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Abstract Background Nursing is crucial for delivering healthcare services; however, nursing shortages pose a significant global challenge, which the high turnover rate of junior nurses is expected to exacerbate. Enhancing nurses’ professional identities is likely to be an effective strategy for reducing turnover rates. Methods We recruited 865 junior clinical nurses from three tertiary hospitals in Henan Province, China. The participants completed a demographic questionnaire along with the Reflective Ability Scale for Clinical Nurses, the Nursing Profession Self-efficacy Scale, the Nursing Staff Self-learning Ability Evaluation Scale, and the Professional Identity Scale for Nurses. The relationships between reflective ability, self-directed learning, self-efficacy, and professional identity were evaluated using SPSS26.0, with PROCESS version 3.5 used to construct a chain-mediation model. Results Positive correlations were found between reflective ability, self-directed learning, self-efficacy, and professional identity. Chain mediation model analysis showed that reflective ability, self-directed learning, and self-efficacy directly and positively affected professional identity (β = 0.22, β = 0.30, β = 0.66, all p

Abstract Background The efficiency of mesenchymal stem cells (MSCs) in treating myocardial infarction (MI) remains inconsistent, which limits their therapeutic applications. Therefore, exploring the mechanism for the inconsistent efficacy of MSCs and identification the criteria for screening MSCs are important for improving the efficiency of MSCs. Methods Mouse model after MI was utilized to test the role of MSCs from different donors and the functional subpopulation in improving cardiac function. Heterogeneity of MSCs was identified using single-cell RNA sequencing (scRNA-seq) of MSC-GY. GSEA and Scissor analyses were used to find the functional subpopulations of MSCs that promote angiogenesis. The role of functional subpopulations in promoting angiogenesis was verified by detecting the secretory proteins, the ratio of N-CADHERIN+/CD168− subpopulations in MSCs, and the tube formation, migration, and proliferation of HUVECs after treatment with conditional medium (CM) derived from different MSCs. Results We found that umbilical cord-derived MSCs (UC-MSCs) from different donors have varied therapeutic efficacy in MI mice and UC-MSCs with higher therapeutic effectiveness exhibited the most potent pro-angiogenic effects by secreting elevated levels of angiogenesis-related proteins, such as MYDGF, VEGFA, and FGF2. ScRNA-seq of 10,463 UC-MSCs revealed that the N-CADHERIN+/CD168− subpopulation was closely associated with pro-angiogenic effects, and the ratio of this cell subpopulation was positively correlated with the angiogenic potential of MSCs. We also found that the N-CADHERIN+/CD168− subpopulation was the functional subpopulation of MSCs in improving cardiac function of MI mice. Conclusions Our study identified that the N-CADHERIN+/CD168− subpopulation was the functional subpopulation of MSCs in treating MI, which was essential for the development and utilization of MSCs in MI treatment.

Background and objective: The use of mesenchymal stem cells for heart failure treatment has gained increasing interest. However, most studies have relied on a single injection approach, with no research yet confirming the effects of multiple administrations. The present trial aims to investigate the safety and efficacy of multi-intravenous infusion of umbilical cord-mesenchymal stem cells (UC-MSCs) in patients with heart failure and reduced ejection fraction (HFrEF). Methods: The PRIME-HFrEF trial is a single-center, prospective, randomized, triple-blinded, placebo-controlled trial of multi-intravenous infusion of UC-MSCs in HFrEF patients. A total of 40 patients meeting the inclusion criteria for HFrEF were enrolled and randomized 1:1 to the MSC group or the placebo group. Patients enrolled will receive intravenous injections of either UC-MSCs or placebo every 6 weeks for three times. Both groups will be followed up for 12 months. The primary safety endpoint is the incidence of serious adverse events. The primary efficacy endpoint is a change in left ventricular ejection fraction (LVEF) measured by left ventricular opacification (LVO) with contrast echocardiography and magnetic resonance imaging (MRI) at 12 months. The secondary endpoints include a composite of the incidence of death and re-hospitalization caused by heart failure at the 12th month, serum NT-proBNP, growth stimulation expressed gene 2 (ST2), and a change of right ventricular structure and function. Conclusions: The PRIME-HFrEF study is designed to shed new light on multiple UC-MSC administration regimens for heart failure treatment.

Abstract Background Associations between perceived and actual risk of HIV infection and HIV prevention services uptake are inconclusive. This study aimed to evaluate the discrepancy between the perceived and actual HIV risk, and quantify the associations between perceived and actual risk of HIV infection and three HIV prevention services utilization among men who have sex with men (MSM) in Shandong province, China. Methods A cross-sectional study was conducted in Shandong province in June 2021. Participants were eligible if they were born biologically male, aged 18 years or older, had negative or unknown HIV status, and had sex with men in the past year. Participants were recruited online. The discrepancy between their perceived and actual risk of HIV infection was evaluated by calculating the Kappa value. Bayesian model averaging was used to assess the associations between perceived and actual risk of HIV infection and HIV prevention services uptake. Results A total of 1136 MSM were recruited, most of them were 30 years old or younger (59.9%), single (79.5%), with at least college education level (74.7%). Most participants (97.4%) perceived that they had low risk of HIV infection, and 14.1% were assessed with high actual risk. The discrepancy between their perceived and actual risk of HIV infection was evaluated with a Kappa value of 0.076 (P

ObjectiveTo explore the intervention effects of different social media platforms on improving the knowledge of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) diagnosis and treatment among HIV-positive men who have sex with men (MSM). MethodsA total of 288 HIV-positive MSM were recruited at the Shandong Provincial Public Health Clinical Center from October to December 2020, and according to their preference, the MSM were divided into three groups to receive information on the knowledge and practice of HIV/AIDS diagnosis and treatment via short message service (SMS), WeChat, and the combination of WeChat and QQ group in six months. The generalized estimating equation used to analyze and compare the intervention effects of the interventions via different social media on the overall knowledge score of HIV/AIDS diagnosis and treatment among the all and subgroups of the participants. ResultsThe mean age of the participants was 34.67 ± 9.22 years. Six-month follow-up showed that the total score of HIV/AIDS diagnosis and treatment knowledge in the WeChat intervention group was 0.38 points higher than that in the SMS intervention group (P = 0.01), and there was no significant difference between the results of the other intervention groups (P > 0.05); in the subgroup with high school education and below, WeChat intervention (P = 0.018), WeChat and QQ group intervention (P = 0.002) were better than SMS intervention in improving the total score of AIDS diagnosis and treatment knowledge. ConclusionCompared with SMS intervention, WeChat intervention significantly improved the HIV/AIDS diagnosis and treatment knowledge score of HIV-positive MSM, and WeChat can be used as the main media for HIV-positive MSM to popularize HIV/AIDS knowledge in the future.

