Fatty Acid Oxidation Supports Lymph Node Metastasis of Cervical Cancer via Acetyl-CoA-Mediated Stemness.

Accumulating evidence indicates that metabolic reprogramming of cancer cells supports the energy and metabolic demands during tumor metastasis. However, the metabolic alterations underlying lymph node metastasis (LNM) of cervical cancer (CCa) have not been well recognized. In the present study, it is found that lymphatic metastatic CCa cells have reduced dependency on glucose and glycolysis but increased fatty acid oxidation (FAO). Inhibition of carnitine palmitoyl transferase 1A (CPT1A) significantly compromises palmitate-induced cell stemness. Mechanistically, FAO-derived acetyl-CoA enhances H3K27 acetylation (H3K27Ac) modification level in the promoter of stemness genes, increasing stemness and nodal metastasis in the lipid-rich nodal environment. Genetic and pharmacological loss of CPT1A function markedly suppresses the metastatic colonization of CCa cells in tumor-draining lymph nodes. Together, these findings propose an effective method of cancer therapy by targeting FAO in patients with CCa and lymph node metastasis.

Application of Acoustic Radiation Force Pulse Imaging Technology in the Evaluation of the Efficacy of Calf Intermuscular Vein Thrombosis.

BACKGROUND: The continuous advancement in ultrasound technology has given rise to Acoustic Radiation Force Impulse (ARFI) elastography, which boasts non-invasiveness, ease of operation, rapid inspection, and high accuracy. It has been successfully employed in detecting tissue hardness across various diseases. This study aims to investigate the application of acoustic radiation force pulse imaging technology in evaluating the efficacy of calf intermuscular vein thrombosis. METHODS: This study is retrospective in nature, involving a total of 120 patients diagnosed with calf intermuscular venous thrombosis (MCVT) who were admitted to our hospital. These patients were selected retrospectively as the subjects for our research. They were subsequently divided into two groups: the control group and the observation group. The control group received standard nursing care and simple pressure therapy, while the observation group underwent anticoagulant drug treatment. The shear wave elastic hardness of both groups was measured, with the recording of ultrasonic elasticity scores and the average elastic modulus value (E-mean, in kPa). Furthermore, a comparison was made between the two groups regarding thrombus disappearance time, blood flow patency, and the clinical treatment effect. RESULTS: At the 1, 3, and 6-month marks of the treatment period, the ultrasonic elasticity scores in the observation group were consistently higher compared to those in the control group. Additionally, the shear wave elastic hardness in the observation group was consistently lower than that in the control group, and these differences were found to be statistically significant (p < 0.05). The total effective rates for the control and observation groups were 83.33% and 95.00%, respectively. Notably, the clinical total effective rate in the observation group was significantly higher than that in the control group, and this difference was statistically significant (p < 0.05). The thrombus disappearance time in the observation group was significantly shorter than that in the control group, and the blood flow rate was significantly higher than in the control group, with both differences being statistically significant (p < 0.05). CONCLUSION: ARFI plays a crucial role in assessing the efficacy of MCVT by effectively revealing the hardness and location of the patient's thrombus tissue. This technology aids doctors in gaining a more precise understanding of the deep vein thrombosis condition. Notably, ARFI is characterized by high safety levels and exhibits positive effects due to its painless and non-invasive nature.

Automated machine learning for the identification of asymptomatic COVID-19 carriers based on chest CT images.

BACKGROUND: Asymptomatic COVID-19 carriers with normal chest computed tomography (CT) scans have perpetuated the ongoing pandemic of this disease. This retrospective study aimed to use automated machine learning (AutoML) to develop a prediction model based on CT characteristics for the identification of asymptomatic carriers. METHODS: Asymptomatic carriers were from Yangzhou Third People's Hospital from August 1st, 2020, to March 31st, 2021, and the control group included a healthy population from a nonepizootic area with two negative RT‒PCR results within 48 h. All CT images were preprocessed using MATLAB. Model development and validation were conducted in R with the H2O package. The models were built based on six algorithms, e.g., random forest and deep neural network (DNN), and a training set (n = 691). The models were improved by automatically adjusting hyperparameters for an internal validation set (n = 306). The performance of the obtained models was evaluated based on a dataset from Suzhou (n = 178) using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and F1 score. RESULTS: A total of 1,175 images were preprocessed with high stability. Six models were developed, and the performance of the DNN model ranked first, with an AUC value of 0.898 for the test set. The sensitivity, specificity, PPV, NPV, F1 score and accuracy of the DNN model were 0.820, 0.854, 0.849, 0.826, 0.834 and 0.837, respectively. A plot of a local interpretable model-agnostic explanation demonstrated how different variables worked in identifying asymptomatic carriers. CONCLUSIONS: Our study demonstrates that AutoML models based on CT images can be used to identify asymptomatic carriers. The most promising model for clinical implementation is the DNN-algorithm-based model.

