Dual-tracer PET/CT in the management of hepatocellular carcinoma.

Background & Aims: Combined 18F-fluorodeoxyglucose (FDG) and 11C-acetate (dual-tracer) positron-emission tomography/computed tomography (PET/CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels. Methods: We retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET/CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET/CT in diagnosing HCC were evaluated. A multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed. Results: Dual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n = 273, κ = 0.822; 95% CI 0.803-0.864). Conclusions: Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP. Impact and implications: Compared to CT or MRI, dual-tracer positron-emission tomography/computed tomography (PET/CT) led to upstaging in 12% of patients with hepatocellular carcinoma (HCC) undergoing staging, resulting in treatment modification in 8% of cases and a cost saving of US$495 per patient. It also accurately detected HCC in high-risk cases where CT or MRI were equivocal or normal. Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

The Impact of Reward Object on Object-Based Attention.

Reward has been shown to influence selective attention, yet previous research has primarily focused on rewards associated with specific locations or features, with limited investigation into the impact of a reward object on object-based attention (OBA). Therefore, it remains unclear whether objects previously associated with rewards affect OBA. To address this issue, we conducted two experiments using a paradigm that combined a reward training phase with a modified two-rectangle paradigm. The results indicate that a reward object modulates both space-based attention (SBA) and OBA. When cues appear on a reward object, the effects of both SBA and OBA are amplified compared to when cues appear on a no-reward object. This finding supports the value-driven attentional capture (VDAC) theory, which suggests that a reward object gain enhanced saliency to capture attention, thereby providing a theoretical support for the treatment of conditions such as drug addiction.

Mapping putative enhancers in mouse oocytes and early embryos reveals TCF3/12 as key folliculogenesis regulators.

Dynamic epigenomic reprogramming occurs during mammalian oocyte maturation and early development. However, the underlying transcription circuitry remains poorly characterized. By mapping cis-regulatory elements using H3K27ac, we identified putative enhancers in mouse oocytes and early embryos distinct from those in adult tissues, enabling global transitions of regulatory landscapes around fertilization and implantation. Gene deserts harbour prevalent putative enhancers in fully grown oocytes linked to oocyte-specific genes and repeat activation. Embryo-specific enhancers are primed before zygotic genome activation and are restricted by oocyte-inherited H3K27me3. Putative enhancers in oocytes often manifest H3K4me3, bidirectional transcription, Pol II binding and can drive transcription in STARR-seq and a reporter assay. Finally, motif analysis of these elements identified crucial regulators of oogenesis, TCF3 and TCF12, the deficiency of which impairs activation of key oocyte genes and folliculogenesis. These data reveal distinctive regulatory landscapes and their interacting transcription factors that underpin the development of mammalian oocytes and early embryos.

Gratitude and depressive symptoms in Chinese nurses: From a self-determination theory perspective.

BACKGROUND: A common psychological problem among nurses is depression, potentially affecting their well-being and job performance. It is vital to explore how to alleviate nurses' depressive symptoms. AIM: The current research explored the mediating impact of basic psychological needs satisfaction on the link of gratitude with depressive symptoms. METHODS: The nurses in this study were from mainland China. A total of 724 subjects completed an online questionnaire, which included measures of depressive symptoms, basic psychological needs satisfaction and gratitude. RESULTS: Our research found that gratitude was negatively linked to depressive symptoms. Furthermore, basic psychological needs satisfaction had a partial mediation effect on the link of gratitude with depressive symptoms after controlling for five demographic variables. These results suggest that gratitude may influence depressive symptoms via basic psychological needs satisfaction. LINKING EVIDENCE TO ACTION: Our study found that basic psychological need satisfaction partially mediates the gratitude-depression relationship in nurses. The result means that hospital administrators and nurse leaders should design gratitude interventions to alleviate nurses' depressive symptoms. They also help nurses decrease depressive symptoms by creating an environment that meets their basic psychological needs.

Survival Outcome Analysis of Stereotactic Body Radiotherapy and Immunotherapy (SBRT-IO) versus SBRT-Alone in Unresectable Hepatocellular Carcinoma.

