zDHHC3-mediated S-palmitoylation of SLC9A2 regulates apoptosis in kidney clear cell carcinoma.

PURPOSE: Kidney clear cell carcinoma (KIRC) has a poor prognosis, high morbidity and mortality rates, and high invasion and metastasis rate, and effective therapeutic targets are lacking. zDHHC3 has been implicated in various cancers, but its specific role in KIRC remains unclear. METHODS: In this study, we performed a pan-cancer analysis, bioinformatics analysis, and cell experiment to detect the role of zDHHC3 in KIRC. RESULTS: zDHHC3 was significantly down-regulated in KIRC, and that its high expression was associated with favorable patient outcomes. We identified 202 hub genes that were most relevant to high zDHHC3 expression and KIRC, and found that they were involved mainly in ion transport and renal cell carcinoma. Among these hub genes, SLC9A2 was identified as a downstream gene of zDHHC3. zDHHC3 suppression led to decreased expression and S-palmitoylation of SLC9A2, which further inhibited the apoptosis of Caki-2 cells. CONCLUSION: Our findings suggest that zDHHC3 plays an important role in KIRC, due partly to its regulation of SLC9A2 S-palmitoylation. The targeting of the zDHHC3-SLC9A2 axis may provide a new option for the clinical treatment of KIRC.

The vasculogenic mimicry related signature predicts the prognosis and immunotherapy response in renal clear cell carcinoma.

BACKGROUND: Clear cell carcinoma of the kidney is a common urological malignancy characterized by poor patient prognosis and treatment outcomes. Modulation of vasculogenic mimicry in tumor cells alters the tumor microenvironment and the influx of tumor-infiltrating lymphocytes, and the combination of its inducers and immune checkpoint inhibitors plays a synergistic role in enhancing antitumor effects. METHODS: We downloaded the data from renal clear cell carcinoma samples and vasculogenic mimicry-related genes to establish a new vasculogenic mimicry-related index (VMRI) using a machine learning approach. Based on VMRI, patients with renal clear cell carcinoma were divided into high VMRI and low VMRI groups, and patients' prognosis, clinical features, tumor immune microenvironment, chemotherapeutic response, and immunotherapeutic response were systematically analyzed. Finally, the function of CDH5 was explored in renal clear cell carcinoma cells. RESULTS: VMRI can be used for prognostic and immunotherapy efficacy prediction in a variety of cancers, which consists of four vasculogenic mimicry-related genes (CDH5, MMP9, MAPK1, and MMP13), is a reliable predictor of survival and grade in patients with clear cell carcinoma of the kidney and has been validated in multiple external datasets. We found that the high VMRI group presented higher levels of immune cell infiltration, which was validated by pathological sections. We performed molecular docking prediction of vasculogenic mimicry core target proteins and identified natural small molecule drugs with the highest affinity for the target protein. Knockdown of CDH5 inhibited the proliferation and migration of renal clear cell carcinoma. CONCLUSIONS: The VMRI identified in this study allows for accurate prognosis assessment of patients with renal clear cell carcinoma and identification of patient populations that will benefit from immunotherapy, providing valuable insights for future precision treatment of patients with renal clear cell carcinoma.

KLF transcription factors in bone diseases.

Krüppel-like factors (KLFs) are crucial in the development of bone disease. They are a family of zinc finger transcription factors that are unusual in containing three highly conserved zinc finger structural domains interacting with DNA. It has been discovered that it engages in various cell functions, including proliferation, apoptosis, autophagy, stemness, invasion and migration, and is crucial for the development of human tissues. In recent years, the role of KLFs in bone physiology and pathology has received adequate attention. In addition to regulating the normal growth and development of the musculoskeletal system, KLFs participate in the pathological process of the bones and joints and are intimately linked to several skeletal illnesses, such as osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis (OP) and osteosarcoma (OS). Consequently, targeting KLFs has emerged as a promising therapeutic approach for an array of bone disorders. In this review, we summarize the current literature on the importance of KLFs in the emergence and regulation of bone illnesses, with a particular emphasis on the pertinent mechanisms by which KLFs regulate skeletal diseases. We also discuss the need for KLFs-based medication-targeted treatment. These endeavours offer new perspectives on the use of KLFs in bone disorders and provide prognostic biomarkers, therapeutic targets and possible drug candidates for bone diseases.

Drug resistance in ovarian cancer: from mechanism to clinical trial.

Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance is the bottleneck in ovarian cancer treatment. The increasing use of novel drugs in clinical practice poses challenges for the treatment of drug-resistant ovarian cancer. Continuing to classify drug resistance according to drug type without understanding the underlying mechanisms is unsuitable for current clinical practice. We reviewed the literature regarding various drug resistance mechanisms in ovarian cancer and found that the main resistance mechanisms are as follows: abnormalities in transmembrane transport, alterations in DNA damage repair, dysregulation of cancer-associated signaling pathways, and epigenetic modifications. DNA methylation, histone modifications and noncoding RNA activity, three key classes of epigenetic modifications, constitute pivotal mechanisms of drug resistance. One drug can have multiple resistance mechanisms. Moreover, common chemotherapies and targeted drugs may have cross (overlapping) resistance mechanisms. MicroRNAs (miRNAs) can interfere with and thus regulate the abovementioned pathways. A subclass of miRNAs, "epi-miRNAs", can modulate epigenetic regulators to impact therapeutic responses. Thus, we also reviewed the regulatory influence of miRNAs on resistance mechanisms. Moreover, we summarized recent phase I/II clinical trials of novel drugs for ovarian cancer based on the abovementioned resistance mechanisms. A multitude of new therapies are under evaluation, and the preliminary results are encouraging. This review provides new insight into the classification of drug resistance mechanisms in ovarian cancer and may facilitate in the successful treatment of resistant ovarian cancer.

Clinical analysis of nonsyndromic oligodontia phenotypes.

OBJECTIVES: To provide references, this study investigated the clinical characteristics of patients with nonsyndromic oligodontia. METHODS: The information of 178 patients with oligodontia was collected, including histories, oral examinations, and panoramic radiographs. Tooth agenesis characteristics were calculated and evaluated. All the data were statistically analyzed with SPSS 24.0 software. RESULTS: No significant difference in the number of missing teeth was found between sexes nor between the right and left sides, and congenitally missing teeth affected the maxillary arch (P<0.05). The highest prevalence of tooth agenesis was observed in the mandibular second premolars. In the maxillary arch, the most common pattern of tooth agenesis was agenesis of the bilateral first and second premolars. The agenesis of the bilateral second premolars was observed in the mandibular arch. The prevalence of a symmetric pattern between the right and left quadrants was significantly higher than that of matched patterns between the maxillary and mandibular antagonistic quadrants. Approximately 16.85% of patients with nonsyndromic oligodontia were affected by other tooth-related anomalies. CONCLUSIONS: The common patterns of tooth agenesis were successfully identified in patients with nonsyndromic oligodontia. Dentists need to provide multidisciplinary treatments for patients with nonsyndromic oligodontia because of variations in occluding and full-mouth tooth agenesis patterns.

Integrative analysis of single-cell and bulk RNA-sequencing data revealed disulfidptosis genes-based molecular subtypes and a prognostic signature in lung adenocarcinoma.

BACKGROUND: Disulfidoptosis is an unconventional form of programmed cell death that distinguishes itself from well-established cell death pathways like ferroptosis, pyroptosis, and necroptosis. METHODS: Initially, we conducted a single-cell analysis of the GSE131907 dataset from the GEO database to identify disulfidoptosis-related genes (DRGs). We utilized differentially expressed DRGs to classify TCGA samples with an unsupervised clustering algorithm. Prognostic models were built using Cox regression and LASSO regression. RESULTS: Two DRG-related clusters (C1 and C2) were identified based on the DEGs from single-cell sequencing data analysis. In comparison to C1, C2 exhibited significantly worse overall prognosis, along with lower expression levels of immune checkpoint genes (ICGs) and chemoradiotherapy sensitivity-related genes (CRSGs). Furthermore, C2 displayed a notable enrichment in metabolic pathways and cell cycle-associated mechanisms. C2 was also linked to the development and spread of tumors. We created a prognostic risk model known as the DRG score, which relies on the expression levels of five DRGs. Patients were categorized into high-risk and low-risk groups depending on their DRG score, with the former group being linked to a poorer prognosis and higher TMB score. Moreover, the DRG score displayed significant correlations with CRSGs, ICGs, the tumor immune dysfunction and exclusion (TIDE) score, and chemotherapeutic sensitivity. Subsequently, we identified a significant correlation between the DRG score and monocyte macrophages. Additionally, crucial DRGs were additionally validated using qRT-PCR. CONCLUSIONS: Our new DRG score can predict the immune landscape and prognosis of LUAD, serving as a reference for immunotherapy and chemotherapy.

