Incremental Effectiveness of Emergency Vaccination Against a Varicella Outbreak at an Elementary School in Beijing, China, 2019: An Observational Cohort Study.

(1) Background: The effect of varicella emergency vaccination (EV) has not been fully evaluated. (2) Methods: This was a cohort study. Participants were categorized into five groups based on their immune status: unvaccinated group, first dose as EV group, one dose no EV group, second dose as EV group, and two doses no EV group. A Cox proportional hazards model was employed to examine the association between the EV measures and the varicella incidence rate in this outbreak. (3) Results: Demographic characteristics, vaccination details, and disease onset information were 100% (918/918) collected. The crude attack rate was 44% (11/25), 8% (3/36), 11% (24/215), 3% (6/176), and 2% (8/466) among the unvaccinated group, first dose as EV group, one dose no EV group, second dose as EV group and two doses no EV group, respectively. Compared to the unvaccinated group and the one dose no EV group, the first dose varicella vaccine as EV and the second dose as EV demonstrated an incremental effectiveness of 90% (95% CI 65-97%) and 79% (95% CI 47-92%), respectively. (4) Conclusions: Both the first dose and the second dose as EV contributed to reducing the incidence rates of varicella and offered incremental vaccine effectiveness in an outbreak setting. Our study underscores the importance and benefits of initiating emergency varicella vaccination early to reduce the disease incidence rate in an elementary school setting where there was no complete coverage of the two doses of varicella vaccine and an outbreak occurred.

Hypoxic Preconditioned ADSC Exosomes Enhance Vaginal Wound Healing via Accelerated Keratinocyte Proliferation and Migration Through AKT/HIF­1α Axis Activation.

Purpose: Accelerating wound healing is a main consideration in surgery. The three stages of wound healing are inflammatory response, tissue repair and cell proliferation. Much research has focused on epidermal cell proliferation and migration because this is an essential step in wound healing. Methods and Results: The current study discovered that exosomes from Adipose-derived stem cell (ADSC) following hypoxic preconditioning (HExo) have a greater promotional effect on vaginal wound healing. Protein kinase B (AKT)/hypoxia-inducible factor 1-alpha (HIF-1α) play an important role in HExo-mediated HaCaT cell migration and proliferation. The promotional effect of HExo on rat wound healing was reversed by both, HIF­1α and AKT inhibition. Phosphorylation of AKT (p-AKT) or HIF­1α suppression reversed the protective effect of HExo on vaginal wound healing. Conclusion: Taken together, our study found that hypoxic preconditioning of adipose MSC exosomes enhances vaginal wound healing via accelerated keratinocyte proliferation and migration through AKT/HIF­1α axis activation.

TMEM56 deficiency impairs the haem metabolism and cell cycle progression during human erythropoiesis.

TMEM56, a gene coding a transmembrane protein, is abundantly expressed in erythroid cells. Despite this, its role in erythropoiesis has not been well characterized. In this study, we sought to clarify the function of TMEM56 in erythroid development, focusing specifically on its involvement in haem biosynthesis and cell cycle progression. To do this, we used CD34+ haematopoietic stem cells derived from umbilical cord blood and differentiated them into erythroid cells in an ex vivo model. Our results indicate that the loss of TMEM56 disrupts haem biosynthesis and impairs erythroid differentiation. Furthermore, deletion of Tmem56 in the erythroid lineage in murine models using erythropoietin receptor (EpoR)-Cre revealed defects in erythroid progenitors within the bone marrow under both normal conditions and during haemolytic anaemia. These observations underscore the regulatory role of TMEM56 in maintaining erythroid lineage homeostasis. Taken together, our results unveil a previously unrecognized function of TMEM56 in erythroid differentiation and suggest its potential as an unfounded target for therapeutic strategies in the treatment of erythropoietic disorders.

Solvothermal Preparation of Crystal Seeds and Anisotropy-Controlled Growth of Silver Nanoplates.

We synthesized silver nanoplates using the solvothermal method and, for the first time, placed them as crystal seeds in a water-based growth solution, thereby successfully achieving the large-scale production of silver nanoplates. The synthesis method enabled independent control of the lateral size and vertical size of the silver nanoplates. More specifically, the lateral size could be adjusted within the range of 565 nm-1.682 µm, while the vertical size was achieved by introducing Cl- as a capping agent and the vertical size was thickened from 18.28 to 40.41 nm.