Introduction: While combination of stereotactic body radiotherapy (SBRT) and immunotherapy are promising, their efficacy and safety have not been compared with SBRT-alone in patients with unresectable hepatocellular carcinoma (HCC). Methods: This retrospective study included 100 patients with nonmetastatic, unresectable HCC in two hospitals. Eligible patients had tumor nodules ≤3 and Child-Pugh liver function score of A5 to B7. Seventy patients received SBRT-alone, and 30 patients underwent combined SBRT and immunotherapy (SBRT-IO). Overall survival (OS), time to progression (TTP), overall response rate (ORR), and toxicity were analyzed. We adjusted for the potential confounding factors using propensity score matching. Results: The median tumor size was 7.3 cm (range, 2.6-18 cm). Twenty-five (25%) of patients had vascular invasion. Before propensity score matching, the 1-year and 3-year OS rate was 89.9% and 59.8% in the SBRT-IO group and 75.7% and 42.3% in SBRT-alone group (p = 0.039). After propensity score matching (1:2), 25 and 50 patients were selected from the SBRT-IO and SBRT-alone group. The 1-year and 3-year OS was 92.0% and 63.9% in the SBRT-IO group versus 74.0% and 43.3% in the SBRT-alone group (p = 0.034). The 1-year and 3-year TTP was better in SBRT-IO group (1-year: 68.9% vs. 58.9% and 3-year: 61.3% vs. 32.5%, p = 0.057). The ORR of 88% (complete response [CR]: 56%, partial response [PR]: 22%) in SBRT-IO arm was significantly better than 50% (CR: 20%, PR: 30%) in the SBRT-alone arm (p = 0.006). Three patients (12%) developed ≥grade 3 immune-related treatment adverse events (n = 2 hepatitis, n = 1 dermatitis) leading to permanent treatment discontinuation. Conclusion: Adding immunotherapy to SBRT resulted in better survival with manageable toxicities. Prospective randomized trial is warranted.

Addressing challenges in low-income and middle-income countries through novel radiotherapy research opportunities.

Although radiotherapy continues to evolve as a mainstay of the oncological armamentarium, research and innovation in radiotherapy in low-income and middle-income countries (LMICs) faces challenges. This third Series paper examines the current state of LMIC radiotherapy research and provides new data from a 2022 survey undertaken by the International Atomic Energy Agency and new data on funding. In the context of LMIC-related challenges and impediments, we explore several developments and advances-such as deep phenotyping, real-time targeting, and artificial intelligence-to flag specific opportunities with applicability and relevance for resource-constrained settings. Given the pressing nature of cancer in LMICs, we also highlight some best practices and address the broader need to develop the research workforce of the future. This Series paper thereby serves as a resource for radiation professionals.

Antidote or poison: The relationship between "lying flat" tendency and mental health.

Although "lying flat" has become a new youth subculture phenomenon, it is unclear whether "lying flat" is an antidote or a poison for the youth's mental health. Here, we explored the effect of "lying flat" tendency on mental health using the cross-sectional (Study 1a) and longitudinal designs (Study 1b) as well as the intervention design (Study 2). In Study 1a, we found that the youth's "lying flat" tendency was negatively correlated with their mental health. Importantly, cross-lagged analyses (Study 1b) found that "lying flat" tendency negatively predicted mental health 1 month later, suggesting the temporal directionality between "lying flat" tendency and mental health. In Study 2, we sought to examine whether a longitudinal video intervention could promote the youth's mental health by reducing "lying flat" tendency. The results showed that the eight-day inspirational video intervention significantly reduced the youth's "lying flat" tendency and promoted their mental health. Importantly, "lying flat" tendency mediated the relationship between the inspirational video intervention and mental health. Our study is the first to demonstrate the negatively predictive effect of the "lying flat" tendency on the youth's mental health and provides an economical, convenient, and effective intervention aimed at reducing the "lying flat" tendency to promote the youth's mental health.