Abstract Background Mesenchymal stem cells (MSCs) hold a great promise for cell-based therapy in the field of regenerative medicine. In this study, we aimed to evaluate the safety and efficacy of intravenous infusion of human umbilical cord-derived MSCs (HUC-MSCs) in patients with aging frailty. Methods In this randomized, double-blind, placebo-controlled trial, participants diagnosed with aging frailty were randomly assigned to receive intravenous administrations of HUC-MSCs or placebo. All of serious adverse events and AEs were monitored to evaluate the safety of treatment during the 6-month follow-up. The primary efficacy endpoint was alteration of physical component scores (PCS) of SF-36 qualities of life at 6 months. The secondary outcomes including physical performance tests and pro-inflammatory cytokines, were also observed and compared at each follow-up visits. All evaluations were performed at 1 week, 1, 2, 3 and 6 months following the first intravenous infusion of HUC-MSCs. Results In the MSCs group, significant improvements in PCS of SF-36 were observed from first post-treatment visit and sustained throughout the follow-up period, with greater changes compared to the placebo group (p = 0.042). EQ-VAS scores of MSCs group improved significantly at 2 month (p = 0.023) and continued until the end of the 6-month visit (p = 0.002) in comparison to the placebo group. The timed up and go (TUG) physical performance test revealed significant group difference and showed continual enhancements over 6 months (p

Objective This study aimed to compare the effectiveness of instant versus text messaging intervention (TMI) on antiretroviral therapy (ART) adherence among men who have sex with men (MSM) living with HIV. Methods This study was conducted in an infectious disease hospital of Jinan, China from October 2020 to June 2021, using non-randomized concurrent controlled design to compare the effectiveness of instant messaging intervention (IMI) versus TMI. The intervention strategies (health messaging, medication reminder, and peer education) and contents were consistent between the two groups, and the difference was service delivery method and type of information. The primary outcome was the proportion of achieving optimal ART adherence, defined as never missing any doses and delayed any doses more than 1 hour. Results A total of 217 participants (including 72 in TMI group and 145 in IMI group) were included in the study. The proportion of achieving optimal adherence was higher in IMI group than TMI group at the first follow-up (90.2% versus 77.6%, p = 0.021) and second follow-up (86.5% versus 76.6%, p = 0.083). The effect of IMI versus TMI on improving ART adherence was found not to be statistically significant (risk ratio (RR) = 1.93, 95% confidence interval (CI): 0.95–3.94) in complete-case analysis. However, when excluding participants who did not adhere to the interventions, a significant improvement was observed (RR = 2.77, 95%CI: 1.21–6.38). More participants in IMI group expressed highly rated satisfaction to the intervention services than those in TMI group (67.3% versus 50.0%). Conclusions The IMI demonstrated superior efficacy over TMI in improving ART adherence and satisfaction with intervention services. It is suggested that future digital health interventions targeting ART adherence should prioritize instant messaging with multimedia information in areas with Internet access. Trial registration The study was registered at the Chinese Clinical Trial Register (ChiCTR), with number [ChiCTR2000041282].

Background: Efficiently increasing the production of clinical-grade mesenchymal stem cells (MSCs) is crucial for clinical applications. Challenges with the current planar culture methods include scalability issues, labour intensity, concerns related to cell senescence, and heterogeneous responses. This study aimed to establish a large-scale production system for MSC generation. In addition, a comparative analysis of the biological differences between MSCs cultured under various conditions was conducted. Methods and materials: We developed a GMP-grade three-dimensional hypoxic large-scale production (TDHLSP) system for MSCs using self-fabricated glass microcarriers and a multifunctional bioreactor. Different parameters, including cell viability, cell diameter, immunophenotype, morphology, karyotype, and tumourigenicity were assessed in MSCs cultured using different methods. Single-cell RNA sequencing (scRNA-seq) revealed pathways and genes associated with the enhanced functionality of MSCs cultured in three dimensions under hypoxic conditions (3D_Hypo MSCs). Moreover, CD142 knockdown in 3D_Hypo MSCs confirmed its in vitro functions. Results: Inoculating 2 × 108 MSCs into a 2.6 L bioreactor in the TDHLSP system resulted in a final scale of 4.6 × 109 3D_Hypo MSCs by day 10. The 3D_Hypo MSCs retained characteristics of the 2D MSCs, demonstrating their genomic stability and non-tumourigenicity. Interestingly, the subpopulations of 3D_Hypo MSCs exhibited a more uniform distribution and a closer relationship than those of 2D MSCs. The heterogeneity of MSCs was strongly correlated with ‘cell cycle’ and ‘stroma/mesenchyme’, with 3D_Hypo MSCs expressing higher levels of activated stroma genes. Compared to 2D MSCs, 3D_Hypo MSCs demonstrated enhanced capabilities in blood vessel formation, TGF-β1 secretion, and inhibition of BV2 proliferation, with maintenance of Senescence-Associated β-Galactosidase (SA-β-gal) negativity. However, the enhanced functions of 3D_Hypo MSCs decreased upon the downregulation of CD142 expression. Conclusion: The TDHLSP system led to a high overall production of MSCs and promoted uniform distribution of MSC clusters. This cultivation method also enhanced key cellular properties, such as angiogenesis, immunosuppression, and anti-aging. These functionally improved and uniform MSC subpopulations provide a solid basis for the clinical application of stem cell therapies.

Summary: Background: The use of mesenchymal stem cells (MSCs) has recently emerged as a promising new therapeutic strategy for many diseases including perianal fistulizing Crohn’s disease (CD). Whether hUC-MSCs can promote the healing of luminal ulcer in CD has not been studied so far. Methods: The model of TNBS-induced colitis in rats was used to confirm the efficacy of hUC-MSCs in the treatment of CD. Then, seventeen CD patients refractory to or unsuitable for currently available therapies were enrolled and received once submucosal local injection through colonoscopy combined with once intravenous drip on the next day. All patients received a 24-week follow-up. Clinical and laboratory assessments were monitored at baseline, week 4, 8, 12, and 24. Endoscopic evaluations were conducted at baseline and week 12. Mucosal specimens were obtained at the margin of lesions by endoscopy biopsies and used for RNA sequencing. Two hUC-MSCs co-culture systems were established in vitro, one with the mucosa specimens and the other with M1 macrophages induced from THP1. The expressions of genes representing inflammation (TNFα, IL-6, and IL-1β) and intestinal barrier function (ZO1, CLAUDIN1, and CDH1) were tested by RT-PCR. Findings: hUC-MSCs treatment increased body weight and decreased disease activity index (DAI), colon macroscopic damage index (CMDI), and histopathological score (HPS) of rats with TNBS-induced colitis. The results of the clinical study also showed that this mode of hUC-MSCs application was associated with regression of intestinal ulceration. Eight patients (47%) got endoscopic responses (SES-CD improvement of ≥50% from baseline) and three patients (17.65%) got mucosal healing (SES-CD is zero), with a parallel improvement of clinical and laboratory parameters without serious adverse events. RNA sequencing showed hUC-MSCs therapy was associated with an upregulation of transcripts linked to intestinal epithelial barrier integrity and a downregulation of inflammatory signaling pathways in the intestinal mucosa, especially the TNF signaling pathway, IL-17 signaling pathway, and TLR signaling pathway. RNA expression of intestinal epithelial tight junction protein (ZO1, CLAUDIN1, and CDH1), and the RNA expression of major intestinal inflammatory factors in CD (IL-1β, IL-6, and TNFα, p

