Detachment Activated CyPA/CD147 Induces Cancer Stem Cell Potential in Non-stem Breast Cancer Cells

This work is licensed under a Creative Commons Attribution 4.0 International License.Background: Cancer stem cells (CSCs), responsible for cancer metastasis and recurrence, are generated from non-CSCs after chemo-radiation therapy. This study investigated the induction of CSC potential in non-stem breast cancer cells and the underlying molecular mechanisms in detachment culture. Methods: Bulk breast cancer cells, or sorted non-CSCs and CSCs were cultured under an attached or detached condition to assess CSC numbers, ability to form tumor spheres, expression of stemness markers, and chemoresistance. Lentivirus carrying CD147 shRNA or cDNA was used to manipulate CD147 expression, while CD147 ligand recombinant cyclophilin A (CyPA) or its inhibitor was used to activate or inhibit CD147 signaling. Results: Detachment promoted anoikis resistance, chemoresistance, sphere formation, self-renewal, and expression of stemness markers in breast cancer cells. Detachment increased functional ALDH+ or CD44highCD24–/low CSCs, and induced CSC potential in ALDH– or CD44lowCD24high non-CSCs. Upon detachment, both CD147 expression and CyPA secretion were enhanced, and CyPA-CD147 activation mediated detachment induced CSC potential in non-CSCs via STAT3 signaling. Clinically, CD147 and pSTAT3 were highly co-expressed and correlated with poor overall survival and tumor recurrence in breast cancer patients. Conclusion: This study demonstrates that detachment induces the generation of CSCs from non-stem breast cancer cells via CyPA-CD147 signaling, indicating that targeting CD147 may serve as a potential novel therapeutic strategy for lethal metastatic breast cancer by eliminating induced CSCs.National Basic Research Program (#2015CB553700)National Science and Technology Major Project (#2015ZX09501-009)National Natural Science Foundation of China (#31571469 and #81872349

Heart rate patterns of captive Asian elephant (Elephas maximus) in their natural habitat at Wild Elephant Valley, Xishuangbanna of China

There are few studies on the changes of heart rate of the Asian elephant (Elephas maximus), one of the largest tropical terrestrial mammals, with its self-factors and external environment. By measuring the heart rate of 35 Asian elephants, ranging in age from 4 months to 52 years, using a non-invasive electrocardiogram sensor in their natural habitat at Wild Elephant Valley, Xishuangbanna of China, we found factors that significantly influenced the HR were season, phase of the day, age, body weight, and the interaction between some of the above factors. We also observed that Asian elephants had lower resting heart rate in the morning of hot season than the cold and mild season, and the differences were significant, but the heart rate increased to similar levels in the afternoon regardless of the season. HR also decreased with age in all seasons and phases of the day. However, there was no significant effect of sex. This study reveals the adaptability of Asian elephant to tropical environment, and provides a basic reference for heart rate of Asian elephant under various natural conditions

Transperitoneal vs retroperitoneal laparoscopic radical nephrectomy: a double-arm, parallel-group randomized clinical trial

Abstract Objective To compare the outcomes of patients undergoing Retroperitoneal laparoscopic Radical nephrectomy (RLRN) and Transperitoneal laparoscopic Radical nephrectomy (TLRN). Methods A total of 120 patients with localized renal cell carcinoma were randomized into either RLRN or TLRN group. Mainly by comparing the patient perioperative related data, surgical specimen integrity, pathological results and tumor results. Results Each group comprised 60 patients. The two group were equivalent in terms of perioperative and pathological outcomes. The mean integrity score was significantly lower in the RLRN group than TLRN group. With a median follow-up of 36.4 months after the operation, Kaplan–Meier survival analysis showed no significant difference between RLRN and TLRN in overall survival (89.8% vs. 88.5%; P = 0.898), recurrence-free survival (77.9% vs. 87.7%; P = 0.180), and cancer-specific survival (91.4% vs. 98.3%; P = 0.153). In clinical T2 subgroup, the recurrence rate and recurrence-free survival in the RLRN group was significantly worse than that in the TLRN group (43.2% vs. 76.7%, P = 0.046). Univariate and multivariate COX regression analysis showed that RLRN (HR: 3.35; 95%CI: 1.12–10.03; P = 0.030), male (HR: 4.01; 95%CI: 1.07–14.99; P = 0.039) and tumor size (HR: 1.23; 95%CI: 1.01–1.51; P = 0.042) were independent risk factor for recurrence-free survival. Conclusions Our study showed that although RLRN versus TLRN had roughly similar efficacy, TLRN outperformed RLRN in terms of surgical specimen integrity. TLRN was also significantly better than RLRN in controlling tumor recurrence for clinical T2 and above cases. Trial registration Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=24400 ), identifier: ChiCTR1800014431, date: 13/01/2018

Additional file 1 of Transperitoneal vs retroperitoneal laparoscopic radical nephrectomy: a double-arm, parallel-group randomized clinical trial

Additional file 1: Supplementary Table 1. Univariate and multivariate analysis of recurrence-free survival in patients with clinical T2 stage RCC

Bug mapping and fitness testing of chemically synthesized chromosome X

Debugging a genome sequence is imperative for successfully building a synthetic genome. As part of the effort to build a designer eukaryotic genome, yeast synthetic chromosome X (synX), designed as 707,459 base pairs, was synthesized chemically. SynX exhibited good fitness under a wide variety of conditions. A highly efficient mapping strategy called pooled PCRTag mapping (PoPM), which can be generalized to any watermarked synthetic chromosome, was developed to identify genetic alterations that affect cell fitness (“bugs”). A series of bugs were corrected that included a large region bearing complex amplifications, a growth defect mapping to a recoded sequence in FIP1, and a loxPsym site affecting promoter function of ATP2. PoPM is a powerful tool for synthetic yeast genome debugging and an efficient strategy for phenotype-genotype mapping