Fabrication of Schiff-base crosslinked films modified dialdehyde starch with excellent UV-blocking and antibacterial properties for fruit preservation.

Starch-based films have received considerable attention, owing to their commendable biocompatible and biodegradable properties; however, their poor ultraviolet (UV)-blocking and antibacterial performances limit their application in fruit preservation. Herein, bio-based bifunctional benzoxazine (Bi-BOZ) compounds with different carbon chain lengths were synthesized, and the influence of chain lengths on the antibacterial effect was explored. Benzoxazine with 1,12-dodecanediamine as the amine source (BOZ-DDA) exhibited excellent antibacterial and antibiofilm activities, with minimum inhibitory concentrations of 21.7 ± 2.2 and 23.3 ± 2.6 µg/mL against Escherichia coli and Staphylococcus aureus, respectively, mainly because the electrostatic attraction and hydrophobic effect of BOZ-DDA, effectively disrupted the bacterial integrity. DS/DDA films with hydrophobic, antibacterial, and UV-resistant abilities were prepared by the Schiff-base reaction between BOZ-DDA and dialdehyde starch (DS). The interactions between the films increased with BOZ-DDA content, enhanced mechanical and barrier properties. DS/DDA films exhibited acid-responsive antibacterial activity attributed to the acid hydrolysis of Schiff bases, released of BOZ-DDA from the films, and the protonation of BOZ-DDA. DS/DDA films exhibited commendable antibacterial and anti-ultraviolet characteristics compared to commercially available films, allowing them to prevent the degradation of mangoes and grapes. As sustainable antibacterial materials, the multifunctional DS/DDA films manifest promising prospects in fruit preservation packaging applications.

Patient-derived organoids as personalized avatars and a potential immunotherapy model in cervical cancer.

Cervical cancer remains a significant health issue in developing countries. However, finding a preclinical model that accurately reproduces tumor characteristics is challenging. Therefore, we established a patient-derived organoids (PDOs) biobank containing 67 cases of heterogeneous cervical cancer that mimic the histopathological and genomic characteristics of parental tumors. The in vitro response of the organoids indicated their ability to capture the radiological heterogeneity of the patients. To model individual responses to adoptive T cell therapy (ACT), we expanded tumor-infiltrating lymphocytes (TILs) ex vivo and co-cultured them with paired organoids. The PDOs-TILs co-culture system demonstrates clear responses that correspond to established immunotherapy efficiency markers like the proportion of CTLs. This study supports the potential of the PDOs platform to guide treatment in prospective interventional trials in cervical cancer.

Shunt rate of ductus arteriosus and ductus venosus in middle and late fetuses and their application value in the evaluation of fetal growth restriction.

Objective: To explore the Shunt rate of ductus arteriosus (DA) and ductus venosus (DV) in middle and late fetuses and their application value in the evaluation of fetal growth restriction (FGR). Methods: In this retrospective observational study, we reviewed the clinical data of the patients who admitted to the Second Affiliated Hospital of Wenzhou Medical University from September 10, 2017 to November 27, 2018, and finally included 44 normal women at 28-31 weeks of pregnancy (Normal group) and 15 pregnant women with fetal growth restriction (FGR) within 28-31 weeks of gestation (FGR group). We measured blood flows of the DA (QDA), pulmonary artery (QPA), DV (QDV), and umbilical vein (QUV) and the shunt rates of the DA and DV (QDA/QPA and QDV/QUV, respectively) in all fetuses. We compared the mean variables between groups using the Normal group means as the normal reference values for analysis. Results: DA shunt rate was linearly and positively correlated with gestational age (Y=1.455X+2.787; r=0.767, P<0.01), while the DV shunt rate was linearly and negatively correlated with gestational age (Y=-2.791X+126.885; r=0.761, P<0.01). The DA shunt rates (QDA/QPA) of fetuses in the normal were higher than those in the FGR groups, but the differences between the two groups were not statistically significant (P > 0.05). The DV shunt rates (QDV/QUV) of fetuses in the normal were significantly lower than those in the FGR groups (P < 0.05). The DV shunt rates in the FGR group were significantly higher than those in the normal group with differences being statistically significant at 30-30+6 and 31-31+6 gestational weeks (P < 0.05) The receiver operating characteristic curve (ROC curve) showed that the higher the shunt rate, the worse the birth outcome of a fetus with FGR. Conclusions: The DV shunt rate in middle- and late-stage fetuses can predict the fetal birth outcome, and the higher the shunt ratio, the worse the birth outcome of FGR fetuses.