Interpretable deep learning insights: Unveiling the role of 1 Gy volume on lymphopenia after radiotherapy in breast cancer.

BACKGROUND: Lymphopenia is known for its significance on poor survivals in breast cancer patients. Considering full dosimetric data, this study aimed to develop and validate predictive models for lymphopenia after radiotherapy (RT) in breast cancer. MATERIAL AND METHODS: Patients with breast cancer treated with adjuvant RT were eligible in this multicenter study. The study endpoint was lympopenia, defined as the reduction in absolute lymphocytes and graded lymphopenia after RT. The dose-volume histogram (DVH) data of related critical structures and clinical factors were taken into account for the development of dense neural network (DNN) predictive models. The developed DNN models were validated using external patient cohorts. RESULTS: A total of 918 consecutive patients with invasive breast cancer enrolled. The training, testing, and external validating datasets consisted of 589, 203, and 126 patients, respectively. Treatment volumes at nearly all dose levels of the DVH were significant predictors for lymphopenia following RT, including volumes at very low-dose 1 Gy (V1) of organs at risk (OARs) including lung, heart and body, especially ipsilateral-lung V1. A final DNN model, combining full DVH dosimetric parameters of OARs and three key clinical factors, achieved a predictive accuracy of 75 % or higher. CONCLUSION: This study demonstrated and externally validated the significance of full dosimetric data, particularly the volume of low dose at as low as 1 Gy of critical structures on lymphopenia after radiation in patients with breast cancer. The significance of V1 deserves special attention, as modern VMAT RT technology often has a relatively high value of this parameter. Further study is warranted for RT plan optimization.

Male reproductive function before and after the adjustment of the COVID-19 prevention policy: a multicenter study in China.

At the end of 2022, the adjustment of the coronavirus disease 2019 (COVID-19) pandemic control policy in China resulted in a large-scale increase in public infection. To compare the fertility parameters of male patients before and after the adjustments of the COVID-19 pandemic control policy in China, we collected data on patients' medical histories and laboratory examinations on their first visits between June 2022 and March 2023 in five different hospitals. Data were divided into five groups according to the timeline of the policy adjustment. The data we collected from male patients included semen quality and serum reproductive hormone levels, and intergroup comparisons were made using the Mann-Whitney U and Chi-square tests. In total, 16 784 cases underwent regular semen analysis, 11 180 had sperm morphology assessments, and 7200 had reproductive hormone analyses. The data showed declining trends in semen volume, sperm motility, and the progressive sperm motility rate after the policy adjustment. Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate. Sperm morphology analysis showed increased neck and tail abnormalities after the policy adjustment. No significant change in hormone levels was observed. Following the adjustment of the COVID-19 prevention policy in China, a decline in sperm motility and morphology was observed. This trend may gradually recover over 2 months. After the policy adjustment, reproductive hormone levels were relatively stable throughout, except for an increase in luteinizing hormone (LH). These changes in semen parameters suggest that the policy adjustment had a short- to medium-term impact on male reproductive function.

Clinical factors and major pathological response after neoadjuvant chemoimmunotherapy in potentially resectable lung squamous cell carcinoma.