Disclosing phototransformation mechanisms of decabromodiphenyl ether (BDE-209) in different media by simulated sunlight: Implication by compound-specific stable isotope analysis.

As one of the typical brominated flame retardants, decabromodiphenyl ether (BDE-209) has been widely detected in environment. However, scarce information was available on BDE-209 phototransformation mechanisms in various media. In this study, compound-specific stable isotope analysis was first applied to investigate BDE-209 phototransformation in n-hexane, MeOH:H2O (v:v, 8:2), and simulated seawater by simulated sunlight. BDE-209 transformation followed pseudo-first-order kinetic, with degradation rate in the following of n-hexane (2.66 × 10-3 min-1) > simulated seawater (1.83 × 10-3 min-1) > MeOH:H2O (1.41 × 10-3 min-1). Pronounced carbon isotope fractionation was first observed for BDE-209 phototransformation, with carbon isotope enrichment factors (εC) of -1.01 ± 0.14‰, -1.77 ± 0.26‰, -2.94 ± 0.38‰ in n-hexane, MeOH:H2O and simulated seawater, respectively. Combination analysis of products and stable carbon isotope, debromination with cleavage of C-Br bonds as rate-limiting step was the main mechanism for BDE-209 phototransformation in n-hexane, debromination and hydroxylation with cleavage of C-Br bonds as rate-limiting steps in MeOH:H2O, and debromination, hydroxylation and chlorination in simulated seawater. This present study confirmed that stable carbon isotope analysis was a robust method to discovery the underlying phototransformation mechanisms of BDE-209 in various solutions.

lncRNA CYTOR promotes lung adenocarcinoma gemcitabine resistance and epithelial-mesenchymal transition by sponging miR-125a-5p and upregulating ANLN and RRM2.

Lung adenocarcinoma (LUAD) is one of the most aggressive types of lung cancer. The prognosis of LUAD patients remains poor, and the overall efficacy of gemcitabine-based chemotherapy is still unsatisfactory. Long noncoding RNAs (lncRNAs) play important roles in several cancer types by interacting with multiple proteins, RNA, and DNA. However, the relationship between lncRNA dysregulation and gemcitabine resistance in LUAD has not been fully elucidated. In this study, lncRNA CYTOR expression and its association with the prognosis of LUAD patients are assessed by quantitative RT-PCR and Kaplan-Meier survival analysis. In vitro and in vivo functional studies are conducted to evaluate the biological functions of CYTOR in LUAD. The underlying mechanism regarding the tumor-promoting effects of CYTOR is explored using RNA immunoprecipitation, biotin-labelled RNA pulldown, luciferase reporter assays, and western blot analysis. We identify that CYTOR is an oncogenic lncRNA and is apparently upregulated in LUAD by analysing TCGA-LUAD data. High CYTOR expression is a poor prognostic factor for LUAD. Functional studies reveal that CYTOR confers LUAD cells with stronger resistance to gemcitabine treatment and upregulates the expression levels of epithelial-mesenchymal transition (EMT)-related proteins. Mechanically, CYTOR acts as a competitive endogenous RNA (ceRNA) to absorb miR-125a-5p, weakens the antitumor function of miR-125a-5p, and ultimately upregulates ANLN and RRM2 expressions. Taken together, this study explains the mechanism of lncRNA in the gemcitabine resistance of LUAD and formulates a theoretical framework for the in depth study of LUAD.

Association of gestational cardiovascular health with infant neurodevelopment: A prospective study in Hefei of Anhui, China.

We investigate the prospective the association of gestational cardiovascular health (CVH) with infant neurodevelopment, and whether such relation was mediated by cord blood metabolites. The data come from the prospective birth cohort study in Hefei of Anhui, China. A total of 1714 mother-infant pairs are included from March 2018 and June 2021. CVH was evaluated at 24 to 28 gestational weeks by the combination of five metrics: body mass index, blood pressure, total cholesterol, glucose, and smoking. Cord blood samples were collected at delivery for the detection of related indicators. Infant neurodevelopment at 12 months was assessed by the Ages and Stages Questionnaire Edition 3 (ASQ-3). We stratified the status of CVH into three levels, ideal, intermediate, and poor. Compared with the ideal CVH, poor CVH was associated with infant communication domain failure (RR = 2.06; 95 %CI, 1.24-3.42) and cord blood C-peptide levels (ß = 0.09; 95 %CI, 0.06-0.13) were higher. Cord blood C-peptide level with infant communication domain failure risk increased (RR = 3.43, 95 %CI: 2.11-5.58). Mediation analysis showed that cord blood C-peptide mediated 13.9 % of the effect. Key findings indicated that maternal poor CVH at 24 to 28 weeks gestation was associated with an increased risk of infant neurodevelopment at ASQ-3 failure in the communication domain, and cord blood C-peptide might mediate this association. The findings, if confirmed by replications, specific nursing cares among pregnant women with poor CVH, might have implications for the offspring neurodevelopment prevention strategies targeting.