Identification of Asymptomatic COVID-19 Patients on Chest CT Images Using Transformer-Based or Convolutional Neural Network-Based Deep Learning Models.

Novel coronavirus disease 2019 (COVID-19) has rapidly spread throughout the world; however, it is difficult for clinicians to make early diagnoses. This study is to evaluate the feasibility of using deep learning (DL) models to identify asymptomatic COVID-19 patients based on chest CT images. In this retrospective study, six DL models (Xception, NASNet, ResNet, EfficientNet, ViT, and Swin), based on convolutional neural networks (CNNs) or transformer architectures, were trained to identify asymptomatic patients with COVID-19 on chest CT images. Data from Yangzhou were randomly split into a training set (n = 2140) and an internal-validation set (n = 360). Data from Suzhou was the external-test set (n = 200). Model performance was assessed by the metrics accuracy, recall, and specificity and was compared with the assessments of two radiologists. A total of 2700 chest CT images were collected in this study. In the validation dataset, the Swin model achieved the highest accuracy of 0.994, followed by the EfficientNet model (0.954). The recall and the precision of the Swin model were 0.989 and 1.000, respectively. In the test dataset, the Swin model was still the best and achieved the highest accuracy (0.980). All the DL models performed remarkably better than the two experts. Last, the time on the test set diagnosis spent by two experts-42 min, 17 s (junior); and 29 min, 43 s (senior)-was significantly higher than those of the DL models (all below 2 min). This study evaluated the feasibility of multiple DL models in distinguishing asymptomatic patients with COVID-19 from healthy subjects on chest CT images. It found that a transformer-based model, the Swin model, performed best.

Insights on the biological functions and diverse regulation of RNA-binding protein 39 and their implication in human diseases.

RNA-binding protein 39 (RBM39) involves in pre-mRNA splicing and transcriptional regulation. RBM39 is dysregulated in many cancers and its upregulation enhances cancer cell proliferation. Recently, it has been discovered that aryl sulfonamides act as molecular glues to recruit RBM39 to the CRL4DCAF15 E3 ubiquitin ligase complex for its ubiquitination and proteasomal degradation. Therefore, various studies have focused on the degradation of RBM39 by aryl sulfonamides in the aim of finding new cancer therapeutics. These discoveries also attracted focus for thorough study on the biological functions of RBM39. RBM39 was found to regulate the splicing and transcription of genes mainly involved in pre-mRNA splicing, cell cycle regulation, DNA damage response, and metabolism, but the understanding of these regulations is still in its infancy. This article reviews the advances of the current literature and discusses the remaining key issues on the biological function and dynamic regulation of RBM39 at the post-translational level.

Mechanistic Insights into Membrane Protein Clustering Revealed by Visualizing EGFR Secretion.

Most plasmalemmal proteins are organized into clusters to modulate various cellular functions. However, the machineries that regulate protein clustering remain largely unclear. Here, with EGFR as an example, we directly and in detail visualized the entire process of EGFR from synthesis to secretion onto the plasma membrane (PM) using a high-speed, high-resolution spinning-disk confocal microscope. First, colocalization imaging revealed that EGFR secretory vesicles underwent transport from the ER to the Golgi to the PM, eventually forming different distribution forms on the apical and basal membranes; that is, most EGFR formed larger clusters on the apical membrane than the basal membrane. A dynamic tracking image and further siRNA interference experiment confirmed that fusion of secretory vesicles with the plasma membrane led to EGFR clusters, and we showed that EGFR PM clustering may be intimately related to EGFR signaling and cell proliferation. Finally, we found that the size and origin of the secretory vesicles themselves may determine the difference in the distribution patterns of EGFR on the PM. More importantly, we showed that actin influenced the EGFR distribution by controlling the fusion of secretory vesicles with the PM. Collectively, a comprehensive understanding of the EGFR secretion process helps us to unravel the EGFR clustering process and elucidate the key factors determining the differences in the spatial distribution of EGFR PM, highlighting the correlation between EGFR secretion and its PM distribution pattern.