BackgroundTreatment of heart failure post myocardial infarction (post-MI HF) with mesenchymal stem/stromal cells (MSCs) holds great promise. Nevertheless, 2-dimensional (2D) GMP-grade MSCs from different labs and donor sources have different therapeutic efficacy and still in a low yield. Therefore, it is crucial to increase the production and find novel ways to assess the therapeutic efficacy of MSCs.Materials and methodshUC-MSCs were cultured in 3-dimensional (3D) expansion system for obtaining enough cells for clinical use, named as 3D MSCs. A post-MI HF mouse model was employed to conduct in vivo and in vitro experiments. Single-cell and bulk RNA-seq analyses were performed on 3D MSCs. A total of 125 combination algorithms were leveraged to screen for core ligand genes. Shinyapp and shinycell workflows were used for deploying web-server.Result3D GMP-grade MSCs can significantly and stably reduce the extent of post-MI HF. To understand the stable potential cardioprotective mechanism, scRNA-seq revealed the heterogeneity and division-of-labor mode of 3D MSCs at the cellular level. Specifically, scissor phenotypic analysis identified a reported wound-healing CD142+ MSCs subpopulation that is also associated with cardiac protection ability and CD142- MSCs that is in proliferative state, contributing to the cardioprotective function and self-renewal, respectively. Differential expression analysis was conducted on CD142+ MSCs and CD142- MSCs and the differentially expressed ligand-related model was achieved by employing 125 combination algorithms. The present study developed a machine learning predictive model based on 13 ligands. Further analysis using CellChat demonstrated that CD142+ MSCs have a stronger secretion capacity compared to CD142- MSCs and Flow cytometry sorting of the CD142+ MSCs and qRT-PCR validation confirmed the significant upregulation of these 13 ligand factors in CD142+ MSCs.ConclusionClinical GMP-grade 3D MSCs could serve as a stable cardioprotective cell product. Using scissor analysis on scRNA-seq data, we have clarified the potential functional and proliferative subpopulation, which cooperatively contributed to self-renewal and functional maintenance for 3D MSCs, named as “division of labor” mode of MSCs. Moreover, a ligand model was robustly developed for predicting the secretory efficacy of MSCs. A user-friendly web-server and a predictive model were constructed and available (https://wangxc.shinyapps.io/3D_MSCs/).

Drying is one of the best methods to preserve the quality of fresh fruits and prolong their shelf life. This study focuses on Prunus armeniaca L. cv. ‘Diaogan’ (commonly known as Diaogan apricot) sourced from Xinjiang, China to explore the impact of two natural drying methods (shade drying and open-air drying in the rocky desert) on the drying kinetics, color, textural characteristics, microstructure, chemical properties, and antioxidant capacity of Diaogan apricots. The experimental results indicate that throughout the natural drying process, the time required for open-air drying in the rocky desert was reduced by 26.47% compared to shade drying. The L*, a*, and b* values of the shade- and ventilation-dried Diaogan apricots were higher than those sun-dried in the rocky desert, exhibiting a lower color difference (ΔE) than apricots dried through rocky desert sun drying. Specifically, the ΔE for shade-dried Diaogan apricots was 19.66 ± 0.24. The Diaogan apricots dried in the rocky desert exhibited greater hardness, lower elasticity, stronger adhesiveness, and higher chewiness compared to those dried in the shade, with the hardness, adhesiveness, and chewiness being, respectively, 14.71%, 18.89%, and 35.79% higher. Scanning electron microscopy (SEM) observations revealed that the high temperatures experienced during open-air drying in the rocky desert caused rapid dehydration of the Diaogan apricot’s skin, leading to clogging and crust formation in the flesh pores, along with deformation or tearing of the tissue structure, ultimately resulting in poor rehydration ability. After drying, there was a significant increase in the soluble solids in the Diaogan apricots, whereas titratable acidity, total phenols, ascorbic acid, and antioxidant capacity were significantly decreased (p < 0.05). In summary, the quality of dried Diaogan apricots post-drying is dependent on the natural drying method employed, with shade drying resulting in superior quality of Diaogan apricots compared to open-air drying in the rocky desert. This study offers fundamental data and serves as a theoretical reference for the industrialized production of apricots.

Abstract Background Research on the relationship between disclosure of HIV status to male sexual partners (HIV disclosure) and quality of life (QOL) revealed complex and even contradictory results. The impact of HIV disclosure on various domains of QOL and the mediation effect between them are unclear. The purposes of this study were to explore the impact of HIV disclosure on QOL among men who have sex with men (MSM), and whether HIV treatment self-efficacy mediated these relationships. Methods The data came from a baseline survey on the design of a randomized control trial conducted in Shandong, China. A total of 579 MSM patients were included. SPSS 24.0 was used to conduct independent samples t test, one-way analysis of variance and nonparametric tests and the PROCESS macro was used to conduct mediation analysis. Results Among 579 participants, 16.06% disclosed their HIV infection status to their male sexual partners. The effect of HIV disclosure on QOL was mediated by treatment self-efficacy. Self-efficacy played partial mediating role in social relationships, meaning that HIV disclosure had both direct and indirect effects on this factor. In the overall QOL and domains of physical, psychological, independence, and environment, HIV disclosure had an indirect effect only through self-efficacy and no significant effect on the spirituality domain. Conclusions The results emphasize the importance of HIV disclosure and self-efficacy on the QOL of MSM patients and suggest that health care providers should assist MSM patients in deciding whether to disclose their HIV status during daily medical services.