FOXP1 and KLF2 reciprocally regulate checkpoints of stem-like to effector transition in CAR T cells.

In cancer and infections, self-renewing stem-like CD8+ T cells mediate the response of immunotherapies and replenish terminally exhausted T cells and effector-like T cells. However, the programs governing the lineage choice in chimeric antigen receptor (CAR) T cells are unclear. Here, by simultaneously profiling single-cell chromatin accessibility and transcriptome in the same CAR T cells, we identified heterogeneous chromatin states within CD8+ T cell subsets that foreshadowed transcriptional changes and were primed for regulation by distinct transcription factors. Transcription factors that controlled each CD8+ T cell subset were regulated by high numbers of enhancers and positioned as hubs of gene networks. FOXP1, a hub in the stem-like network, promoted expansion and stemness of CAR T cells and limited excessive effector differentiation. In the effector network, KLF2 enhanced effector CD8+ T cell differentiation and prevented terminal exhaustion. Thus, we identified gene networks and hub transcription factors that controlled the differentiation of stem-like CD8+ CAR T cells into effector or exhausted CD8+ CAR T cells.

Disclosing the effect of exogenous betaine on growth of Suaeda salsa (L.) Pall in the Liaohe coastal wetland, North China.

Liaohe coastal wetland has experienced severe degradation of Suaeda salsa (L.) Pall (S. salsa) in recent years. However, the impact of exogenous betaine (GB) on S. salsa growth remains unclear. Therefore, we conducted a natural simulated cultivation in soils of coastal wetland to investigate the effects of GB on S. salsa growth. The results showed that GB increased the height and weight of S. salsa, and meanwhile stimulated the synthesis of endogenous betaine and amino acids, increased soluble sugars and elevated the activity of Na+, K+-ATPase (enhancing osmotic stability). In addition, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) increased, and malondialdehyde (MDA) and H2O2 decreased correspondingly, thereby improving the antioxidant capacity. Overall, GB application significantly alleviated salt stress and effectively promoted S. salsa growth. This study first indicated the important role of GB in influencing S. salsa growth, offering potential strategies for remediation in coastal wetlands.

Microfluidic Fabrication of MicroRNA-Induced Hepatocyte-Like Cells/Human Umbilical Vein Endothelial Cells-Laden Microgels for Acute Liver Failure Treatment.

Acute liver failure (ALF) is a critical life-threatening disease that occurs due to a rapid loss in hepatocyte functions. Hepatocyte transplantation holds great potential for ALF treatment, as it rapidly supports liver biofunctions and enhances liver regeneration. However, hepatocyte transplantation is still limited by renewable and ongoing cell sources. In addition, intravenously injected hepatocytes are primarily trapped in the lungs and have limited efficacy because of the rapid clearance in vivo. Here, we designed a Y-shaped DNA nanostructure to deliver microRNA-122 (Y-miR122), which could induce the hepatic differentiation and maturation of human mesenchymal stem cells. mRNA sequencing analysis revealed that the Y-miR122 promoted important hepatic biofunctions of the induced hepatocyte-like cells including fat and lipid metabolism, drug metabolism, and liver development. To further improve hepatocyte transplantation efficiency and therapeutic effects in ALF treatment, we fabricated protective microgels for the delivery of Y-miR122-induced hepatocyte-like cells based on droplet microfluidic technology. When cocultured with human umbilical vein endothelial cells in microgels, the hepatocyte-like cells exhibited an increase in hepatocyte-associated functions, including albumin secretion and cytochrome P450 activity. Notably, upon transplantation into the ALF mouse model, the multiple cell-laden microgels effectively induced the restoration of liver function and enhanced liver regeneration. Overall, this study presents an efficient approach from the generation of hepatocyte-like cells to hepatocyte transplantation in ALF therapy.