Personalized and continuous care intervention affects rehabilitation, living quality, and negative emotions of patients with breast cancer.

BACKGROUND: Breast cancer is among the most common malignancies worldwide. With progress in treatment methods and levels, the overall survival period has been prolonged, and the demand for quality care has increased. AIM: To investigate the effect of individualized and continuous care intervention in patients with breast cancer. METHODS: Two hundred patients with breast cancer who received systemic therapy at The First Affiliated Hospital of Hebei North University (January 2021 to July 2023) were retrospectively selected as research participants. Among them, 134 received routine care intervention (routing group) and 66 received personalized and continuous care (intervention group). Self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Functional Assessment of Cancer Therapy-Breast (FACT-B) scores, including limb shoulder joint activity, complication rate, and care satisfaction, were compared between both groups after care. RESULTS: SAS and SDS scores were lower in the intervention group than in the routing group at one and three months after care. The total FACT-B scores and five dimensions in the intervention group were higher than those in the routing group at three months of care. The range of motion of shoulder anteflexion, posterior extension, abduction, internal rotation, and external rotation in the intervention group was higher than that in the routing group one month after care. The incidence of postoperative complications was 18.18% lower in the intervention group than in the routing group (34.33%; P <0.05). Satisfaction with care was 90.91% higher in the intervention group than in the routing group (78.36%; P <0.05). CONCLUSION: Personalized and continuous care can alleviate negative emotions in patients with breast cancer, quicken rehabilitation of limb function, decrease the incidence of complications, and improve living quality and care satisfaction.

Development of a clinical prognostic model for primary plasma cell leukemia patients treated with novel agents: a multicenter retrospective cohort study.

The prognosis of primary plasma cell leukemia (pPCL) is poor, and the relevant prognostic factors are incompletely understood. We aimed to explore the prognostic factors and develop a validated prognostic prediction model for pPCL patients in the new era. This multicenter retrospective study was conducted across 16 hospitals in China. Cox proportional hazards regression analysis was used to develop a prediction model. The predictive performance of the model was assessed using multiple metrics. Internal validation was conducted using bootstrap resampling. A total of 102 pPCL patients were included in this study, and 57 (55.9%) were male. The 12-month, 24-month, and 36-month OS rates for pPCL patients were 75.4%, 58.3%, and 47.6%, respectively. An overall survival prognostic nomogram for pPCL patients was established by integrating independent prognostic factors, including age, B2MG, and del17p. The nomogram exhibited good performance, with a C-index of 0.720 (95% CI 0.642-0.797) and an AUC of 0.653. Bootstrap validation yielded a C-index of 0.721 (95% CI 0.629-0.787) and an AUC of 0.653 (95% CI 0.546-0.759), indicating a relatively good fit of the calibration curve. A nomogram incorporating age, B2MG grade, and del17p were developed and validated to accurately and consistently predict the prognosis of pPCL patients.

Comprehensive analysis of Alfin-like transcription factors associated with drought and salt stresses in wheat (Triticum aestivum L.).

BACKGROUND: Alfin-like proteins are a kind of plant-specific transcription factors, and play vital roles in plant growth, development and stress responses. RESULTS: In this study, a total of 27 Alfin-like transcription factors were identified in wheat. TaAL genes were unevenly distributed on chromosome. Phylogenetic analysis showed TaAL genes were divided into AL-B and AL-C subfamilies, and TaALs with closer evolutionary relationships generally shared more similar exon-intron structures and conserved motifs. The cis-acting element analysis showed MBS, ABRE and CGTCA-motif were the most common in TaAL promoters. The interacting proteins and downstream target genes of TaAL genes were also investigated in wheat. The transcriptome data and real-time PCR results indicated TaAL genes were differentially expressed under drought and salt stresses, and TaAL1-B was significantly up-regulated in response to drought stress. In addition, association analysis revealed that TaAL1-B-Hap-I allelic variation had significantly higher survival rate compared to TaAL1-B-Hap-II under drought stress. CONCLUSIONS: These results will provide vital information to increase our understanding of the Alfin-like gene family in wheat, and help us in breeding better wheat varieties in the future.

Loss of Tet hydroxymethylase activity causes mouse embryonic stem cell differentiation bias and developmental defects.