Abstract Background Consistent and complete adherence is considered an essential requirement for patients on antiretroviral therapy (ART). This study aimed to evaluate the impact of ART duration on ART adherence, identify the trend of complete adherence, and compare the factors associated with ART adherence between short-term and long-term ART group among men who have sex with men (MSM) living with HIV in Jinan of China. Methods MSM living with HIV aged 18 or above and currently on ART were recruited from October to December 2020 using convenience sampling. Univariate and multivariable logistic regressions were used to evaluate the impact of ART duration on adherence and compare factors associated with ART adherence between subgroups. The Mann–Kendall test was used to identify the trend of complete adherence. Results A total of 585 participants were included in analysis, consisting of 352 on short-term ART (ART initiation ≤ 3 years) and 233 on long-term ART (ART initiation > 3 years). Significant difference of complete ART adherence between short-term and long-term ART group was detected (79.8% vs. 69.1%, P = 0.003). Multivariable analysis showed that men with longer ART duration were less likely to report complete ART adherence (AOR = 0.88, 95% CI 0.81–0.95). A descending trend of complete adherence was identified (Z = 1.787, P = 0.037). Alcohol use and lack of medication reminders were barriers to complete adherence for both of the subgroups. Conclusions Sustained efforts to encourage maintaining adherence for a lifetime are necessary, especially for those on long-term ART. Future interventions should be tailored to subgroups with different ART duration and individuals with specific characteristics.

Abstract Background Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSC therapy. This study investigated whether the combination of melatonin and human umbilical cord mesenchymal stem cells (hUC-MSCs) was superior to hUC-MSCs alone in ameliorating high-fat diet and streptozocin (STZ)-induced type II diabetes mellitus (T2DM) in a mouse model. Methods Mice were divided into four groups: normal control (NC) group; T2DM group; hUC-MSCs treatment alone (UCMSC) group and pretreatment of hUC-MSCs with melatonin (UCMSC/Mel) group. Results RNA sequence analysis showed that certain pathways, including the signaling pathway involved in the regulation of cell proliferation signaling pathway, were regulated by melatonin. The blood glucose levels of the mice in the UCMSC and UCMSC/Mel treatment groups were significantly reduced compared with the T2DM group without treatment (P

Despite recent studies, relatively few are known about the diversity of fungal communities in the deep Atlantic Ocean. In this study, we investigated the diversity of fungal communities in 15 different deep-sea sediments from the South Atlantic Ocean with a culture-dependent approach followed by phylogenetic analysis of ITS sequences. A total of 29 fungal strains were isolated from the 15 deep-sea sediments. These strains belong to four fungal genera, including Aspergillus, Cladosporium, Penicillium, and Alternaria. Penicillium, accounting for 44.8% of the total fungal isolates, was a dominant genus. The antiaflatoxigenic activity of these deep-sea fungal isolates was studied. Surprisingly, most of the strains showed moderate to strong antiaflatoxigenic activity. Four isolates, belonging to species of Penicillium polonicum, Penicillium chrysogenum, Aspergillus versicolor, and Cladosporium cladosporioides, could completely inhibit not only the mycelial growth of Aspergillus parasiticus mutant strain NFRI-95, but also the aflatoxin production. To our knowledge, this is the first report to investigate the antiaflatoxigenic activity of culturable deep-sea fungi. Our results provide new insights into the community composition of fungi in the deep South Atlantic Ocean. The high proportion of strains that displayed antiaflatoxigenic activity demonstrates that deep-sea fungi from the Atlantic Ocean are valuable resources for mining bioactive compounds.

Viral infections can alter host transcriptomes by manipulating host splicing machinery. Despite intensive transcriptomic studies on SARS-CoV-2, a systematic analysis of alternative splicing (AS) in severe COVID-19 patients remains largely elusive. Here we integrated proteomic and transcriptomic sequencing data to study AS changes in COVID-19 patients. We discovered that RNA splicing is among the major down-regulated proteomic signatures in COVID-19 patients. The transcriptome analysis showed that SARS-CoV-2 infection induces widespread dysregulation of transcript usage and expression, affecting blood coagulation, neutrophil activation, and cytokine production. Notably, CD74 and LRRFIP1 had increased skipping of an exon in COVID-19 patients that disrupts a functional domain, which correlated with reduced antiviral immunity. Furthermore, the dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity. In summary, our data highlight that a better understanding of the AS landscape may aid in COVID-19 diagnosis and therapy.

Abstract Transplanting functional cells to treat myocardial infarction (MI), a major disease threatening human health, has become the focus of global therapy. However, the efficacy has not been well anticipated, partly due to the lack of microvascular system that supplies nutrients and oxygen. Here, spheroids of early vascular cells (EVCs) derived from human embryonic stem cells (hESCs), rather than single‐cell forms, as transplant “seeds” for reconstructing microvascular networks, are proposed. Firstly, EVCs containing CD34+ vascular progenitor cells are identified, which effectively differentiate into endothelial cells in situ and form vascular networks in extracellular matrix (ECM) hydrogel. Secondly, cardiac microtissues and cardiac patches with well‐organized microvasculature are fabricated by three‐dimensional (3D) co‐culture or bioprinting with EVCs and cardiomyocytes in hydrogel. Notably, in 3D‐bioprinted myocardial models, self‐assembly vascularization of EVC spheroids is found to be significantly superior to EVC single cells. EVC spheroids are also injected into ischemic region of MI mouse models to explore its therapeutic potential. These findings uncover hESCs‐derived EVC spheroids rather than single cells are more accessible for complex vasculature engineering, which is of great potential for cardiac tissue vascular engineering and MI treatment by cell therapy.

Summary: Fetal growth restriction (FGR) increases the risk for impaired cognitive function later in life. However, the precise mechanisms remain elusive. Using dexamethasone-induced FGR and protein restriction-influenced FGR mouse models, we observe learning and memory deficits in adult FGR offspring. FGR induces decreased hippocampal neurogenesis from the early post-natal period to adulthood by reducing the proliferation of neural stem cells (NSCs). We further find a persistent decrease of Tet1 expression in hippocampal NSCs of FGR mice. Mechanistically, Tet1 downregulation results in hypermethylation of the Dll3 and Notch1 promoters and inhibition of Notch signaling, leading to reduced NSC proliferation. Overexpression of Tet1 activates Notch signaling, offsets the decline in neurogenesis, and enhances learning and memory abilities in FGR offspring. Our data indicate that a long-term decrease in Tet1/Notch signaling in hippocampal NSCs contributes to impaired neurogenesis following FGR and could serve as potential targets for the intervention of FGR-related cognitive disorders.

Abundant evidence proves the therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) in the treatment of diabetes mellitus. However, the problems have not been solved that viability of ADMSCs were inconsistent and the cells quickly undergo senescence after in vitro cell culture. In addition, the therapeutic effect of ADMSCs is still not satisfactory. In this study, melatonin (MLT) was added to canine ADMSC culture medium, and the treated cells were used to treat type 2 diabetes mellitus (T2DM). Our research reveals that adding MLT to ADMSC culture medium can promote the viability of ADMSCs. This effect depends on the binding of MLT and MLT receptors, which activates the transforming growth factor β (TGF-β) pathway and then changes the cell cycle of ADMSCs and improves the viability of ADMSCs. Since ADMSCs were found to be used to treat T2DM by anti-inflammatory and anti-endoplasmic reticulum (ER) stress capabilities, our data demonstrate that MLT augment several effects of ADMSCs in remission hyperglycemia, insulin resistance, and liver glycogen metabolism in T2DM patients. This suggest that ADMSCs and MLT-ADMSCs is safe and vabulable for pet clinic.