Objective: Major pathological response (MPR) helps evaluate the prognosis of patients with lung squamous cell carcinoma (LUSC). However, the clinical factors that affect the achievement of MPR after neoadjuvant chemoimmunotherapy (NCIO) in patients with LUSC remain unclear. This study aimed to explore the clinical factors affecting the MPR after NCIO in patients with potentially resectable LUSC. Methods: This retrospective study included patients with stage IIB-IIIC LUSC who underwent surgical resection after receiving NCIO at a center between March 2020 and November 2022. In addition to the postoperative pathological remission rate, sex, age, body mass index (BMI), smoking history, TNM stage, hematological and imaging test results, and other indicators were examined before NCIO. According to the pathological response rate of the surgically removed tumor tissue, the patients were split into MPR and non-MPR groups. Results: In total, 91 LUSC patients who met the study's eligibility criteria were enrolled: 32 (35%) patients in the non-MPR group and 59 (65%) in the MPR group, which included 43 cases of pathological complete remission (pCR). Pre-treatment lymphocyte level (LY) (odds ratio [OR] =5.997), tumor burden (OR=0.958), N classification (OR=15.915), radiographic response (OR=11.590), pulmonary atelectasis (OR=5.413), and PD-L1 expression (OR=1.028) were independently associated with MPR (all P < 0.05). Based on these six independent predictors, we developed a nomogram model of prediction having an area under the curve (AUC) of 0.914 that is simple to apply clinically to predict the MPR. The MPR group showed greater disease-free survival (DFS) than the non-MPR group, according to the survival analysis (P < 0.001). Conclusion: The MPR rate of NCIO for potentially resectable LUSC was 65%. LY, tumor burden, N classification, radiographic response, pulmonary atelectasis, and PD-L1 expression in patients with LUSC before NCIO were the independent and ideal predictors of MPR. The developed nomogram demonstrated a good degree of accuracy and resilience in predicting the MPR following NCIO, indicating that it is a useful tool for assuring customized therapy for patients with possibly resectable LUSC.

Impact of relative and absolute values on orienting attention in time.

Reward has been known to render the reward-associated stimulus more salient to block effective attentional orienting in space. However, whether and how reward influences goal-directed attention in time remains unclear. Here, we used a modified attentional cueing paradigm to explore the effect of reward on temporal attention, in which the valid targets were given a low monetary reward and invalid targets were given a high monetary reward. The results showed that the temporal cue validity effect was significantly smaller when the competitive reward structure was employed (Experiment 1), and we ruled out the possibility that the results were due to the practice effect (Experiment 2a) or a reward-promoting effect (Experiment 2b). When further strengthening the intensity of the reward from 1:10 to 1:100 (Experiment 3), we found a similar pattern of results to those in Experiment 1. These results suggest that reward information which was based on relative instead of absolute values can weaken, but not reverse, the orienting attention in time.

Associations between emotional maltreatment, depression and self-harm among Chinese adolescents: A three-wave longitudinal mediation model.

BACKGROUND: Self-harm seriously endangers adolescents' physical and mental health. However, the longitudinal mechanism of self-harm is not yet clear. OBJECTIVE: This study explored the inconsistent relationships between two types of emotional maltreatment and self-harm across three waves, regarding depression as a potential mediator and gender as a moderator of these associations. PARTICIPANTS AND SETTING: A sample of 588 Chinese adolescents (Mage at T1 = 12.79 years) in a middle school completed the assessment of demographic information, emotional maltreatment, depression and self-harm within one year. METHODS: Path analysis models were created to estimate the relationship of emotional maltreatment with self-harm and the mediating effect of depression. A multi-group analysis was applied to investigate the moderating effect of gender. RESULTS: There existed positive associations between emotional abuse at T1 and self-harm at T2 and T3 (ß = 0.12, SE = 0.05, p = 0.006; ß = 0.09, SE = 0.05, p = 0.054), and the mediating effect of emotional abuse at T1 on self-harm at T3 via depression at T2 was significant (Indirect effect = 0.05, SE = 0.02, 95 % CI [0.02, 0.08]). Multi-group analysis of gender revealed no significant differences in the cross-lagged pathways, but there were stronger links for girls than boys among self-harm at T1, T2, and T3 (p < 0.001). CONCLUSIONS: Emotional abuse but not emotional neglect could significantly predict self-harm. Furthermore, depression played a mediating role in the longitudinal relationship between emotional abuse and self-harm. Girls who had high levels of self-harm at a previous time point were more inclined than boys to harm themselves at a subsequent time point. These findings provide a different perspective to develop effective prevention and intervention measures.

Dissociable neural correlates of trait and ability emotional intelligence: a resting-state fMRI study.