Assessment of 2022 European LeukemiaNet risk classification system in real-world cohort from China.

BACKGROUND: The European LeukemiaNet (ELN) risk classification system for acute myeloid leukemia (AML) patients has been used worldwide. In 2022, the ELN risk classification system modified risk genes including CEBPA mutation status, myelodysplasia-related (MR) gene mutations and internal tandem duplications of FLT3 (FLT3-ITD). METHODS: We include newly diagnosed de novo AML patients at our center from January 2017 to December 2021, regardless of the further treatment received. Clinical data and date of survival were included. Survival analysis were performed using the Kaplan-Meier method, and the log-rank test was used to compare survival between different risk groups. RESULTS: We include 363 newly diagnosed de novo AML patients from 2017 to 2021 to assess the accuracy of the ELN risk classification system. Their survival results show that the ELN-2022 risk classification system is not superior to the ELN-2017 version; for patients with FLT3-ITD mutations but without FLT3 inhibitor treatment, their survival is similar to the ELN-2022 adverse risk group. The ELN-2022 risk classification system cannot accurately clarify ECOG performance status (PS) 2-4 patients, especially in the ELN-2022 favorable risk group. CONCLUSION: The ELN-2022 risk stratification system may not be appropriate for patients unable to receive intensive therapy or FLT3 inhibitor; more real-world data is needed to straify patients with worse ECOG PS and inferior intensive therapy.

Malignant proliferative ependymoma of the neck with lymph node metastasis: A case report.

BACKGROUND: Malignant proliferating trichilemmal tumor (MPTT) is an infrequent malignant neoplasm originating from cutaneous appendages, with only a handful of documented cases. This report delineates a unique instance of MPTT situated in the neck, accompanied by lymph node metastasis. A comprehensive exposition of its clinical trajectory and imaging manifestation is presented, aiming to enhance comprehension and management of this atypical ailment. CASE SUMMARY: Patient concerns: A 79-year-old male presented with a longstanding right neck mass persisting for over six decades, exhibiting recent enlargement over the past year. Diagnoses: Enhanced magnetic resonance imaging of the neck unveiled an elliptical mass on the right neck side, characterized by an ill-defined border and a heterogeneous signal pattern. The mass exhibited subdued signal intensity on T1-weighted imaging (T1WI) and a heterogeneous high signal on T2-weighted imaging (T2WI), interspersed with a lengthy T1 and T2 cystic signal motif. Close anatomical association with the submandibular gland joint was noted, and intravenous gadolinium diethylene triamine pentaacetic acid administration facilitated conspicuous enhancement. Substantial enhancement of the solid segment prompted an initial preoperative diagnosis of malignant nerve sheath tumor. However, post-surgery histopathological and immunohistochemical analysis conclusively confirmed the diagnosis as malignant hyperplastic external hair root sheath tumor. Intervention: Complete excision of the tumor was successfully executed. Outcomes: The patient experienced a favorable postoperative recovery. CONCLUSION: Malignant proliferative trichilemmal tumor external hair root sheath tumor is a cystic-solid lesion, appearing as low signal on T1WI images or high signal on T2WI with enhancement of the solid component. Suspicions of malignancy are heightened when the tumor border is indistinct, tissue planes are breached, or when linear or patchy high signals are observed in the subcutaneous tissue on T1 liver acquisition with volume acceleration enhanced images along with intermediate signal on T2WI and restricted diffusion on diffusion-weighted imaging images. Strong consideration for malignancy should arise if there are signs of compromised adjacent tissue relationships or direct invasion evident on imaging. We have incorporated the above-mentioned content into the entire manuscript.

A LIGHTFUL nanomedicine overcomes EGFR-mediated drug resistance for enhanced tyrosine-kinase-inhibitor-based hepatocellular carcinoma therapy.