Summary: Although the functional roles of long noncoding RNAs (lncRNAs) have been increasingly identified, few lncRNAs that control the naïve state of embryonic stem cells (ESCs) are known. Here, we report a naïve-state-associated lncRNA, LincU, which is intrinsically activated by Nanog in mESCs. LincU-deficient mESCs exhibit a primed-like pluripotent state and potentiate the transition from the naïve state to the primed state, whereas ectopic LincU expression maintains mESCs in the naïve state. Mechanistically, we demonstrate that LincU binds and stabilizes the DUSP9 protein, an ERK-specific phosphatase, and then constitutively inhibits the ERK1/2 signaling pathway, which critically contributes to maintenance of the naïve state. Importantly, we reveal the functional role of LincU to be evolutionarily conserved in human. Therefore, our findings unveil LincU as a conserved lncRNA that intrinsically restricts MAPK/ERK activity and maintains the naïve state of ESCs. : Kang and colleagues report a naïve-state-associated long noncoding RNA (LincU), which is directly regulated by Nanog and stabilizes the ERK-specific phosphatase DUSP9 by protecting it from ubiquitin-proteasome mediated degradation to maintain the naïve state of mESCs. Moreover, LincU is functionally conserved in human ESCs. Keywords: naïve state, embryonic stem cells, lincRNA, DUSP9, MAPK signaling

Summary: During reprogramming, telomere re-elongation is important for pluripotency acquisition and ensures the high quality of induced pluripotent stem cells (iPSCs), but the regulatory mechanism remains largely unknown. Our study showed that fully reprogrammed mature iPSCs or mouse embryonic stem cells expressed higher levels of miR-590-3p and miR-590-5p than pre-iPSCs. Ectopic expression of either miR-590-3p or miR-590-5p in pre-iPSCs improved telomere elongation and pluripotency. Activin receptor II A (Acvr2a) is the downstream target and mediates the function of miR-590. Downregulation of Acvr2a promoted telomere elongation and pluripotency. Overexpression of miR-590 or inhibition of ACTIVIN signaling increased telomeric repeat binding factor 1 (Terf1) expression. The p-SMAD2 showed increased binding to the Terf1 promoter in pre-iPSCs compared with mature iPSCs. Downregulation of Terf1 blocked miR-590- or shAcvr2a-mediated promotion of telomere elongation and pluripotency in pre-iPSCs. This study elucidated the role of the miR-590/Acvr2a/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. : In this article, Kang and colleagues elucidate the critical function and regulatory mechanism of the miR-590/Acvr2a/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. These findings not only determined the miR-590/Acvr2a/Terf1 axis on regulating both telomere elongation and pluripotency but also revealed an underlying mechanism pushing forward the maturation of the pre-iPSCs. Keywords: miR-590, Acvr2a, Terf1, iPSCs, pluripotency, telomere

Deployable membrane structures have received wide attention in many engineering applications, such as the military, aerospace, and aviation. Their properties of light weight and high storage ratio meet the requirements for aerospace exactly. In this paper, the wrapping deployment of membrane structures inspired by leaves are simulation-analyzed for prospective improvement. Three leaf-inspired patterns are investigated and discussed from the corresponding paper-craft design principles and deployment process perspectives. The deployment performance evaluation system according to the factors effecting working performance including maximum stress, driving force, maximum strain energy, smoothness index, and maximum folding height is established based on the results of the simulation analysis. Then, a comparison between the three patterns is carried out based on the deployment performance evaluation system. Moreover, it is found that adding creases reduces the folded height but the development performance gets worse. There is a balance between the folding ratio and development performance when the additional creases are added. The results can provide useful suggestions for designing wrapping deployment structures.

Summary: During gastrulation, the neuroectoderm cells form the neural tube and neural crest. The nervous system contains significantly more microRNAs than other tissues, but the role of microRNAs in controlling the differentiation of neuroectodermal cells into neural tube epithelial (NTE) cells and neural crest cells (NCCs) remains unknown. Using embryonic stem cell (ESC) neural differentiation systems, we found that miR-29b was upregulated in NTE cells and downregulated in NCCs. MiR-29b promoted the differentiation of ESCs into NTE cells and inhibited their differentiation into NCCs. Accordingly, the inhibition of miR-29b significantly inhibited the differentiation of NTE cells. A mechanistic study revealed that miR-29b targets DNA methyltransferase 3a (Dnmt3a) to regulate neural differentiation. Moreover, miR-29b mediated the function of Pou3f1, a critical neural transcription factor. Therefore, our study showed that the Pou3f1-miR-29b-Dnmt3a regulatory axis was active at the initial stage of neural differentiation and regulated the determination of cell fate. : In this article, Kang and colleagues demonstrated that miR-29b mediated the function of a critical neural transcription factor Pou3f1 to promote the differentiation of ESCs into NTE cells and inhibit their differentiation into NCCs by targeting Dnmt3a. This study showed that the Pou3f1-miR-29b-Dnmt3a regulatory axis was active at the initial stage of neural differentiation and regulated cell fate determination. Keywords: ESCs, neural tube epithelial cells, neural crest cells, miR-29b, Dnmt3a, Pou3f1

Environmental stresses are increasingly acknowledged as core causes of abnormal neural induction leading to neural tube defects (NTDs). However, the mechanism responsible for environmental stress-triggered neural induction defects remains unknown. Here, we report that a spectrum of environmental stresses, including oxidative stress, starvation, and DNA damage, profoundly activate SIRT1, an NAD+-dependent lysine deacetylase. Both mouse embryos and in vitro differentiated embryonic stem cells (ESCs) demonstrated a negative correlation between the expression of SIRT1 and that of OCT6, a key neural fate inducer. Activated SIRT1 radically deacetylates OCT6, triggers an OCT6 ubiquitination/degradation cascade, and consequently increases the incidence of NTD-like phenotypes in mice or hinders neural induction in both human and mouse ESCs. Together, our results suggest that early exposure to environmental stresses results in the dysregulation of the SIRT1/OCT6 axis and increases the risk of NTDs.