High-density thermal sensitivity of the hand under different thermal states and stimulus intensities.

Understanding how the human body senses small-scale heating and cooling stimuli can help researchers evaluate thermal comfort effects and health risks of thermal stimulus combinations under complex thermal exposure. Two experiments measured high-density thermal sensitivity on the hand to investigate whether the initial thermal states and stimulus intensities affect thermal sensitivity. After pilot tests, a 23°C cold-water bath and a 41°C hot-water bath were applied to create initial states deviating from thermal neutrality. The whole hand and part of the wrist with all test spots were immersed for 1 min and dried by a towel. Results showed that cold sensitivity and warmth sensitivity have a linear relationship with each other, but 16 of 20 subjects (80%) were more sensitive to cooling than to heating. The 1-min water-bath treatment significantly reduced hand thermal sensitivity. Compared with a thermally neutral state, a cold-water bath and hot-water bath reduced cold sensitivity by 22% and 61%, respectively, and reduced warmth sensitivity by 47% and 51%, respectively. Under a thermally neutral state, the perceptible thresholds for cooling and heating stimuli were -1.3°C and +1.8°C, respectively. Comfortable stimulating temperature ranges were 24°C-30°C for cooling and 34°C-39°C for heating. Thermal sensitivity differences among stimulus intensities were small, but differences among test spots and subjects were significant.

An Analysis on the Factors for Cervical Insufficiency Causing Adverse Emotions Among Pregnant Women at Different Gestation Phases.

Background: To analyze the anxiety, depression, and related factors among pregnant women with cervical insufficiency, so as to provide a reference for clinical psychological intervention as an adjuvant therapy. Methods: A total of 101 cases in China with cervical insufficiency were included in the observation group by a convenience sampling method, and 114 normal healthy women of childbearing age were selected as the control group. Participants were investigated and observed for anxiety and depression by SAS and SDS, respectively, to analyze the emotional state and influencing factors of the patients with cervical insufficiency. Stratified by the first, second and third trimesters, our study used whether depressive or not and whether anxiety or not as the dichotomous variables. A multivariate Logistic regression was adopted to analyze the influencing factors. Relevant influencing factors were screened out by the forward stepwise method in combination with professional knowledge and the number of variables. Results: There were statistical significant differences in SAS and SDS between observation group and control group and the incidence rate of anxiety and depression was higher in pregnant women with CI. Multivariate Logistic regression demonstrated that history of abnormal pregnancy was the main influencing factor for anxiety and depression in the early and middle gestation phases, and cervical insufficiency was the factor influencing the anxiety in early gestation and both anxiety and depression in the late gestation phase. Conclusion: Cervical insufficiency may have a negative impact on the emotions of pregnant women. Individualized and targeted mental care should be added into clinic work to prevent negative outcomes.

Ternary Electrical Memory Devices Based on Polycarbazole: SnO2 Nanoparticles Composite Material.

In this paper, a D-A polymer (PIB) containing carbazole as the donor group in the main chain and benzimidazole benzisoindolinone as the acceptor group was synthesized by Suzuki reaction. The Suzuki reaction, also known as the Suzuki coupling reaction, is a relatively new organic coupling reaction in which aryl or alkenyl boronic acids or boronic acid esters react with chlorine, bromine, iodoaromatic hydrocarbons or alkenes under the catalysis of zerovalent palladium complexes cross-coupling. A series of devices were fabricated by a spin-coating approach, and the devices all exhibited ternary resistance switching storage behavior. Among them, the composite device with the mass fraction of SnO2 NPs of 5 wt% has the best storage performance, with a threshold voltage of -0.4 V and a switching current ratio of 1:101.5:104.5. At the same time, the current of the device remained stable after a 3-h test. Furthermore, after 103 cycles, the current has no obvious attenuation. The device has good stability and continuity. Moreover, the conduction mechanism is further revealed. Inorganic nanoparticle composite devices have splendid memory performances and exhibit underlying application significance in storing data.