The TET family is well known for active DNA demethylation and plays important roles in regulating transcription, the epigenome and development. Nevertheless, previous studies using knockdown (KD) or knockout (KO) models to investigate the function of TET have faced challenges in distinguishing its enzymatic and nonenzymatic roles, as well as compensatory effects among TET family members, which has made the understanding of the enzymatic role of TET not accurate enough. To solve this problem, we successfully generated mice catalytically inactive for specific Tet members (Tetm/m). We observed that, compared with the reported KO mice, mutant mice exhibited distinct developmental defects, including growth retardation, sex imbalance, infertility, and perinatal lethality. Notably, Tetm/m mouse embryonic stem cells (mESCs) were successfully established but entered an impaired developmental program, demonstrating extended pluripotency and defects in ectodermal differentiation caused by abnormal DNA methylation. Intriguingly, Tet3, traditionally considered less critical for mESCs due to its lower expression level, had a significant impact on the global hydroxymethylation, gene expression, and differentiation potential of mESCs. Notably, there were common regulatory regions between Tet1 and Tet3 in pluripotency regulation. In summary, our study provides a more accurate reference for the functional mechanism of Tet hydroxymethylase activity in mouse development and ESC pluripotency regulation.

Thermostable vacuum foam dried Newcastle disease vaccine: Process optimization and pilot-scale study.

Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13-17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log10 with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log10 (approximately 1.1 log10). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log10. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future. KEY POINTS: • The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study. • The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions. • The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.

Systematic Analysis of Zinc Finger-Homeodomain Transcription Factors (ZF-HDs) in Barley (Hordeum vulgare L.).

Zinc finger-homeodomain transcription factors (ZF-HDs) are pivotal in regulating plant growth, development, and diverse stress responses. In this study, we found 8 ZF-HD genes in barley genome. Theses eight HvZF-HD genes were located on five chromosomes, and classified into ZHD and MIF subfamily. The collinearity, gene structure, conserved motif, and cis-elements of HvZF-HD genes were also analyzed. Real-time PCR results suggested that the expression of HvZF-HD4, HvZF-HD6, HvZF-HD7 and HvZF-HD8 were up-regulated after hormones (ABA, GA3 and MeJA) or PEG treatments, especially HvZF-HD6 was significantly induced. These results provide useful information of ZF-HD genes to future study aimed at barley breeding.

Male-pronuclei-specific granulin facilitates somatic cells reprogramming via mitigating excessive cell proliferation and enhancing lysosomal function.

Critical reprogramming factors resided predominantly in the oocyte or male pronucleus can enhance the efficiency or the quality of induced pluripotent stem cells (iPSCs) induction. However, few reprogramming factors exist in the male pronucleus had been verified. Here, we demonstrated that granulin (Grn), a factor enriched specifically in male pronucleus, can significantly improve the generation of iPSCs from mouse fibroblasts. Grn is highly expressed on Day 1, Day 3, Day 14 of reprogramming induced by four Yamanaka factors and functions at the initial stage of reprogramming. Transcriptome analysis indicates that Grn can promote the expression of lysosome-related genes, while inhibit the expression of genes involved in DNA replication and cell cycle at the early reprogramming stage. Further verification determined that Grn suppressed cell proliferation due to the arrest of cell cycle at G2/M phase. Moreover, ectopic Grn can enhance the lysosomes abundance and rescue the efficiency reduction of reprogramming resulted from lysosomal protease inhibition. Taken together, we conclude that Grn serves as an activator for somatic cell reprogramming through mitigating cell hyperproliferation and promoting the function of lysosomes.

Defining a TFAP2C-centered transcription factor network during murine peri-implantation.

Transcription factors (TFs) play important roles in early embryonic development, but factors regulating TF action, relationships in signaling cascade, genome-wide localizations, and impacts on cell fate transitions during this process have not been clearly elucidated. In this study, we used uliCUT&RUN-seq to delineate a TFAP2C-centered regulatory network, showing that it involves promoter-enhancer interactions and regulates TEAD4 and KLF5 function to mediate cell polarization. Notably, we found that maternal retinoic acid metabolism regulates TFAP2C expression and function by inducing the active demethylation of SINEs, indicating that the RARG-TFAP2C-TEAD4/KLF5 axis connects the maternal-to-zygotic transition to polarization. Moreover, we found that both genomic imprinting and SNP-transferred genetic information can influence TF positioning to regulate parental gene expressions in a sophisticated manner. In summary, we propose a ternary model of TF regulation in murine embryonic development with TFAP2C as the core element and metabolic, epigenetic, and genetic information as nodes connecting the pathways.

