Single-embryo transcriptomic atlas of oxygen response reveals the critical role of HIF-1α in prompting embryonic zygotic genome activation.

Adaptive response to physiological oxygen levels (physO2; 5% O2) enables embryonic survival in a low-oxygen developmental environment. However, the mechanism underlying the role of physO2 in supporting preimplantation development, remains elusive. Here, we systematically studied oxygen responses of hallmark events in preimplantation development. Focusing on impeded transcriptional upregulation under atmospheric oxygen levels (atmosO2; 20% O2) during the 2-cell stage, we functionally identified a novel role of HIF-1α in promoting major zygotic genome activation by serving as an oxygen-sensitive transcription factor. Moreover, during blastocyst formation, atmosO2 impeded H3K4me3 and H3K27me3 deposition by deregulating histone-lysine methyltransferases, thus impairing X-chromosome inactivation in blastocysts. In addition, we found atmosO2 impedes metabolic shift to glycolysis before blastocyst formation, thus resulting a low-level histone lactylation deposition. Notably, we also reported an increased sex-dimorphic oxygen response of embryos upon preimplantation development. Together, focusing on genetic and epigenetic events that are essential for embryonic survival and development, the present study advances current knowledge of embryonic adaptive responses to physO2, and provides novel insight into mechanism underlying irreversibly impaired developmental potential due to a short-term atmosO2 exposure.

Latent class analysis of Chinese healthcare providers' attitudes towards oocyte cryopreservation: a cross-sectional study.

OBJECTIVES: The present study was designed to examine the attitudes towards oocyte cryopreservation among healthcare providers working in hospitals across specialties and potential influencing factors. DESIGN: A cross-sectional study. SETTING: The questionnaire was distributed among Chinese healthcare providers via the Credamo platform. PARTICIPANTS: There were 877 respondents recruited from 8 April to 8 May 2022, among whom 160 were identified as unqualified because of inconsistency between the IP and work addresses. OUTCOME MEASURES: Individual attitudes towards oocyte cryopreservation under four different settings, familiarity with oocyte cryopreservation and perceived risks about oocyte cryopreservation of healthcare providers were measured using a self-designed questionnaire. RESULTS: There were 877 respondents recruited, and 717 were identified as qualified respondents. Two latent classes of healthcare providers characterised by different attitudes towards oocyte cryopreservation under four different settings were identified, the supportive and reluctant. Familiarity with oocyte cryopreservation had a significant direct effect on perceived risks, with better familiarity predicting lower perceived risks (ß=-0.102, p<0.05). Perceived risks showed a significant direct effect on participants' attitudes towards oocyte cryopreservation, with higher perceived risks predicting a more reluctant attitude (ß=0.165, p<0.001). CONCLUSIONS: The majority of healthcare providers held a reluctant attitude towards oocyte cryopreservation of unmarried women for non-medical reasons, which might relate to their worries about the risks to offspring's health and lack of knowledge about a reproductive technique.

Social egg freezing and reproductive rights justification: A perspective from China.

Divergences and controversies are inevitable in the discussion of freedoms and rights, especially in the matter of reproduction. The Chinese first social egg freezing lawsuit raises the question: is the freedom to freeze eggs for social reasons justified because it is an instance of reproductive rights? This paper accepts social egg freezing as desirable reproductive freedom, but following Harel's approach and considering two theories of rights, the choice and interest theories of rights, we argue that social egg freezing is not a reproductive right because one cannot justify a right or an instance of rights via merely describing the function of those instances that have been justified as right, that is, the choice theory lacks justifying normativity. Since reserving fertility and a suspension from reproduction do not serve reproductive ends per se, the sufficient reason for demanding social egg freezing as a right should be found in other ends rather than in right-to-reproduce, that is, the interest theory denies the demand as a right-to-reproduce. Permitting it on any grounds without guaranteeing adequate and accessible resources, especially in light of cross-border reproductive care, raises serious questions about reproductive equality and violates the idea of reproductive rights. Therefore, any ground for social egg freezing should be weighed against whether more pressing reproductive needs, specifically those that are justified as rights, have been met. It would be social progress to shoulder these burdens for the vulnerable and then allow social egg freezing-if right-to-reproduce were not the only privilege of the few.

Glutathione safeguards TET-dependent DNA demethylation and is critical for the acquisition of totipotency and pluripotency during preimplantation development.