In situ construction of flower-like nanostructured calcium silicate bioceramics for enhancing bone regeneration mediated via FAK/p38 signaling pathway.

BACKGROUND: The repair of tissue defects has attracted considerable attention and remained a substantial challenge. Calcium silicate (CaSiO3, CS) bioceramics have attracted the interest of researchers due to their excellent biodegradability. Recent studies have demonstrated that nanoscale-modified bioactive materials with favorable biodegradability could promote bone tissue regeneration, providing an alternative approach for the repair of bone defects. However, the direct construction of biodegradable nanostructures in situ on CS bioceramics was still difficult. RESULTS: In this study, flower-like nanostructures were flexibly prepared in situ on biodegradable CS bioceramics via hydrothermal treatment. The flower-like nanostructure surfaces exhibited better hydrophilicity and more significantly stimulated cell adhesion, alkaline phosphatase (ALP) activity, and osteogenic differentiation. Furthermore, the CS bioceramics with flower-like nanostructures effectively promoted bone regeneration and were gradually replaced with newly formed bone due to the favorable biodegradability of these CS bioceramics. Importantly, we revealed an osteogenesis-related mechanism by which the FAK/p38 signaling pathway could be involved in the regulation of bone mesenchymal stem cell (BMSC) osteogenesis by the flower-like nanostructure surfaces. CONCLUSIONS: Flower-like nanostructure surfaces on CS bioceramics exerted a strong effect on promoting bone repair and regeneration, suggesting their excellent potential as bone implant candidates for improving bone regeneration.

Ternary Flash Memory with a Carbazole-Based Conjugated Copolymer: WS2 Composites as Active Layers.

For nonvolatile memory devices, the design and synthesis of their substrate materials are very important. Due to the versatility and large-area fabrication of the low-temperature spin coating process, organic/inorganic nanomaterials as active layers of memory devices have been deeply studied. Inorganic nanoparticles can engage in interactions with polymers via external voltage. WS2 NPs have a large specific surface area and good conductivity. They can be used as the charge trap center in the active layer, which is conducive to the charge transfer in the active layer. Poly[2,7-9-(9-heptadecanyl)-9H-carbazole-co-benzo[4,5] imidazole[2,1-α] isoindol-11-one] (PIIO) was synthesized via the Suzuki coupling reaction. ITO/PIIO/Al and ITO/PIIO:WS2 NP/Al devices were prepared by the spin coating method and vacuum evaporation technology. All devices showed tristable switching behavior. The influence of the WS2 mass fraction on memory performance was studied. The device composite with 6 wt % WS2 NPs showed the best storage features. The OFF/ON1/ON2 current ratio was 1: 1.11 × 101: 2.03 × 104, and the threshold voltage Vth1/Vth2 was -0.60 V/-1.05 V. The device is steady for 12,000 s in three states-high-resistance state (HRS), intermediate state (IRS), and low-resistance state (LRS). After reading 3500 times, the switch-state current displayed no obvious attenuation. This work shows that the polymer and its composites have broad prospects in next-generation nonvolatile storage.

Downregulation of LNMAS orchestrates partial EMT and immune escape from macrophage phagocytosis to promote lymph node metastasis of cervical cancer.

Epithelial-mesenchymal transition (EMT) is an essential step to drive the metastatic cascade to lymph nodes (LNs) in cervical cancer cells. However, few of them metastasize successfully partially due to increased susceptibility to immunosurveillance conferred by EMT. The precise mechanisms of cancer cells orchestrate EMT and immune evasion remain largely unexplored. In this study, we identified a lncRNA termed lymph node metastasis associated suppressor (LNMAS), which was downregulated in LN-positive cervical cancer patients and correlated with LN metastasis and prognosis. Functionally, LNMAS suppressed cervical cancer cells metastasis in vitro and in vivo. Mechanistically, LNMAS exerts its metastasis suppressive activity by competitively interacting with HMGB1 and abrogating the chromatin accessibility of TWIST1 and STC1, inhibiting TWIST1-mediated partial EMT and STC1-dependent immune escape from macrophage phagocytosis. We further demonstrated that the CpG sites in the promoter region of LNMAS was hypermethylated and contributed to the downregulation of LNMAS. Taken together, our results reveal the essential role of LNMAS in the LN metastasis of cervical cancer and provide mechanistic insights into the regulation of LNMAS in EMT and immune evasion.