Melatonin promotes proliferation of Inner Mongolia cashmere goat hair follicle papilla cells through Wnt10b.

The study demonstrated that melatonin (MT) can induce the development of secondary hair follicles in Inner Mongolian cashmere goats through the Wnt10b gene, leading to secondary dehairing. However, the mechanisms underlying the expression and molecular function of Wnt10b in dermal papilla cells (DPC) remain unknown. This research aimed to investigate the impact of MT on DPC and the regulation of Wnt10b expression, function, and molecular mechanisms in DPC. The findings revealed that MT promotes DPC proliferation and enhances DPC activity. Co-culturing DPC with overexpressed Wnt10b and MT showed a significant growth promotion. Subsequent RNA sequencing (RNA-seq) of overexpressed Wnt10b and control groups unveiled the regulatory role of Wnt10b in DPC. Numerous genes and pathways, including developmental pathways such as Wnt and MAPK, as well as processes like hair follicle morphogenesis and hair cycle, were identified. These results suggest that Wnt10b promotes the growth of secondary hair follicles in Inner Mongolian cashmere goats by regulating crucial factors and pathways in DPC proliferation.

Chromatin landscape instructs precise transcription factor regulome during embryonic lineage specification.

Embryos, originating from fertilized eggs, undergo continuous cell division and differentiation, accompanied by dramatic changes in transcription, translation, and metabolism. Chromatin regulators, including transcription factors (TFs), play indispensable roles in regulating these processes. Recently, the trophoblast regulator TFAP2C was identified as crucial in initiating early cell fate decisions. However, Tfap2c transcripts persist in both the inner cell mass and trophectoderm of blastocysts, prompting inquiry into Tfap2c's function in post-lineage establishment. In this study, we delineate the dynamics of TFAP2C during the mouse peri-implantation stage and elucidate its collaboration with the key lineage regulators CDX2 and NANOG. Importantly, we propose that de novo formation of H3K9me3 in the extraembryonic ectoderm during implantation antagonizes TFAP2C binding to crucial developmental genes, thereby maintaining its lineage identity. Together, these results highlight the plasticity of the chromatin environment in designating the genomic binding of highly adaptable lineage-specific TFs and regulating embryonic cell fates.

Effectiveness of a Teach-Back Education Program on Perioperative Pain in Patients With Lung Cancer: An Intervention Study Using Behavior Change Wheel.

OBJECTIVE: To assess the effect of a teach-back educational intervention using Behavior Change Wheel (BCW) framework on perioperative pain among patients with lung cancer. METHODS: A prospective quasi-experimental study was conducted in 88 patients with lung cancer from a tertiary hospital in China. According to the order of admission, they were allocated to either control group or intervention group, with 44 patients in each group. Patients in the control group received routine nursing care, while patients in the intervention group were given a teach-back education program based on BCW framework. The visual analog scale (VAS) was adopted to evaluate patients' pain on the day of surgery (T0), 1 (T1), 2 (T2), and 3 (T3) days after surgery. We also recorded the use of patient-controlled analgesia (PCA), the length of hospital stay, and the degree of patients' satisfaction. RESULTS: Rest pain, pain when coughing, and pain during activity that patients in the intervention group experienced were significantly less severe than those in the control group on T0 and T1. The pain when coughing in the intervention group was also significantly milder on T2 and T3. In addition, the number of self-control time, use duration, and total dose of PCA were significantly lower in the intervention group. Moreover, patients' satisfaction of nursing service was significantly higher in the intervention group. CONCLUSION: A teach-back education program based on BCW framework was effective in pain management among the perioperative patients with lung cancer. This study demonstrates the application of teach-back method and the BCW in the development of patient education intervention to mitigate perioperative pain.

Relationship of serum total cholesterol and triglyceride with risk of mortality in maintenance hemodialysis patients: a multicenter prospective cohort study.

