The novel molecular mechanism of pulmonary fibrosis: insight into lipid metabolism from reanalysis of single-cell RNA-seq databases.

Pulmonary fibrosis (PF) is a severe pulmonary disease with limited available therapeutic choices. Recent evidence increasingly points to abnormal lipid metabolism as a critical factor in PF pathogenesis. Our latest research identifies the dysregulation of low-density lipoprotein (LDL) is a new risk factor for PF, contributing to alveolar epithelial and endothelial cell damage, and fibroblast activation. In this study, we first integrative summarize the published literature about lipid metabolite changes found in PF, including phospholipids, glycolipids, steroids, fatty acids, triglycerides, and lipoproteins. We then reanalyze two single-cell RNA-sequencing (scRNA-seq) datasets of PF, and the corresponding lipid metabolomic genes responsible for these lipids' biosynthesis, catabolism, transport, and modification processes are uncovered. Intriguingly, we found that macrophage is the most active cell type in lipid metabolism, with almost all lipid metabolic genes being altered in macrophages of PF. In type 2 alveolar epithelial cells, lipid metabolic differentially expressed genes (DEGs) are primarily associated with the cytidine diphosphate diacylglycerol pathway, cholesterol metabolism, and triglyceride synthesis. Endothelial cells are partly responsible for sphingomyelin, phosphatidylcholine, and phosphatidylethanolamines reprogramming as their metabolic genes are dysregulated in PF. Fibroblasts may contribute to abnormal cholesterol, phosphatidylcholine, and phosphatidylethanolamine metabolism in PF. Therefore, the reprogrammed lipid profiles in PF may be attributed to the aberrant expression of lipid metabolic genes in different cell types. Taken together, these insights underscore the potential of targeting lipid metabolism in developing innovative therapeutic strategies, potentially leading to extended overall survival in individuals affected by PF.

The Impact of Parental Preconception Body Mass Index on the Outcomes of in vitro Fertilization-Embryo Transfer and Newborns' Outcomes.

Objective: Associations between parental pre-pregnancy BMI in IVF/ICSI fresh embryo transfer cycles and neonatal outcomes were investigated through a retrospective analysis. Methods: A retrospective analysis of Couples who underwent IVF/ICSI fresh embryo transfer 1340 cycles from January 2019 to December 2021 was conducted in the Department of Reproductive Medicine of our hospital. Based on the preconception BMI of parents, they were divided into four groups: Group A (both father and mother with BMI < 25 kg/m²), Group B (father with BMI < 25 kg/m² and mother with BMI ≥ 25 kg/m²), Group C (father with BMI ≥ 25 kg/m² and mother with BMI < 25 kg/m²), and Group D (both father and mother with BMI ≥ 25 kg/m²). The differences in baseline characteristics, fertilization and embryo development, pregnancy outcomes, and neonatal outcomes were compared among the groups. Results: In the IVF cycles, Group A had a higher rate of normal fertilization compared to three other groups, Group A is significantly higher than Group D, with statistical significance (P < .05). In the ICSI cycles, there were no significant differences among the four groups regarding normal fertilization rate, day 3 high-quality embryo rate, blastocyst formation rate, and high blastocyst rate. Univariate and multivariate analysis results showed no significant differences in clinical pregnancy and live birth rates among the four groups. However, Group D had a significantly higher rate of preterm birth than other three groups, with statistical significance (P < .05). Conclusion: To achieve better clinical outcomes and neonatal outcomes, overweight or obese couples should lose weight before undergoing IVF/ICSI treatment.

Bibliometric and Visual Analysis of the Research Status and Knowledge Structure of Assisted Reproductive Therapy for Patients with Premature Ovarian Insufficiency.