Emotional intelligence (EI) is one's ability to monitor one's own and other's emotions and the use of emotional information to enhance thought and action. Previous behavioral studies have shown that EI is separable into trait EI and ability EI, which are known to have distinct characteristics at the behavioral level. A relevant and unanswered question is whether both forms of EI have a dissociable neural basis. Previous studies have individually explored the neural underpinnings of trait EI and ability EI, but there has been no direct comparison of the neural mechanisms underlying these two types of emotional intelligence. The present study addresses this question by using resting-state fMRI to examine the correlational pattern between the regional amplitude of low-frequency fluctuations (ALFF) of the brain and individuals' trait EI and ability EI scores. We found that trait EI scores were positively correlated with the ALFF in the bilateral superior temporal gyrus, and negatively correlated with the ALFF in the ventral medial prefrontal cortex. In contrast, ability EI scores were positively correlated with the ALFF in the insula. Taken together, these results provide preliminary evidence of dissociable neural substrates between trait EI and ability EI.

A TRIZ Approach for Designing a Smart Lighting and Control System for Classrooms Based on Counter Application with Dual PIR Sensors.

Electrical energy is often wasted through human negligence when people do not switch off electrical appliances such as lighting after leaving a place. Such a scenario often happens in a classroom when the last person leaves the class and forgets to switch off the electrical appliances. Such wastage may not be able to be afforded by schools that are limited financially. Therefore, this research proposed a simple and cost-effective system that can analyze whether there is or is not a human presence in the classroom by applying a counter to count the total number of people entering and leaving the classroom based on the sensing signals of a set of dual PIR sensors only and then correlating this to automatically turn on or off the electrical appliances mentioned. The total number of people identified in the classroom is also displayed on an LCD screen. A TRIZ approach is used to support the ideation of the system. The system can switch on several electrical output loads simultaneously when the presence of people is detected and switch them off when there are no people in the classroom. The proposed system can be expanded to be used in homes, offices, and buildings to prevent the high cost of electricity consumption caused by the negligence of people. This enables smarter control of electricity consumption.

How does gratitude relate to nurses' job satisfaction? The mediating role of resilience and stress.

BACKGROUND: Nurse job satisfaction is a critical area of study with far-reaching implications for healthcare organizations, patient care, and the retention of nursing staff. AIMS: This study aimed to investigate the association of gratitude with job satisfaction among Chinese nurses and examine the potential mediating roles of resilience and stress in this relationship. METHODS: Two separate studies were conducted to examine our research hypotheses. In Study 1, a total of 460 nurses completed the questionnaire related to gratitude, resilience, stress, and job satisfaction. A validation study was conducted in Study 2, which consisted of 709 nurses who also completed the same measures of gratitude, resilience, and stress to ensure the repeatability of the Study 1 results. Furthermore, a different scale was used to measure nurses' job satisfaction. RESULTS: The two studies consistently found that both resilience and stress mediated gratitude-job satisfaction independently among Chinese nurses. Furthermore, resilience was found to be a significantly stronger mediator than stress in the association of gratitude with job satisfaction. Finally, we found that gratitude predicted nurses' job satisfaction via the serial mediating effects of resilience and stress. CONCLUSION: These findings highlight the complex interplay between gratitude, resilience, stress, and job satisfaction by demonstrating that resilience and stress act as parallel and sequential mediators between nurses' gratitude and job satisfaction. The healthcare sector can improve nurses' job satisfaction by increasing gratitude, building resilience, and reducing feelings of stress. LINKING EVIDENCE TO ACTION: Nurse managers have the potential to enhance job satisfaction among nurses by implementing measures that increase gratitude, build resilience, and reduce stress levels.

Strength Use and Well-Being at Work among Teachers: The Mediating Role of Basic Need Satisfaction.

Teachers' well-being at work is an important indicator of their mental health. Strengths use has been identified as a significant predictor of enhanced well-being at work. However, there is a scarcity of studies that have examined the connection between teachers' strengths use and well-being at work; thus, its underlying psychological mechanism is unclear. Therefore, this study aimed to explore the association between teachers' strengths and well-being at work together with the mediating role of basic need satisfaction. A total of 374 university teachers completed a series of questionnaires on strengths use, basic need satisfaction, hedonic well-being, and eudaimonic well-being. The results showed that there were positive correlations between strength use and both types of well-being at work. Moreover, basic need satisfaction mediated the association between strength use and two types of well-being at work. The findings suggest that institutions should prioritize enhancing teachers' ability to utilize their strengths and foster an environment conducive to such practices, thereby improving their workplace well-being.