OBJECTIVE: The relationship between serum total cholesterol (TC) and triglyceride (TG) levels and mortality in maintenance hemodialysis (MHD) patients remains inconsistent. We aimed to explore the individual and combined association of TC and TG levels with the risk of mortality in Chinese MHD patients. METHODS: 1036 MHD patients were enrolled in this multicenter, prospective cohort study. The serum levels of total cholesterol and triglycerides were measured at baseline. The primary outcome was all-cause mortality and secondary outcome was cardiovascular disease (CVD) mortality. RESULTS: During a median follow-up duration of 4.4 years (IQR= 2.0-7.9 years), 549 (53.0%) patients died, and 297 (28.7%) deaths were attributed to CVD. Compared with patients with TC levels in the first three quartiles (<182.5 mg/dL), a significantly higher risk of all-cause mortality was found in participants with TC in the fourth quartile (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.17-1.76). However, a significantly lower risk of all-cause mortality was observed in participants with TG in the fourth quartile (≥193.9 mg/dL) (HR, 0.78; 95%CI: 0.63-0.98), compared with participants with TG in the first three quartiles. Similar trends were observed in CVD mortality. When analyzed jointly, patients with lower TC (<182.5 mg/dL) and higher TG (≥193.9 mg/dL) levels had the lowest risk of all-cause mortality and CVD mortality.Conclusions: In MHD patients in southern China, higher TC levels were associated with higher risk of mortality, while higher TG levels were related to lower risk of mortality. Patients with lower TC and higher TG levels had the best survival prognosis.

ADNP modulates SINE B2-derived CTCF-binding sites during blastocyst formation in mice.

CTCF is crucial for chromatin structure and transcription regulation in early embryonic development. However, the kinetics of CTCF chromatin occupation in preimplantation embryos have remained unclear. In this study, we used CUT&RUN technology to investigate CTCF occupancy in mouse preimplantation development. Our findings revealed that CTCF begins binding to the genome prior to zygotic genome activation (ZGA), with a preference for CTCF-anchored chromatin loops. Although the majority of CTCF occupancy is consistently maintained, we identified a specific set of binding sites enriched in the mouse-specific short interspersed element (SINE) family B2 that are restricted to the cleavage stages. Notably, we discovered that the neuroprotective protein ADNP counteracts the stable association of CTCF at SINE B2-derived CTCF-binding sites. Knockout of Adnp in the zygote led to impaired CTCF binding signal recovery, failed deposition of H3K9me3, and transcriptional derepression of SINE B2 during the morula-to-blastocyst transition, which further led to unfaithful cell differentiation in embryos around implantation. Our analysis highlights an ADNP-dependent restriction of CTCF binding during cell differentiation in preimplantation embryos. Furthermore, our findings shed light on the functional importance of transposable elements (TEs) in promoting genetic innovation and actively shaping the early embryo developmental process specific to mammals.

Prevalence and Risk Factors of Diabetes in Patients with Active Pulmonary Tuberculosis: A Cross-Sectional Study in Two Financially Affluent China Cities.

Background: Tuberculosis (TB) and diabetes mellitus (DM) present a dual burden to public health. The screening of DM in TB patients may aid in the early detection and management of diabetes, ultimately improving treatment outcomes for those with the comorbidity of TB-DM. We aim to examine the prevalence and identify risk factors of diabetes in individuals with active pulmonary tuberculosis (PTB) in financially affluent China cities. Methods: A cross-sectional survey was conducted in adult patients with highly suspected TB in two cities of China, spanning from May 9, 2023, to June 30, 2023. We compare the clinical characteristics, nutrition status, fasting blood glucose (FBG) level, living style, and knowledge of TB and DM at admission between patients with and without DM. Univariate and multivariate logistic regression analyses were employed to identify risk factors associated with TB-DM comorbidities. Results: Of the 322 patients diagnosed with pulmonary tuberculosis (PTB), 54 individuals (16.8%) had comorbid diabetes mellitus (DM). This included 43 males (13.4%) and 11 females (3.4%). The average age was 55.44 ± 12.36 in DM patients and 46.09 ± 16.87 in non-DM patients. A multivariate logistic regression analysis revealed that male (adjusted odds ratio [aOR]=3.29, 95% confidence interval [CI]: 1.05-10.30), age older than 47 years (aOR = 1.04, 95% CI: 1.01-1.07), having a family history of diabetes (aOR = 5.09, 95% CI: 1.28-20.32), and an elevated random blood glucose level (aOR = 1.6, 95% CI: 1.38-1.86) were risk factors for DM in patients with PTB. Furthermore, it was found that diabetes awareness (aOR = 0.07, 95% CI: 0.03-0.21) and zero, light to moderate alcohol consumption were associated with a lower risk of diabetes. Conclusion: Diabetes is prevalent in patients with active PTB. Screening and raising awareness of DM are recommended, particularly in men after middle age with a family history of diabetes and elevated random blood glucose. Early diagnosis of diabetes and effective diabetes prevention may reduce the dual burden of TB-DM comorbidity.

