Spatial resolved transcriptomics reveals distinct cross-talk between cancer cells and tumor-associated macrophages in intrahepatic cholangiocarcinoma.

BACKGROUND: Multiple studies have shown that tumor-associated macrophages (TAMs) promote cancer initiation and progression. However, the reprogramming of macrophages in the tumor microenvironment (TME) and the cross-talk between TAMs and malignant subclones in intrahepatic cholangiocarcinoma (iCCA) has not been fully characterized, especially in a spatially resolved manner. Deciphering the spatial architecture of variable tissue cellular components in iCCA could contribute to the positional context of gene expression containing information pathological changes and cellular variability. METHODS: Here, we applied spatial transcriptomics (ST) and digital spatial profiler (DSP) technologies with tumor sections from patients with iCCA. RESULTS: The results reveal that spatial inter- and intra-tumor heterogeneities feature iCCA malignancy, and tumor subclones are mainly driven by physical proximity. Tumor cells with TME components shaped the intra-sectional heterogenetic spatial architecture. Macrophages are the most infiltrated TME component in iCCA. The protein trefoil factor 3 (TFF3) secreted by the malignant subclone can induce macrophages to reprogram to a tumor-promoting state, which in turn contributes to an immune-suppressive environment and boosts tumor progression. CONCLUSIONS: In conclusion, our description of the iCCA ecosystem in a spatially resolved manner provides novel insights into the spatial features and the immune suppressive landscapes of TME for iCCA.

Segmentation of Uterus Using Laparoscopic Ultrasound by an Image-Based Active Contour Approach for Guiding Gynecological Diagnosis and Surgery.

In laparoscopic gynecologic surgery, ultrasound has been typically implemented to diagnose urological and gynecological conditions. We applied laparoscopic ultrasonography (using Esaote 7.5~10MHz laparoscopic transducer) on the retrospective analyses of 42 women subjects during laparoscopic extirpation and excision of gynecological tumors in our hospital from August 2011 to August 2013. The objective of our research is to develop robust segmentation technique for isolation and identification of the uterus from the ultrasound images, so as to assess, locate and guide in removing the lesions during laparoscopic operations. Our method enables segmentation of the uterus by the active contour algorithm. We evaluated 42 in-vivo laparoscopic images acquired from the 42 patients (age 39.1 ± 7.2 years old) and selected images pertaining to 4 cases of congenital uterine malformations and 2 cases of pelvic adhesions masses. These cases (n = 6) were used for our uterus segmentation experiments. Based on them, the active contour method was compared with the manual segmentation method by a medical expert using linear regression and the Bland-Altman analysis (used to measure the correlation and the agreement). Then, the Dice and Jaccard indices are computed for measuring the similarity of uterus segmented between computational and manual methods. Good correlation was achieved whereby 84%-92% results fall within the 95% confidence interval in the Student t-test) and we demonstrate that the proposed segmentation method of uterus using laparoscopic images is effective.

Base substitution mutations in uridinediphosphate-dependent glycosyltransferase 76G1 gene of Stevia rebaudiana causes the low levels of rebaudioside A: mutations in UGT76G1, a key gene of steviol glycosides synthesis.

Steviol glycosides, extracted from the leaves of Stevia rebaudiana (Bert) Bertoni, are calorie-free sugar substitute of natural origin with intensely sweet (Boileau et al., 2012). Stevioside and rebaudioside A are the two main kinds of the diterpenic glycosides. We analyzed the concentration of stevioside and rebaudioside A in Stevia leaves of about 500 samples (hybrid progenies) and discovered a mutation plant "Z05" with very low levels of rebaudioside A. Because UGT76G1, a uridinediphosphate-dependent glycosyltransferases, is responsible for the conversion from stevioside to rebaudioside A (Richman et al., 2005), so mutation identification was done by sequencing the candidate gene, UGT76G1. In this study molecular analysis of two strains revealed a heterozygotic nonsense mutation of c.389T > G (p.L121X) in UGT76G1. Meanwhile, we found some amino acid substitutions significant change the protein structure. And the difference of enzyme activity between two strains proved the lack of functionality of UGT76G1 of the mutation "Z05". So the nonsense mutation and amino acid substitution mutation resulted in the low levels of rebaudioside A.