Objective: A large proportion of patients undergoing assisted reproductive therapy (ART) suffer from premature ovarian insufficiency (POI). The knowledge structure, research hotspots, and research trends related to ART for patients with POI are still unclear and have not been systematically summarized. We aimed to analyze the research status of ART for patients with POI and deeply explore its knowledge structure and research trends. Our findings may provide treatment recommendations for clinicians and guidance for researchers in further research. Methods: The PubMed database for publications on ART for patients with POI was searched. The Bibliographic Item Co-occurrence Matrix Builder (BICOMB) obtained the Co-word matrix and co-occurrence matrix. The H-index method was used to extract high-frequency main Medical Subject Headings (MeSH) terms/subheadings. Then we used software such as graphical clustering toolkit (gCluto), Microsoft Excel, Ucinet and NetDraw to carry out the biclustering analysis, strategic diagram analysis and social network analysis of the major MeSH terms/subheadings. Results: The high-frequency major MeSH terms/subheadings were analyzed by biclustering, strategic diagram, and social network analyses. A total of 431 articles from 1983 to 2023 were retrieved. Analysis showed that a total of 176 journals published relevant papers, including FERTILITY AND STERILITY, ranking first. In addition, we extracted 20 high-frequency major MeSH terms/subheadings. We grouped them into five categories: cryopreservation of oocyte and ovarian tissue, oocyte donation, in vitro activation (IVA) of primordial follicles, overview of therapy for patients with POI, therapy of iatrogenic POI. Within these five categories, there were 4, 4, 3, 4, and 5 major MeSH terms/subheadings, respectively. The major MeSH terms/subheadings were evenly distributed, and no particular group had a particular central tendency. Conclusion: The therapy of Iatrogenic POI is in the core position of research and is becoming increasingly mature. Oocyte donation and IVA of primordial follicles are the trends of future research. This study is helpful to understand the current research status, knowledge structure, and research trends of ART for patients with POI, and provide reference for improving ART for patients with POI in the future. Our study may guide clinicians to apply more established research to treat patients, which may lead to better treatment outcomes for patients. At the same time, we also suggest that researchers can conduct research in the field of future research trends, which may lead to greater research results.

Evaluation of allylestrenol for clinical pregnancies in patients treated with assisted reproductive techniques: a retrospective, propensity score matched, observational study.

BACKGROUND: Allylestrenol is an oral progestogen being increasingly used for luteal phase support in assisted reproductive techniques. However, evidence of the clinical efficacy of allylestrenol in luteal phase support is lacking. Dydrogesterone is a representative drug used for luteal phase support, the efficacy of which has been clinically confirmed. As such, we aimed to compare the effects of allylestrenol with the standard dydrogesterone on clinical pregnancy rates and pregnancy outcomes. METHODS: This retrospective study included 3375 assisted reproductive technique cycles using either allylestrenol or dydrogesterone between January 2015 and March 2020. Patients using either allylestrenol or dydrogesterone were matched in a 1:1 ratio using propensity scores. The primary outcomes were clinical pregnancy rate and pregnancy outcomes. RESULTS: No significant difference was found in the clinical pregnancy rate (53.5% vs. 53.2%, P = 0.928) and pregnancy outcomes (all P > 0.05) between allylestrenol and dydrogesterone. Compared with dydrogesterone, the use of allylestrenol significantly reduced the rate of biochemical pregnancies (6.4% vs. 11.8%, P < 0.001) and multiple gestation rate (16.8% vs. 26.3%, P = 0.001). Moreover, endometrial thickness, morphology, and blood flow were significantly improved by allylestrenol treatment (all P < 0.05). CONCLUSIONS: Allylestrenol exhibited similar effects on clinical pregnancy rates and pregnancy outcomes as dydrogesterone. Moreover, allylestrenol can significantly reduce the biochemical pregnancy rate and improve the endometrial receptivity.

Predictive value of 3D ultrasound assessment of endometrial receptivity for PGD/PGS for transfer pregnancy outcome.

OBJECTIVE: To investigate the predictive value of three-dimensional ultrasound assessment of endometrial receptivity in PGD/PGS transplantation patients on pregnancy outcome. METHODS: 280 patients undergoing PGD/PGS transplantation were enrolled and divided into group A and group B according to the patients' pregnancy outcomes. The general conditions, endometrial receptivity indexes of the two groups were compared. Multifactorial logistic regression analysis was used to determine the factors influencing pregnancy outcome in PGD/PGS transplant patients. ROC curves were plotted to analyze the predictive value of 3D ultrasound parameters on pregnancy outcome. The results of the study were validated with patients who underwent FET transplantation, and the patients in the validation group were treated with the same 3D ultrasound examination method and treatment plan as the observation group. RESULTS: The differences in basic situations between two groups were not statistically significant (P > 0.05). The percentage of endometrial thickness, endometrial blood flow, and endometrial blood flow classification type II + II were higher in group A than in group B (P < 0.05). Multifactorial logistic regression analysis showed that endometrial thickness, endometrial blood flow and endometrial blood flow classification were influencing factors of pregnancy outcome in PGD/PGS patients. The sensitivity of predicting pregnancy outcome based on the results of transcatheter 3D ultrasound was 91.18%, the specificity was 82.35%, and the accuracy was 90.00%, which has a high predictive value. CONCLUSION: 3D ultrasound can predict pregnancy outcome by assessing the endometrial receptivity of PGD/PGS transplantation, in which endometrial thickness and endometrial blood flow have a good predictive value.

The therapeutic effects of rFSH versus uFSH/uHMG on ovarian stimulation in women undergoing assisted reproductive technology: a meta-analysis of randomized controlled trials.