Targeting the activated epidermal growth factor receptor (EGFR) via clustered regularly interspaced short palindromic repeat (CRISPR) technology is appealing to overcome the drug resistance of hepatocellular carcinoma (HCC) towards tyrosine kinase inhibitor (TKI) therapy. However, combining these two distinct drugs using traditional liposomes results in a suboptimal synergistic anti-HCC effect due to the limited CRISPR/Cas9 delivery efficiency caused by lysosomal entrapment after endocytosis. Herein, we developed a liver-targeting gene-hybridizing-TKI fusogenic liposome (LIGHTFUL) that can achieve high CRISPR/Cas9 expression to reverse the EGFR-mediated drug resistance for enhanced TKI-based HCC therapy efficiently. Coated with a galactose-modified membrane-fusogenic lipid layer, LIGHTFUL reached the targeting liver site to fuse with HCC tumor cells, directly and efficiently transporting interior CDK5- and PLK1-targeting CRISPR/Cas9 plasmids (pXG333-CPs) into the HCC cell cytoplasm and then the cell nucleus for efficient expression. Such membrane-fusion-mediated pXG333-CP delivery resulted in effective downregulation of both CDK5 and PLK1, sufficiently inactivating EGFR to improve the anti-HCC effects of the co-delivered TKI, lenvatinib. This membrane-fusion-participant codelivery strategy optimized the synergetic effect of CRISPR/Cas9 and TKI combinational therapy as indicated by the 0.35 combination index in vitro and the dramatic reduction of subcutaneous and orthotopic TKI-insensitive HCC tumor growth in mice. Therefore, the established LIGHTFUL provides a unique co-delivery platform to combine gene editing and TKI therapies for enhanced synergetic therapy.

Multimodal Tetrahedral DNA Nanoplatform for Surprisingly Rapid and Significant Treatment of Acute Liver Failure.

Acute liver failure (ALF) is a life-threatening disease associated with the rapid development of inflammatory storms, reactive oxygen species (ROS) level elevation, and hepatocyte necrosis, which results in high short-term mortality. Except for liver transplantation, no effective strategies are available for ALF therapy due to the rapid disease progression and narrow therapeutic time window. Therefore, there is an urgent demand to explore fast and effective modalities for ALF treatment. Herein, a multifunctional tetrahedral DNA nanoplatform (TDN) is constructed by incorporating the tumor necrosis factor-α siRNA (siTNF-α) through DNA hybridization and antioxidant manganese porphyrin (MnP4) via π-π stacking interaction with G-quadruplex (G4) for surprisingly rapid and significant ALF therapy. TDN-siTNF-α/-G4-MnP4 silences TNF-α of macrophages by siTNF-α and polarizes them to the anti-inflammatory M2 phenotype, providing appropriate microenvironments for hepatocyte viability. Additionally, TDN-siTNF-α/-G4-MnP4 scavenges intracellular ROS by MnP4 and TDN, protecting hepatocytes from oxidative stress-associated cell death. Furthermore, TDN itself promotes hepatocyte proliferation via modulating the cell cycle. TDN-siTNF-α/-G4-MnP4 shows almost complete liver accumulation after intravenous injection and exhibits excellent therapeutic efficacy of ALF within 2 h. The multifunctional DNA nanoformulation provides an effective strategy for rapid ALF therapy, expanding its application for innovative treatments for liver diseases. This article is protected by copyright. All rights reserved.

Novel Insights into Uptake, Translocation, and Transformation Mechanisms of 2,2',4,4'-Tetra Brominated Diphenyl Ether (BDE-47) in Wheat (Triticum aestivum L.): Implication by Compound-Specific Stable Isotope and Transcriptome Analysis.

The uptake, translocation, and transformation of 2,2',4,4'-tetra brominated diphenyl ether (BDE-47) in wheat (Triticum aestivum L.) were comprehensively investigated by hydroponic experiments using compound-specific stable isotope analysis (CSIA) and transcriptome analysis. The results indicated that BDE-47 was quickly adsorbed on epidermis of wheat roots and then absorbed in roots via water and anion channels as well as an active process dependent on energy. A small fraction of BDE-47 in roots was subjected to translocation acropetally, and an increase of δ13C values in shoots than roots implied that BDE-47 in roots had to cross at least one lipid bilayer to enter the vascular bundle via transporters. In addition, accompanied by the decreasing concentrations, δ13C values of BDE-47 showed the increasing trend with time in shoots, indicating occurrence of BDE-47 transformation. OH-PBDEs were detected as transformation products, and the hydroxyl group preferentially substituted at the ortho-positions of BDE-47. Based on transcriptome analysis, genes encoding polybrominated diphenyl ether (PBDE)-metabolizing enzymes, including cytochrome P450 enzymes, nitrate reductases, and glutathione S-transferases, were significantly upregulated after exposure to BDE-47 in shoots, further evidencing BDE-47 transformation. This study first reported the stable carbon isotope fractionation of PBDEs during translocation and transformation in plants, and application of CSIA and transcriptome analysis allowed systematically characterize the environmental behaviors of pollutants in plants.