carcass fat coverage rate), and fatty acid composition (linoleic acid and α-linolenic acid). Furthermore, these loci were additionally found to be significantly associated with average milk yield and milk fat content in cows. In addition, a haplotype analysis of combinations of SNPs showed that H2H3 has a significant association with adipogenic traits and H2H2 was associated with higher levels of linoleic acid and α-linolenic acid than the other combinations. These results suggest that the four SNPs are expected to be prospective genetic markers for the above economic traits. In addition, the function of SNPs in exon 5 of SCD1 on gene expression and protein structure needs to be explored in the future.

Lipid Regulatory Element Interact with CD44 on Mitochondrial Bioenergetics in Bovine Adipocyte Differentiation and Lipometabolism.

The CD44 gene is a critical factor in animal physiological processes and has been shown to affect insulin resistance and fat accumulation in mammals. Nevertheless, little research has been conducted on its precise functions in lipid metabolism and adipogenic differentiation in beef cattle. This study analyzed the expression of CD44 and miR-199a-3p during bovine preadipocyte differentiation. The luciferase reporter assay demonstrated that CD44 was a direct target of miR-199a-3p. Increased accumulation of lipid droplets and triglyceride levels, altered fatty acid metabolism, and accelerated preadipocyte differentiation were all caused by the upregulation of miR-199a-3p or a reduction in CD44 expression. CD44 knockdown upregulated the expression of adipocyte-specific genes (LPL and FABP4) and altered the levels of lipid metabolites (SOPC, l-arginine, and heptadecanoic acid). Multiomics highlights enriched pathways involved in energy metabolism (MAPK, cAMP, and calcium signaling) and shifts in mitochondrial respiration and glycolysis, indicating that CD44 plays a regulatory role in lipid metabolism. The findings show that intracellular lipolysis, glycolysis, mitochondrial respiration, fat deposition, and lipid droplet composition are all impacted by miR-199a-3p, which modulates CD44 in bovine adipocytes.