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Abstract As a remarkably specific characteristic of breast cancer observed on magnetic resonance imaging (MRI), the association between the NME type breast cancer and prognosis, including Ki-67, necessitates comprehensive exploration. To investigate the correlation between dynamic contrast-enhanced MRI (DCE-MRI) characteristics and apparent diffusion coefficient (ADC) values with Ki-67-positive expression in NME type breast cancer. A total of 63 NME type breast cancer patients were retrospectively reviewed. Malignancies were confirmed by surgical pathology. All patients underwent DCE and diffusion-weighted imaging (DWI) before surgery. DCE-MRI characteristics, including tumor distribution, internal enhancement pattern, axillary adenopathy, and time-intensity curve types were observed. ADC values and lesion sizes were also measured. The correlation between these features and Ki-67 expression were assessed using Chi-square test, Fisher’s exact test, and Spearman rank analysis. The receiver operating characteristic curve and area under the curve (AUC) was used to evaluate the diagnostic performance of Ki-67-positive expression. Regional distribution, TIC type, and ipsilateral axillary lymph node enlargement were correlated with Ki-67-positive expression (χ 2 = 0.397, 0.357, and 0.357, respectively; P

Tetrahydrobiopterin (BH4) is a vital coenzyme for several enzymes involved in diverse enzymatic reactions in animals, and BH4 deficiency can lead to metabolic and neurological disorders due to dysfunction in its metabolism. In the silkworm natural homozygous mutant leml, the key enzyme sepiapterin reductase (BmSPR) in the de novo synthesis pathway of BH4 is inactivated, resulting in severe deficiency of BH4 synthesis. However, it is not known why the leml larvae can survive to the second-instar stage and which pathways lead to their death when BH4 is deficient. Here, we quantified BH4 and found that the fertilized eggs contained large amounts of BH4 transferred from the mother to the offspring, maintaining its normal development in the embryo and the first instar. Subsequently, we investigated the multiple pathways in which BH4 is involved as a cofactor. The results showed that BH4 deficiency in silkworms blocked the melanin synthesis pathway, caused an insufficient degree of epidermal sclerosis, disordered tyrosine metabolism, and damaged mitochondria. On the other hand, BH4 deficiency led to the uncoupling of nitric oxide synthase (BmNOS), a reduced NO production, and a significantly reduced fat in fat body catalyzation by phospholipase A2, resulting in an impaired immune system. Meanwhile, the uncoupling of BmNOS increased the O2− content, damaged the DNA, and caused the apoptosis of the body cells. Taken together, BH4 is critical for the life and death of leml mutants. This study lays a foundation for the further exploration of lepidopteran insects and provides an important basis for the treatment of human BH4 deficiency-related diseases.