Circular RNA hsa_circ_0043280 inhibits cervical cancer tumor growth and metastasis via miR-203a-3p/PAQR3 axis.

Circular RNAs (circRNAs) are known to act as key regulators in a variety of malignancies. However, the role of circRNAs in cervical cancer (CCa) remains largely unknown. Herein, we demonstrated that a circRNA derived from the TADA2A gene (hsa_circ_0043280) was significantly downregulated in CCa and that this reduction in expression was correlated with a poor prognosis. Furthermore, our results demonstrated that hsa_circ_0043280 functions as a tumor suppressor to inhibit tumor growth and metastasis in CCa. Mechanistically, hsa_circ_0043280 competitively sponges miR-203a-3p and prevents miR-203a-3p from reducing the levels of PAQR3. Collectively, our results demonstrate that hsa_circ_0043280 plays a pivotal role in the development and metastasis of CCa, thus suggesting that hsa_circ_0043280 has significant potential as a prognostic biomarker and a therapeutic target for CCa.

TAB2 Promotes the Stemness and Biological Functions of Cervical Squamous Cell Carcinoma Cells.

Cancer stem cells are a key population participating in the promotion of the cervical cancer progression through interacting with cancer cells. Existing studies have preliminary revealed that cervical cancer stem cells contribute to tumor recurrence and chemotherapy resistance. However, the specific mechanisms involved in regulating cell functions remain largely unknown. Here, we analyzed published data from public databases and our global transcriptome data, thus identifying cancer-related signaling pathways and molecules. According to our findings, upregulated TAB2 was correlated to stem cell-like properties of cervical cancer. Immunohistochemistry staining of TAB2 in normal and cervical cancer tissues was performed. The cell function experiments demonstrated that knockdown of TAB2 reduced the stemness of cervical cancer cells and, importantly, prevented cervical cancer progression. Collectively, the therapeutic scheme targeting TAB2 may provide an option for overcoming tumor relapse and chemoresistance of cervical cancer via obstructing stemness maintenance.

The Impact of DNA Methylation Dynamics on the Mutation Rate During Human Germline Development.

DNA methylation is a dynamic epigenetic modification found in most eukaryotic genomes. It is known to lead to a high CpG to TpG mutation rate. However, the relationship between the methylation dynamics in germline development and the germline mutation rate remains unexplored. In this study, we used whole genome bisulfite sequencing (WGBS) data of cells at 13 stages of human germline development and rare variants from the 1000 Genome Project as proxies for germline mutations to investigate the correlation between dynamic methylation levels and germline mutation rates at different scales. At the single-site level, we found a significant correlation between methylation and the germline point mutation rate at CpG sites during germline developmental stages. Then we explored the mutability of methylation dynamics in all stages. Our results also showed a broad correlation between the regional methylation level and the rate of C > T mutation at CpG sites in all genomic regions, especially in intronic regions; a similar link was also seen at all chromosomal levels. Our findings indicate that the dynamic DNA methylome during human germline development has a broader mutational impact than is commonly assumed.

Suicide gene-mediated ablation of tumor-initiating mouse pluripotent stem cells.

Pluripotent stem cells, including embryonic stem (ES) and induced pluripotent stem (iPS) cells, serve as unlimited resources for cell replacement therapy and tissue engineering because such cells are capable of extensive proliferation in vitro and can give rise to lineages that represent any of the three embryonic germ layers. However, in the context of the in vivo behavior of cell transplants, key challenges need to be addressed and essential strategies should be developed before stem cells can be used in clinical practice. In the present study, we modified mouse ES/iPS cells to contain a suicide gene, deltaTK or CodA, under the transcriptional control of the EF1α or Nanog promoter. The suicide gene was introduced via lentivirus transduction without interfering with their self-renewal and pluripotency characteristics. We found that EF1α promoter-controlled deltaTK/CodA expression efficiently eliminated pluripotent stem cells and their derivatives both in vitro and in vivo. When the suicide gene was under the control of the Nanog promoter, tumor-initiating undifferentiated pluripotent stem cells were selectively ablated in vitro after prodrug treatment. These results indicate that modification of pluripotent stem cells with a suicide gene prior to transplantation offers a safe manner by which wayward stem cells, and their progeny, can be controlled in vivo. Our approach will render the clinical application of human pluripotent stem cells increasingly possible.