Induced pluripotent stem cells (iPSCs) have great potential for treating age-related diseases, but the genome integrity of iPSCs is critically important. Here, we demonstrate that non-homologous end joining (NHEJ), rather than homologous recombination (HR), is less efficient in iPSCs from old mice than young mice. We further find that Sirt6 is downregulated in iPSCs from old mice. Sirt6 directly binds to Ku80 and facilitates the Ku80/DNA-PKcs interaction, thus promoting DNA-PKcs phosphorylation at residue S2056, leading to efficient NHEJ. Rescue experiments show that introducing a combination of Sirt6 and the Yamanaka factors during reprogramming significantly promotes DNA double-strand break (DSB) repair by activating NHEJ in iPSCs derived from old mice. Thus, our study suggests a strategy to improve the quality of iPSCs derived from old donors by activating NHEJ and stabilizing the genome.

Two structural performance indexes, making use of eigenvalues of stiffness matrix, are presented in the study for the evaluation of element importance in the progressive collapse analysis of space trusses. Both indexes are based on the consensus that the element transferring higher loads in the load path is generally more important in the structural sys­tem. The first index is formulated as change of the smallest stiffness after removal of specific element, and the second in­dex is defined as determinant of the stiffness matrix. Several simple numerical examples are presented to investigate per­formance of the proposed indexes; and finally, a square pyramid space grid system is studied as an illustrative example.

The mechanisms by which microRNAs (miRNAs) affect cell fate decisions remain poorly understood. Herein, we report that miR-200a can suppress the differentiation of mouse embryonic stem (ES) cells into endoderm and mesoderm. Interestingly, miR-200a directly targets growth factor receptor-bound protein 2 (Grb2), which is a key adaptor in the Erk signaling pathway. Furthermore, high levels of miR-200a dramatically decrease Grb2 levels and suppress the appearance of mesoderm and endoderm lineages in embryoid body formation, as well as suppressing the activation of Erk. Finally, Grb2 supplementation significantly rescues the miR-200a-induced layer-formation bias and the Erk suppression. Collectively, our results demonstrate that miR-200a plays critical roles in ES cell lineage commitment by directly regulating Grb2 expression and Erk signaling.

In mammalian germ cells, meiotic commitment requires the expression of Stimulated by retinoic acid gene 8 (Stra8), which is transcriptionally activated by retinoic acid (RA). However, little is known about the epigenetic mechanism by which RA induces Stra8 expression. Utilizing a chromatin immunoprecipitation assay (ChIP), we showed that RA increases histone acetylation at the Stra8 promoter in murine embryonic stem cells (ESCs), a model for germ cell differentiation. Furthermore, we explored whether two coregulators with histone acetyltransferase (HAT) activity, Creb-binding protein (CBP) and p300, are involved in the activation of Stra8. The lentiviral shRNA knockdown of endogenous CBP led to Stra8 repression, while the overexpression of CBP enhanced Stra8 expression at both the mRNA and protein levels. ChIP analysis confirmed that CBP is the crucial coactivator for RA-mediated Stra8 transcription and that it enhances the level of histone acetylation and recruits RNA polymerase II to establish transcriptionally active chromatin. Furthermore, shRNA of p300 enhanced Stra8 expression, and the overexpression of p300 reduced Stra8 expression, independently of its HAT activity. ChIP showed that the knockdown of p300 significantly increased the level of CBP at the Stra8 promoter. These findings demonstrate that CBP and p300 play distinct roles in RA-mediated Stra8 gene transcription.

'General requirements for the production of extracellular vesicles derived from human stem cells' is the first guideline for stem cells derived extracellular vesicles in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the general requirements, process requirements, packaging and labelling requirements and storage requirements for preparing extracellular vesicles derived from human stem cells, which is applicable to the research and production of extracellular vesicles derived from stem cells. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that the publication of this guideline will promote institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardisation of extracellular vesicles derived from human stem cells. [ABSTRACT FROM AUTHOR]

Abstract Background The hypothalamic-pituitary-adrenal axis is thought to play a vital role in glucose homeostasis and diabetes. This study investigated the association between morning serum cortisol and time in range (TIR), including daytime TIR, in type 2 diabetes (T2DM). Methods 310 patients with T2DM had serum cortisol measured at 8 a.m. All participants underwent continuous glucose monitoring (CGM) for three consecutive days, then TIR and glycemic variability (GV) parameters were evaluated. Using 100 g standard steamed bread meal test, blood glucose, C peptide and insulin at different points were collected to assess insulin sensitivity and islet function. Results Patients with higher serum cortisol exhibited lower TIR and TITR (P 0.05). Multiple stepwise regression revealed that cortisol was an independent contributor of TIR, TITR and diurnal TIR, with diurnal TIR of stronger relevance. Conclusions Morning serum cortisol is negatively correlated with TIR, especially diurnal TIR and positively associated with GV parameters. Inappropriate cortisol secretion may have an adverse influence on glucose homeostasis in T2DM.

Abstract Increasing evidence suggests that mitophagy is crucially involved in the progression of polycystic ovary syndrome (PCOS). Exploration of PCOS-specific biomarkers related to mitophagy is expected to provide critical insights into disease pathogenesis. In this study, we employed bioinformatic analyses and machine learning algorithms to determine novel biomarkers for PCOS that may be tied with mitophagy. A grand total of 12 differential expressed mitophagy-related genes (DE‐MRGs) associated with PCOS were identified. TOMM5 and MAP1LC3A among the 12 DE‐MRGs were recognized as potential marker genes by LASSO, RF and SVM‐RFE algorithms. The area under the ROC curve (AUROC) of MAP1LC3A were all greater than 0.8 both in the training set and validation sets. The CIBERSORT analysis indicated a potential association between alterations in the immune microenvironment of PCOS individuals and MAP1LC3A expression. In addition, we found that MAP1LC3A was positively related to the testosterone levels of PCOS patients. Overall, MAP1LC3A was identified as optimal PCOS-specific biomarkers related to mitophagy. Our findings created a diagnostic strength and offered a perspective for investigating the mitophagy process in PCOS.

Background The treatment of idiopathic refractory nephrotic syndrome (IRNS) remains a difficult problem in clinical practice. This study aims to determine the efficacy and safety of combining low-dose glucocorticoids with rituximab in IRNS treatment.Methods This prospective, single-center cohort study enrolled 60 patients who were diagnosed with refractory IRNS with minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) and treated at First Affiliated Hospital of Sun Yat-sen University. All patients received a treatment regimen consisting of rituximab (375 mg/m2/week × 4) and low-dose glucocorticoids.Results 46 complete remissions and 4 partial remissions were observed within 6 months of treatment. Within 12 months of treatment, 48 patients achieved complete remission, and 4 achieved partial remission. The complete remission rate for steroid-dependent/frequently relapsing nephrotic syndrome was significantly higher than that for steroid-resistant nephrotic syndrome (88.24% vs. 33.33%, p