Longitudinal linkages between strength use and depressive symptoms in Chinese nurses: A two wave, cross-lagged study.

Nurses are at increased risk for developing depressive symptoms. While previous research has suggested that strength use may be inversely related to these symptoms, the longitudinal impact of strength use on nurses' depressive symptoms remains under-explored. This study sought to examine the longitudinal relationship between strength use and depressive symptoms among Chinese nurses. Using a two-wave cross-lagged design from 2020 to 2023, 321 nurses participated in an online questionnaire survey. Using structural equation modeling, our results supported the hypothesized reciprocal model, indicating that strength use can significantly predict a reduction in depressive symptoms and vice versa. Given these findings, there's an urgent need for nurse leaders to emphasize the importance of using nurses' strengths as a strategy to alleviate depressive symptoms.

DIA proteomics analysis reveals the mechanism of folic acid-induced acute kidney injury and the effects of icariin.

The complexities of acute kidney injury (AKI), a multifaceted pathological occurrence, are not fully understood. At present, there is a lack of effective pharmaceutical treatments in clinical practice. Studies have shown that icariin has beneficial effects in models of acute kidney injury (AKI) caused by cisplatin and lipopolysaccharide (LPS). The aim is to explore the mechanisms that cause folic acid (FA)-induced AKI and examine the protective effects of icariin against this condition. To establish a mouse model of AKI, FA was administered via intraperitoneal injection. Icariin was used as the drug intervention. The model and the impact of drug intervention were assessed using measurements of renal function parameters, staining with hematoxylin and eosin, and Q-PCR. The analysis of protein expression changes in the control, model, and icariin treatment groups was conducted using proteomics. KEGG signaling pathway analysis indicates that differential expressed proteins are enriched in the component and coagulation cascades signaling pathway. Through protein-protein interaction network analysis, it was found that compared to the normal group, the expression of Fibrinogen and other proteins was significantly upregulated at the center of the protein interaction network in the model group. After drug treatment, the expression of these proteins was significantly downregulated. The validation experiment supports the above results. In conclusion, this study clarified the molecular mechanism of FA induced acute renal injury from the proteomics level, and provided target selection for AKI; At the same time, the mechanism of icariin in the treatment of AKI was analyzed from the proteomics level.

Lineage regulators TFAP2C and NR5A2 function as bipotency activators in totipotent embryos.

During the first lineage segregation, a mammalian totipotent embryo differentiates into the inner cell mass (ICM) and trophectoderm (TE). However, how transcription factors (TFs) regulate this earliest cell-fate decision in vivo remains elusive, with their regulomes primarily inferred from cultured cells. Here, we investigated the TF regulomes during the first lineage specification in early mouse embryos, spanning the pre-initiation, initiation, commitment, and maintenance phases. Unexpectedly, we found that TFAP2C, a trophoblast regulator, bound and activated both early TE and inner cell mass (ICM) genes at the totipotent (two- to eight-cell) stages ('bipotency activation'). Tfap2c deficiency caused downregulation of early ICM genes, including Nanog, Nr5a2, and Tdgf1, and early TE genes, including Tfeb and Itgb5, in eight-cell embryos. Transcription defects in both ICM and TE lineages were also found in blastocysts, accompanied by increased apoptosis and reduced cell numbers in ICMs. Upon trophoblast commitment, TFAP2C left early ICM genes but acquired binding to late TE genes in blastocysts, where it co-bound with CDX2, and later to extra-embryonic ectoderm (ExE) genes, where it cooperatively co-occupied with the former ICM regulator SOX2. Finally, 'bipotency activation' in totipotent embryos also applied to a pluripotency regulator NR5A2, which similarly bound and activated both ICM and TE lineage genes at the eight-cell stage. These data reveal a unique transcription circuity of totipotency underpinned by highly adaptable lineage regulators.