During early development, both genome-wide epigenetic reprogramming and metabolic remodeling are hallmark changes of normal embryogenesis. However, little is known about their relationship and developmental functions during the preimplantation window, which is essential for the acquisition of totipotency and pluripotency. Herein, we reported that glutathione (GSH), a ubiquitous intracellular protective antioxidant that maintains mitochondrial function and redox homeostasis, plays a critical role in safeguarding postfertilization DNA demethylation and is essential for establishing developmental potential in preimplantation embryos. By profiling mitochondria-related transcriptome that coupled with different pluripotency, we found GSH is a potential marker that is tightly correlated with full pluripotency, and its beneficial effect on prompting developmental potential was functionally conformed using in vitro fertilized mouse and bovine embryos as the model. Mechanistic study based on preimplantation embryos and embryonic stem cells further revealed that GSH prompts the acquisition of totipotency and pluripotency by facilitating ten-eleven-translocation (TET)-dependent DNA demethylation, and ascorbic acid (AsA)-GSH cycle is implicated in the process. In addition, we also reported that GSH serves as an oviductal paracrine factor that supports development potential of preimplantation embryos. Thus, our results not only advance the current knowledge of functional links between epigenetic reprogramming and metabolic remodeling during preimplantation development but also provided a promising approach for improving current in vitro culture system for assisted reproductive technology.

Individualized Implementation of Youth Quality of Life Instrument-Research Version (YQOL-R) Among Chinese Adolescents with Different Weight Status.

Purpose: This study implemented the individualized Youth Quality of Life Instrument-Research Version (YQOL-R) to estimate the quality of life (QoL) among Chinese adolescents with three different Body Mass Index (BMI) levels. The study aims to explore and provide a reference for developing individualized QoL (IQoL) measurements in China. Methods: The sample consisted of 822 aged 11-18 from nine schools. The data collection included all participants' primary characters (age, sex, annual household income, parental education, and recruitment community) and their self-report QoL. Precisely, based on the generic measurement of YQOL-R, we developed IQoL measurements by asking adolescents' perceived five most important things to them (IQOLimportance) and the aspects they most want to change (IQOLchange) from 19 facets, respectively. The one-way analysis of variance (ANOVA) was applied to compare total and subscale scores of IQOLimportance, IQOLchange, and YQOL-R among adolescents with three different weight status. Also, the data analysis used multivariable linear regression modeling to test the effects on scores of IQOLimportance and IQOLchange. Results: Overall, the obese adolescents identified "Having good physical health" as the most important (54.03%) and most like-to-change (42.65%); in contrast, the normal-weight group ranked "Being myself" as the top facet of IQOLimportance (52.42%) and "Having good friends" as the top facet of IQOLchange (43.12%). The obese adolescents' reported IQOLimportance scores are significantly lower than those of the normal-weight group (P=0.039). However, there is no significant difference in IQOLchange score among the three weight-status groups. The multivariable linear regression models indicated that adolescents who are girls (P=0.035), have higher educated fathers (P=0.049), and are overweight/obese (P=0.041) self-reported worse IQOLimportance score; yet, the girls (P=0.023) and older adolescents (P=0.004) answered lower IQOLchange scores. In addition, adolescents who had higher educated mothers (P=0.047; 0.023) and responded with higher total YQOL-R scores (P<0.001; <0.001) reported higher IQOLimportance and IQOLchange scores. Conclusion: In the current study, although the self-reported YQOL-R scores from different weight status did not present a significant difference, the obese group reported a statistical trend towards lower IQOLimportance scores than the normal-weight and overweight adolescents. These findings emphasize that IQOLimportance and IQOLchange could capture adolescents' perspectives with different weight statuses about their lives, which are unique as complementary health outcomes accompanying YQOL-R in health surveys and interventions among Chinese adolescents.

The Vulnerability of International Floating Populations to Sexually Transmitted Infections: A Qualitative Study.

With the rapid development of the global economy, along with globalisation, the health of international floating populations (especially their sexual health) has become a problem that cannot be ignored. This study explored the potential vulnerability of international floating populations to sexually transmitted infections (STIs) from the points of view of society, religion, culture, migration, community environment, and personal behaviours. In-depth exploratory interviews with 51 members of the international floating population living in China were conducted in June and July 2022. A qualitative thematic analysis methodology was used to analyse the content of these interviews. We found that a conservative culture orientated around religion leads to a lack of sex education, resulting in insufficient personal knowledge as well as a lack of the motivation and awareness required to encourage condom use during sexual contact. Additionally, both geographical isolation and reduced social supervision have expanded personal space, which has led to social isolation and marginalisation, in addition to challenges for coping with STI risk. These factors have increased the possibility of individuals engaging in risky behaviours.