Gynostemma pentaphyllum (Thunb.) Makino (GP), a plant with homology of medicine and food, as a traditional Chinese medicine, possesses promising biological activities in the prevention and treatment of type 2 diabetes mellitus (T2DM). However, the material basis and the mechanism of action of GP in the treatment of T2DM have not been fully elucidated. This study aimed to clarify the active components, potential targets and signaling pathways of GP in treating T2DM. The chemical ingredients of GP were collected by combining UPLC-HRMS analysis and literature research. Network pharmacology revealed that GP had 32 components and 326 potential targets in treating T2DM. The results showed that GP affected T2DM by mediating the insulin resistance signaling pathway, PI3K/Akt signaling pathway and FoxO1 signaling pathway, which had a close relationship with T2DM. Molecular docking results showed that STAT3, PIK3CA, AKT1, EGFR, VEGFA and INSR had high affinity with the active compounds of GP. In vitro, GP extracts obviously increased the glucose uptake and glucose consumption in IR-HepG2 cells. GP extracts increased the levels of PI3K, p-AKT, p-GSK3β and p-FoxO1 and decreased the expression of p-IRS1, p-GS, PEPCK and G6Pase, which indicated that GP could promote glycogen synthesis and inhibit gluconeogenesis by regulating the IRS1/PI3K/Akt signaling pathway. The results demonstrated that GP could improve insulin resistance by promoting glucose uptake and glycogen synthesis and inhibiting gluconeogenesis through regulating the IRS1/PI3K/Akt signaling pathway, which might be a potential alternative therapy for T2DM.

Abstract Background Larval settlement and metamorphosis represent critical events in the life history of marine benthic animals. Myoinhibitory peptide (MIP) plays a pivotal role in larval settlement of marine invertebrates. However, the molecular mechanisms of MIP involved in this process are not well understood. Results In this study, we evaluated the effects of thirteen MIP mature peptides on triggering the larval settlement of Urechis unicinctus (Xenopneusta, Urechidae), and determined that MIP2 was the principal neuropeptide. Transcriptomic analysis was employed to identify differentially expressed genes (DEGs) between the MIP2-treated larvae and normal early-segmentation larvae. Both cAMP and calcium signaling pathways were enriched in the DEGs of the MIP2-treated larvae, and two neuropeptide receptor genes (Spr, Fmrfar) were up-regulated in the MIP2-treated larvae. The activation of the SPR-cAMP pathway by MIP2 was experimentally validated in HEK293T cells. Furthermore, fourteen cilia-related genes, including Tctex1d2, Cfap45, Ift43, Ift74, Ift22, Cav1 and Mns1, etc. exhibited down-regulated expression in the MIP2-treated larvae. Whole-mount in situ hybridization identified two selected ciliary genes, Tctex1d2 and Cfap45, were specially expressed in circumoral ciliary cells of the early-segmentation larvae. Knocking down Tctex1d2 mRNA levels by in vivo RNA interference significantly increased the larval settlement rate. Conclusion Our findings suggest that MIP2 inhibits the function of the cilia-related genes, such as Tctex1d2, through the SPR-cAMP-PKA pathway, thereby inducing larval settlement in U. unicinctus. The study contributes important data to the understanding of neuropeptide regulation in larval settlement.

Abstract Objective This study aims to investigate the effect of diminished ovarian reserve (DOR) on the clinical outcomes and maternal and infant safety of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) procedures in young women aged ≤ 35 years. Methods A retrospective cohort study was performed to analyze the clinical data of 4,203 infertile women aged ≤ 35 years who underwent fresh embryo transfer (ET) in IVF/ICSI cycles. The data were collected from their initial visits to Fujian Maternity and Child Health Hospital between January 2015 and January 2022. Based on their ovarian reserve, the participants were categorized into two groups: DOR group (n = 1,027) and non-DOR group (n = 3,176). A propensity score matching (PSM) method was employed to ensure a relatively balanced distribution of covariates. The primary outcome assessed in this study was the live birth rate, while the secondary observation indicators included rates of high-quality embryo development, blastocyst formation, clinical pregnancy, and miscarriage, along with perinatal complications, neonatal birth weight, and the incidence of low birth weight (LBW). Results The DOR group showed notably lowered rates of blastocyst formation (59.8% vs. 64.1%), embryo implantation (29.8% vs.33.3%), clinical pregnancy (47.9% vs. 53.6%), and live birth (40.6% vs. 45.7%) compared to the non-DOR group (all P 0.05). Conclusion DOR has been found to reduce both clinical pregnancy and live birth rates in young females undergoing fresh ET in IVF/ICSI cycles. However, this reduction does not increase the risk of perinatal complications or LBW of infants through live birth cycles.

Uncertainty quantification is important for making reliable decisions in transportation planning and operations. In the field of short-term traffic condition forecasting, uncertainty quantification methods include primarily distribution-based approaches and nondistributionbased approaches. For the former, the generalized autoregressive conditional heteroscedasticity (GARCH) model has been widely applied to model and quantify traffic condition uncertainty in terms of prediction interval under normality assumption. However, this normality assumption has not been systematically investigated yet. Therefore, this paper attempts to investigate this normality assumption and thereby quantify traffic condition uncertainty, using a method with steps of residual calculation and investigation, normality investigation, distribution estimation, uncertainty quantification, and performance measurement. Using real-world traffic flow data, the distributions of the selected samples are shown to be nonnormal using the Kolmogorov-Smirnov test and normal probability plot. Distribution estimation using nonnormal models shows that the t location-scale distribution and generalized error distribution (GED) can be used to model traffic condition uncertainty. Uncertainty quantification using GARCH under these nonnormal distributions further show that nonnormal models outperform the normal model, with the GARCH model under t location-scale distribution yielding the best performance. Future studies are recommended to promote the investigation into traffic condition uncertainty quantification and application. [ABSTRACT FROM AUTHOR]

Abstract Introduction The Data‐informed Stepped Care (DiSC) study is a cluster‐randomized trial implemented in 24 HIV care clinics in Kenya, aimed at improving retention in care for adolescents and youth living with HIV (AYLHIV). DiSC is a multi‐component intervention that assigns AYLHIV to different intensity (steps) of services according to risk. We used the Framework for Reporting Adaptations and Modifications‐Expanded (FRAME) to characterize provider‐identified adaptations to the implementation of DiSC to optimize uptake and delivery, and determine the influence on implementation outcomes. Methods Between May and December 2022, we conducted continuous quality improvement (CQI) meetings with providers to optimize DiSC implementation at 12 intervention sites. The meetings were guided by plan‐do‐study‐act processes to identify challenges during early phase implementation and propose targeted adaptations. Meetings were audio‐recorded and analysed using FRAME to categorize the level, context and content of planned adaptations and determine if adaptations were fidelity consistent. Providers completed surveys to quantify perceptions of DiSC acceptability, appropriateness and feasibility. Mixed effects linear regression models were used to evaluate these implementation outcomes over time. Results Providers participated in eight CQI meetings per facility over a 6‐month period. A total of 65 adaptations were included in the analysis. The majority focused on optimizing the integration of DiSC within the clinic (83%, n = 54), and consisted of improving documentation, addressing scheduling challenges and improving clinic workflow. Primary reasons for adaptation were to align delivery with AYLHIV needs and preferences and to increase reach among AYLHIV: with reminder calls to AYLHIV, collaborating with schools to ensure AYLHIV attended clinic appointments and addressing transportation challenges. All adaptations to optimize DiSC implementation were fidelity‐consistent. Provider perceptions of implementation were consistently high throughout the process, and on average, slightly improved each month for intervention acceptability (β = 0.011, 95% CI: 0.002, 0.020, p = 0.016), appropriateness (β = 0.012, 95% CI: 0.007, 0.027, p