Transplantation of the LRP1high subpopulation of human umbilical cord-derived mesenchymal stem cells improves ovarian function in mice with premature ovarian failure and aged mice.

BACKGROUND: Premature ovarian failure (POF) has a profound impact on female reproductive and psychological health. In recent years, the transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) has demonstrated unprecedented potential in the treatment of POF. However, the heterogeneity of human UC-MSCs remains a challenge for their large-scale clinical application. Therefore, it is imperative to identify specific subpopulations within UC-MSCs that possess the capability to improve ovarian function, with the aim of reducing the uncertainty arising from the heterogeneity while achieving more effective treatment of POF. METHODS: 10 × Genomics was performed to investigate the heterogeneity of human UC-MSCs. We used LRP1 as a marker and distinguished the potential therapeutic subpopulation by flow cytometry, and determined its secretory functions. Unsorted UC-MSCs, LRP1high and LRP1low subpopulation was transplanted under the ovarian capsules of aged mice and CTX-induced POF mice, and therapeutic effects was evaluated by assessing hormone levels, estrous cycles, follicle counts, and embryo numbers. RNA sequencing on mouse oocytes and granulosa cells after transplantation was performed to explore the mechanism of LRP1high subpopulation on mouse oocytes and granulosa cells. RESULTS: We identified three distinct functional subtypes, including mesenchymal stem cells, multilymphoid progenitor cells and trophoblasts. Additionally, we identified the LRP1high subpopulation, which improved ovarian function in aged and POF mice. We elucidated the unique secretory functions of the LRP1high subpopulation, capable of secreting various chemokines, cytokines, and growth factors. Furthermore, LRP1 plays a crucial role in regulating the ovarian microenvironment, including tissue repair and extracellular matrix remodeling. Consistent with its functions, the transcriptomes of oocytes and granulosa cells after transplantation revealed that the LRP1high subpopulation improves ovarian function by modulating the extracellular matrix of oocytes, NAD metabolism, and mitochondrial function in granulosa cells. CONCLUSION: Through exploration of the heterogeneity of UC-MSCs, we identified the LRP1high subpopulation capable of improving ovarian function in aged and POF mice by secreting various factors and remodeling the extracellular matrix. This study provides new insights into the targeted exploration of human UC-MSCs in the precise treatment of POF.

Pivotal role for long noncoding RNAs in zygotic genome activation in mice.

Vertebrate life begins with fertilization, and then the zygote genome is activated after transient silencing, a process termed zygotic genome activation (ZGA). Despite its fundamental role in totipotency and the initiation of life, the precise mechanism underlying ZGA initiation remains unclear. The existence of minor ZGA implies the possible critical role of noncoding RNAs in the initiation of ZGA. Here, we delineate the expression profile of long noncoding RNAs (lncRNAs) in early mouse embryonic development and elucidate their critical role in minor ZGA. Compared with protein-coding genes (PCGs), lncRNAs exhibit a stronger correlation with minor ZGA. Distinct H3K9me3 profiles can be observed between lncRNA genes and PCGs, and the enrichment of H3K9me3 before ZGA might explain the suspended expression of major ZGA-related PCGs despite possessing PolII pre-configuration. Furthermore, we identified the presence of PolII-enriched MuERV-L around the transcriptional start site of minor ZGA-related lncRNAs, and these repeats are responsible for the activation of minor ZGA-related lncRNAs and subsequent embryo development. Our study suggests that MuERV-L mediates minor ZGA lncRNA activation as a critical driver between epigenetic reprogramming triggered by fertilization and the embryo developmental program, thus providing clues for understanding the regulatory mechanism of totipotency and establishing bona fide totipotent stem cells.