WNT Co-Receptor LRP6 Is Critical for Zygotic Genome Activation and Embryonic Developmental Potential by Interacting with Oviductal Paracrine Ligand WNT2.

Mammalian preimplantation development depends on the interaction between embryonic autocrine and maternal paracrine signaling. Despite the robust independence of preimplantation embryos, oviductal factors are thought to be critical to pregnancy success. However, how oviductal factors regulate embryonic development and the underlying mechanism remain unknown. In the present study, focusing on WNT signaling, which has been reported to be essential for developmental reprogramming after fertilization, we analyzed the receptor-ligand repertoire of preimplantation embryonic WNT signaling, and identified that the WNT co-receptor LRP6 is necessary for early cleavage and has a prolonged effect on preimplantation development. LRP6 inhibition significantly impeded zygotic genome activation and disrupted relevant epigenetic reprogramming. Focusing on the potential oviductal WNT ligands, we found WNT2 as the candidate interacting with embryonic LRP6. More importantly, we found that WNT2 supplementation in culture medium significantly promoted zygotic genome activation (ZGA) and improved blastocyst formation and quality following in vitro fertilization (IVF). In addition, WNT2 supplementation significantly improved implantation rate and pregnancy outcomes following embryo transfer. Collectively, our findings not only provide novel insight into how maternal factors regulate preimplantation development through maternal-embryonic communication, but they also propose a promising strategy for improving current IVF systems.

Ethical conflict in nursing: A concept analysis.

AIMS AND OBJECTIVES: The purpose of this paper was to clarify the concept of ethical conflict in nursing and highlight the importance of tackling this issue. BACKGROUND: Ethical conflict is on the rise in the nursing context. It is associated with the compromise of nurses' well-being and patient care. However, there is no thorough conceptual understanding of this concept. DESIGN: Concept analysis. METHODS: Databases (PubMed, PsycINFO, CINAHL, Scopus, Embase, Web of Science and SocINDEX) were searched for studies between 1984 and 2021. Both quantitative and qualitative studies related to ethical conflict in nursing were included. Walker and Avant's method of concept analysis was used to identify the defining attributes, antecedents and consequences of the concept of ethical conflict in nursing. We followed the PRISMA-ScR checklist to report the study. RESULTS: Thirty studies were included for conceptualization. Defining attributes were divided into four categories: (1) emotional responses, (2) incompatible values, (3) competing interests and (4) ambiguous obligations. The antecedents were (1) ethical sensitivity, (2) negative ethical climate, (3) insufficient authority, (4) unrealistic expectations, (5) poor collaboration and (6) inadequate resources. The consequences were identified as (1) moral residue, (2) loss of identity, (3) professional burnout and (4) poor patient care. CONCLUSIONS: A unified conceptual model of ethical conflict in nursing shed light on the ethical issues nurses might come across in practice. Despite the fact that ethical conflict is inherently negative, we conceptualised this concept as a neutral fact and an opportunity for nursing action. The construct identification provides basis for both the development of practice and the development of staff support and education. RELEVANCE TO CLINICAL PRACTICE: A clearer understanding of such an important facet of nursing practice helps nurses raise awareness of ethical conflict and implement effective coping strategies to improve their well-being and patient care. NO PATIENT OR PUBLIC CONTRIBUTION: This is a review article conducted by the researchers, so there is no patient or public contribution.

Leveraging Hydrophilic Hierarchical Channels to Regulate Excessive Water for High-Efficiency Solar Steam Yield.

Both the solar absorptance and water content in solar-driven interface evaporation (SDIE) devices are of equal importance for efficient solar steam yield and freshwater production, but water content regulation has garnered relatively less attention, as it is more challenging to balance the water supply rate and the evaporation rate inside SDIE devices. Herein, an SDIE device is designed by coating natural luffa with polypyrrole, which could effectively regulate the water content during the solar steam yield by its unique hydrophilic hierarchical channels to transform excessive water from the bulk state into the film state on the porous skeleton. The hierarchical channels revealed by cryoelectron microscopy experiments not only reduce the loss of heat in unevaporated water but also offer abundant escape channels for solar steam, thus enabling the proposed SDIE device to achieve an evaporation rate of 2.38 kg m-2 h-1 under 1 sun illumination. This work reveals the key role of hierarchical channels for water regulation in the high-efficiency solar steam yield and triggers further application of natural biomaterials with unique structures in the field of solar interfacial evaporation.

Trehalose can effectively protect sheep epididymis epithelial cells from oxidative stress.