Huangjinya has recently seen widespread adoption in key tea-producing areas of China, celebrated for its unique varietal traits. Its leaves are also used to produce black tea with distinctive sensory characteristics. The fragrance-enhancing (EF) process is essential in crafting Huangjinya black tea (HJYBT) and is significant in flavor development. However, the impact of EF on non-volatile metabolites (NVMs), volatile metabolites (VMs), and their interactions remains poorly understood. This study aims to investigate how EF temperatures (60 °C, 70 °C, 80 °C, 90 °C, and 110 °C) influence HJYBT flavor transformation. Quantitative descriptive analysis revealed that EF improved the color, aroma, and appearance of tea leaves. Moreover, after an EF temperature of 80 °C, the HJYBT exhibited lower bitterness and astringency, whereas floral, sweet, and fruity aromas became stronger. However, when EF temperatures exceeded 90 °C, a pronounced burnt aroma developed, with HJYBT at 100 °C exhibiting caramel and roasted notes. Partial least squares discriminant analysis indicated that geraniol and linalool contribute to floral and fruity aromas, while 2-ethyl-6-methyl-pyrazine, furfural, and myrcene are key volatiles for caramel and roast aromas. Heptanal, methyl salicylate, α-citral, 1-hexanol, and (E)-3-hexen-1-ol were found to modify the green and grassy odor. Overall, HJYBT treated at 80 °C EF exhibited the highest umami, sweetness, floral and fruity aromas, and overall taste, exhibiting the least astringency, bitterness, and green and grassy notes. These results provide a significant theoretical basis for enhancing HJYBT quality and selecting the optimal EF method.

Type 2 diabetes mellitus is a chronic metabolic disease characterized by insulin resistance, with high morbidity and mortality worldwide. Due to the tightly intertwined connection between the insulin resistance pathway and the PI3K/AKT signaling pathway, regulating the PI3K/AKT pathway and its associated targets is essential for hypoglycemia and the prevention of type 2 diabetes mellitus. In recent years, metabolites isolated from traditional Chinese medicine has received more attention and acceptance for its superior bioactivity, high safety, and fewer side effects. Meanwhile, numerous in vivo and in vitro studies have revealed that the metabolites present in traditional Chinese medicine possess better bioactivities in regulating the balance of glucose metabolism, ameliorating insulin resistance, and preventing type 2 diabetes mellitus via the PI3K/AKT signaling pathway. In this article, we reviewed the literature related to the metabolites of traditional Chinese medicine improving IR and possessing therapeutic potential for type 2 diabetes mellitus by targeting the PI3K/AKT signaling pathway, focusing on the hypoglycemic mechanism of the metabolites of traditional Chinese medicine in type 2 diabetes mellitus and elaborating on the significant role of the PI3K/AKT signaling pathway in type 2 diabetes mellitus. In order to provide reference for clinical prevention and treatment of type 2 diabetes mellitus.

This study aimed to investigate the role of mitochondrial-related protein Mfn2 in polycystic ovary syndrome (PCOS) and its impact on oocyte development. The pathological features of PCOS model mice were confirmed by hematoxylin–eosin staining and immunohistochemistry. The expression of Mfn2 and mitochondrial-related proteins in PCOS oocytes and granulosa cells was detected by qRT-PCR and Western blot. Mitochondrial quantity was measured by Mito-Tracker staining, and the structure of mitochondria-associated ER membranes (MAMs) was observed by transmission electron microscopy. The results showed that Mfn2 was significantly downregulated in PCOS oocytes and granulosa cells, and its expression was inhibited in oocytes at different developmental stages. Moreover, the structure of MAMs was also disrupted. Downregulation of Mfn2 expression led to a reduction in mitochondrial quantity in oocytes and granulosa cells, as well as disruption of MAM structure, while overexpression of Mfn2 had the opposite effect. In conclusion, this study indicates that Mfn2 affects the development of PCOS oocytes by regulating MAMs and may be involved in maintaining the stability of MAM structure and function, thereby affecting mitochondrial quantity and function. These findings provide new insights into the pathogenesis and treatment of PCOS.

Abstract Purpose To construct and validate a nomogram model for predicting clinical pregnancy in individuals with endometriosis undergoing fersh embryo transfer (ET). Methods A retrospective analysis was conducted on 1630 individuals with endometriosis who underwent in vitro fertilization (IVF) with fresh embryo transfer at the Reproductive Medicine Center of Fujian Maternity and Child Health Hospital from January 2018 to January 2022. The research population was sorted into two groups through random sampling, namely, the model group (n = 1141) and the validation group (n = 489), with a ratio of 7:3. Univariate analysis was utilized to determine the influencing factors for clinical pregnancy in the model group. The LASSO algorithm was utilized to select the optimal matching factors, which were then included in a multifactorial forward stepwise logistic regression to determine independent influencing factors and develop a nomogram. The discrimination, accuracy, and clinical efficacy of the prediction model were analyzed utilizing the receiver operating characteristic (ROC) curve, calibration curve, and clinical decision curve. Results Through multivariate-logistic-regression analysis, these factors were identified as independent influencing factors for the clinical pregnancy in endometriosis patients undergoing fresh embryo transfer: female age (OR = 0.933, 95% CI = 0.902–0.965, P 0.05). The clinical decision curve demonstrated that both the model and the validation groups achieved maximum net benefit at threshold probability values of 0.08–0.96 and 0.16–0.96, indicating good clinical efficacy within this range of threshold probabilities. Conclusion Female age, ASRM stage, postoperative to IVF duration, stimulation protocol, AFC, AMH, number of oocytes retrieved, number of high-quality cleavage embryos and number of transferred embryos are independent influencing factors for the clinical pregnancy rate in individuals with endometriosis receiving fresh embryo transfer. The nomogram model based on these factors demonstrates good clinical predictive value and efficacy, providing a basis for clinical prognosis, intervention, and individualized medical treatment planning.