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At the request of the corresponding author, the JCI is retracting this article. Following an institutional investigative review of errors in the article, it was determined that the data reported in Figure 1B were an analysis of E2F1 expression rather than CERS6 expression, as originally reported. The correct data do not show a difference in CERS6 expression with invasion status in human lung adenocarcinomas. In addition, errors were noted in Supplemental Figure 2, Supplemental Figure 3B, and Supplemental Table 1. The institutional review found no evidence of intention to falsify results.

γ-Aminobutyrate (GABA) is commonly used as a food supplement and a health care product by young females, due to its positive roles in relieving stress, alleviating anxiety, and improving sleep. However, its recommended daily dose in different products varies widely. Besides, it is unknown whether, and how, GABA consumption during early pregnancy influences pregnancy establishment. In this study, we found that when pregnant mice were treated with a high (12.5 mg/g) dose of GABA (orally) during preimplantation, there was a reduction in the number of implantation sites on day 5 of pregnancy. Also, among these unimplanted embryos, most exhibited morphological degeneration and developmental retardation, and only a few of them developed into blastocysts but could not implant into the uterus. Moreover, the expression of uterine receptivity-related factors-LIF, E-cadherin, and HOXA10were all downregulated, while the number of uterine glands was reduced in the high GABA dose group. Finally, in vitro results demonstrated that GABA (ranging from 10 to 50 μg/μL) markedly inhibited preimplantation embryo development in a doseresponse manner. However, this inhibitory effect was not observed when the embryos were pretreated with 40 μΜ 2-hydroxysaclofen, a GABA B antagonist, indicating that GABA exerts its inhibitory effects via its B-type receptor. Our results suggest that exposure to certain GABA concentrations, during early pregnancy, can impair preimplantation embryo development via its B-type receptor, and endometrial receptivity, which greatly disturbs early embryo implantation in mice. These findings could raise concerns about GABA consumption during the early stages of pregnancy. K E Y W O R D S blastocyst formation, embryo implantation, embryonic development, endometrial receptivity, GABA

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The aim of this study was to investigate the synergistic antitumor activity of rhein and doxorubicin (DOX) and to elucidate the underlying mechanisms in hepatocellular SMMC‐7721 and HepG2 cells. Cell growth curves, caspase‐3 activity, and intracellular DOX accumulation were observed using an IncuCyte real‐time video imaging system. Combination index was used to calculate synergistic potential of rhein and DOX. Cell apoptosis was detected by the Annexin V‐FITC/PI apoptosis kit. Lactate dehydrogenase and adenosine triphosphate (ATP) levels were assessed using an assay kit. Oxygen consumption rates (OCR) and extracellular acidification rates were assessed by the Seahorse XFe96 Extracellular Flux Analyzer. Mitochondrial inner membrane potential (ΔΨm) was monitored with JC‐1 fluorescence. Western blot analysis was used to detect the level of P‐glycoprotein. Synergistic antiproliferative and proapoptotic effects were exerted by the combination of rhein at 10 μM and DOX at 2 μM in SMMC‐7721 and HepG2 cells. Rhein could influenced the accumulation of DOX in both cells, which was associated with remarkably decreased mitochondrial energy metabolism and ATP levels. Rhein could reduce ΔΨm in both cells. mPTP, opener atractyloside (ATR) could accelerate the loss of ΔΨm, and further suppress the OCR induced by rhein. In contrast, the mPTP blocker cyclosporin A (Cs A) inhibited the loss of ΔΨm and the OCR induced by rhein. Our data indicate that a decline in mitochondrial energy metabolism was responsible for the synergistic antitumor effects of rhein and DOX in hepatocellular carcinoma cells. Reduction of ΔΨm and opening of mPTP inhibited the exchange of ATP/adenosine diphosphate between mitochondrial matrix and cytoplasm is the important mechanism.

Melanoma-associated antigens (MAGEs) are a group of well-characterized members of the cancer/testis antigen family, which are expressed in a variety of malignant tumors. MAGE-A9, a subfamily of MAGE-As, has been studied in a number of types of cancer and have been associated with unfavorable survival outcome. However, the expression of MAGE-A9 in human esophageal squamous cell carcinoma (ESCC) and association of MAGE-A9 with the clinicopathological characteristics of ESCC, particularly prognostic characteristics, remains unknown. The present study aimed at determining the expression level of MAGE-A9 and at evaluating its clinical significance in human ESCC. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) analyses were performed to characterize the expression of MAGE-A9 in ESCC tissues. Kaplan-Meier estimator survival and Coxs regression analyses were used to evaluate the prognosis of 103 patients with ESCC. The results of qPCR and IHC analysis revealed that the expression of MAGE-A9 was significantly increased in ESCC tissues, compared with that in healthy tissues. Furthermore, the expression level of MAGE-A9 protein in ESCC was significantly associated with the pathological grade (P=0.008), tumor size (P=0.027) and lymph node metastasis (P=0.009). Multivariate analysis using Coxs regression model identified that the expression level of MAGE-A9 and lymph node metastasis were independent prognostic factors for the overall survival rate of patients with ESCC (P=0.006 and P=0.001, respectively). The results of the present study are, to the best of our knowledge, the first to indicate that MAGE-A9 expression is a valuable prognostic biomarker for ESCC and that it may serve as a targeted therapy in the treatment of ESCC. Increased expression of MAGE-A9 indicated an unfavorable survival outcome in patients with ESCC.

Original citation: J Clin Invest. 2016;126(1):254-265. https://doi.org/10.1172/JCI79775. Citation for this expression of concern: J Clin Invest. 2019;129(8):3464. https://doi.org/10.1172/JCI131245. The corresponding author recently notified the JCI that the patient data presented in Figure 1B were not correct. Analysis of the correct patient data set does not show a significant difference in CERS6 expression in human lung adenocarcinomas with positive invasive growth (definite) compared with those with negligible invasive growth or without invasive growth (focal/none). The Editors have requested an institutional investigation into this matter, and we will inform our readers of the outcome when the investigation is complete. Original citation: J Clin Invest. 2016;126(8):3036-3052. https://doi.org/10.1172/JCI83416.Citation for this expression of concern: J Clin Invest. 2019;129(8):3464. https://doi.org/10.1172/JCI131246. A reader recently alerted the Journal that two images in this JCI article appear similar to images subsequently published in a Neuro-Oncology paper from the same lab as unique samples (1). Specifically, in Figure 9D of the JCI paper, the image for IL13Rα2 staining for the HER2 CAR sample appears to be similar to the image for EphA2 staining of a nontransduced T cell-treated sample published in Figure 6A of the Neuro-Oncology paper. In addition, in Figure 9D of the JCI paper, the image for IL13Rα2 staining for the tumor sample appears to be similar to the image for HER2 staining of a nontransduced T cell-treated sample in Figure 6B of the Neuro-Oncology paper. An institutional investigation into this matter is ongoing, and we will inform our readers of the outcome when the investigation is complete.