Trehalose, a naturally nontoxic disaccharide that does not exist in mammals, stabilizes cell membrane integrity under oxidative stress conditions, the mechanism of which is still unclear. Here, we analyzed the effects of trehalose on sheep epididymis epithelial cell (EEC) proliferation and its possible mechanisms. To study the effect of trehalose on EECs, EECs were isolated from testes of 12-month-old sheep; cell counting kit-8 (CCK-8) was used to measure the growth of the cells. Cell proliferation was evaluated by assaying cell cycle and apoptosis, and RT-PCR was utilized to identify the epididymal molecular markers glutathione peroxidase 5 (GPX5) and androgen receptor (AR). Next, reactive oxygen species (ROS) content was evaluated by a dichloro-dihydro-fluorescein diacetate (DCFH-DA) probe. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were evaluated by enzyme chemistry methods, and GPX5 expression was evaluated by qRT-PCR and enzyme-linked immunosorbent assay (ELISA). The results showed that 100  mM trehalose significantly improved the proliferation potential of EECs, in which the cells could be serially passaged 14 times with continued normal GPX5 and AR marker gene expression in vitro. The trehalose can increase significantly a proportion of EECs in S phase ( P < 0.01 ) and decrease significantly the apoptotic rate of EECs ( P < 0.01 ) compared to the control. Moreover, the trehalose decreased ROS significantly ( P < 0.01 ) and increased CAT ( P < 0.01 ) and GSH-Px ( P < 0.05 ) activities significantly in EECs. GPX5 mRNA and protein expression were also significantly upregulated in trehalose-treated EECs ( P < 0.05 and P < 0.01 respectively). Our study suggested that exogenous trehalose exhibited antioxidant activity through increasing the activities of CAT, GSH-Px, and the expression level of GPX5 and could be employed to maintain vitality of sheep EECs during long-term in vitro culture.

Eugenics and Mandatory Informed Prenatal Genetic Testing: A Unique Perspective from China.

The application of genetic technologies in China, especially in the area of prenatal genetic testing, is rapidly increasing in China. In the wealthy regions of China, prenatal genetic testing is already very widely adopted. We argue that the government should actively promote prenatal genetic testing to the poor areas of the country. In fact, the government should prioritize resources first to make prenatal genetic testing a standard routine care with an opt-out model in these area. Healthcare professions would be required to inform pregnant women about the availability of genetic testing and provide free testing on a routine basis unless the parents choose not to do so. We argue that this proposal will allow parents to make a more informed decision about their reproductive choices. Secondarily, this proposal will attract more healthcare professionals and other healthcare resources to improve the healthcare infrastructures in the less-developed regions of the country. This will help to reduce the inequity of accessing healthcare services between in different regions of China. We further argue that this policy proposal is not practicing eugenics.

Following the giant's paces-governance issues and bioethical reflections in China.

BACKGROUND: China has become a global player in the field of biosamples research and analysis of genetic data. The Beijing Genomics Institute is a genetics factory where enormous amounts of biosamples/data from all over the world are being analyzed. Most of the global bioethics discussions focused on research conducted by scientists from industrialized countries with subjects from poorer countries. Today, however, samples from industrialized nations are being analyzed in China on an unprecedented scale. This means that one should not just focus on bioethics developments in western countries, but also should pay attention to the situation in China. Under this era of rapid advancement in genomics, reassessing the conventionally accepted bioethical principles is strongly needed. DISCUSSION: In this paper, we will analyze the case of BGI in the context of the Chinese regulatory system in order to identify methods to regulate genetic research more effectively and to strengthen BGI's role in international collaborative research projects. Three main issues concerning sample collection and samples/data management are addressed. Firstly, an ambiguous definition of research, which does not specifically include biosamples/data, when applied to genetic research, may cause confusion and leave loopholes in governance. Secondly, the current regulations do not provide sufficient guidelines on the details of what information to present to prospective subjects, and how to combine informed consent with strategies of re-consent, withdrawal and feedback from research. Finally, the existing regulations do not adequately address issues of genetic privacy and data protection. SUMMARY: Bioethical issues related to genetic research in China may be partially due to the nature of genetic research and partially stems from the strategy of simply adopting general international guidelines into the Chinese context without detailed considerations of the local needs. However, there are no perfect readymade ethical solutions for everyone; every country faces different open questions and challenges behind what appears to be unified guidelines. Given the importance of China in international genetic research, other countries ought to be concerned about the bioethical developments in China. China should also have a substantive discussion with the international community on bioethics issues.