PURPOSE: This systematic review and meta-analysis aimed to compare the therapeutic effects of rFSH versus uFSH/uHMG on ovarian stimulation in women undergoing assisted reproductive technology. METHODS: The databases of PubMed, Embase, and the Cochrane Library were systematically searched to retrieve data on eligible trials from inception until July 2022. The relative risks (RRs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were applied to assess categorical and continuous outcomes, and the pooled results were calculated using the random-effects model. Sensitivity, subgroup, and publication bias analyses were also performed. RESULTS: Forty-eight trials that enrolled 10,127 women were included in this quantitative meta-analysis. There were no significant differences between rFSH and uFSH/uHMG in the clinical pregnancy rate (RR: 1.01; 95% CI 0.95-1.07; P = 0.760), live birth rate (RR: 0.98; 95% CI 0.91-1.06; P = 0.665), multiple pregnancy rate (RR: 0.92; 95% CI 0.77-1.09; P = 0.320), miscarriage rate (RR: 1.17; 95% CI 0.94-1.46; P = 0.151), and the incidence of ovarian hyperstimulation syndrome (RR: 1.25; 95% CI 0.91-1.70; P = 0.164). In addition, the administration of rFSH was associated with a higher number of oocyte retrieval compared with that of uFSH/uHMG (WMD: 0.61; 95% CI 0.03-1.20; P = 0.038), while no significant differences were found between rFSH and uFSH/uHMG in the dosage of gonadotrophin (WMD: 14.80; 95% CI - 136.97 to 166.57; P = 0.848) and the duration of ovarian stimulation (WMD: - 0.26; 95% CI - 0.62 to 0.10; P = 0.152). Thus, the exploratory analyses revealed several potential differences in the effects of rFSH versus uFSH/uHMG on ovarian stimulation. CONCLUSION: The administration of rFSH significantly increased the number of oocytes retrieved, whereas there were no significant differences between the efficacies of rFSH and uFSH/uHMG for pregnancy outcomes.

[Clinical efficacy of Xuanju compound capsule combined with urofollitropin in the treatment of patients with idiopathic oligoasthenozoospermia].

OBJECTIVE: To evaluate the therapeutic effects of Xuanju compound capsule combined with urofollitropin (uFSH) in the treatment of idiopathic oligoasthenozoospermia. METHODS: From June 2022 to June 2023, patients with idiopathic oligoastheospermia were enrolled in this study, and divided into trail group (Xuanju compound capsule combined with urofollitropin tablets, n=53) and control group (urofollitropin tablets, n=61) according to the difference in treatment. Treatment methods: Xuanju compound capsule, 3 pills, three times a day; Urofollitropin, 75IU, one times three day. The curses of treatments for control group and trail group is 12 weeks. In order to evaluate the therapeutic effects of control group and trial group, semen volume, sperm concentration, progressive sperm ratio (PR), peripheral serum sex hormone, liver functions were analyzed before and after treatment for two times. RESULTS: Compared with the baseline, the semen volume and liver function were not significantly changed after the treatment in control group and trial group. However, sperm concentration, PR, testosterone (T) levels, follicle stimulating hormone (FSH) levels, and luteinizing hormone (LH) levels were significantly unregulated after the treatment in control group and trial group. More importantly, compared to control group, sperm concentration, PR, T leves, FSH levels, LH levels, and T/E2 ratio of trial group were further enhanced after the treatment, which were statistically significant (P < 0.05). CONCLUSIONS: Xuanju compound capsule combined with urofollitropin tablets could significantly improve the semen quality, up-regulate the testosterone levels and T/E2 ratio in patients with idiopathic oligoasthenozoospermia.

PGT-A: The biology and hidden failures of randomized control trials.

OBJECTIVE: Preimplantation Genetic Testing - Aneuploidy (PGT-A) for embryo selection has undergone significant advancements in the last 2 decades and yet many studies still fail to demonstrate any clinical benefits over traditional embryo morphology selection (Mo-S). To understand this conundrum, we performed a multi-center clinical study of PGT-A patients, where Mo-S and euploid selection (Eu-S) outcomes were directly compared. METHOD: All suitable blastocysts were biopsied and analyzed for chromosome copy number. Outcomes (positive beta hCG, implantation, ongoing pregnancy, and live birth rates) for Eu-S were compared to Mo-S using single embryo transfers. RESULTS: Compared to Eu-S embryos, Mo-S embryos resulted in significant reduction of outcomes for positive beta hCG (p = 0.0005), implantation (p = 0.0008), ongoing pregnancy (p = 0.0046), livebirth (p = 0.0112), babies per transfer (p = 0.0112), and babies per embryo transferred (p = 0.0112). Morphology selection resulted in patients of all age groups having non-euploid embryos chosen for transfer. Post-hoc evaluation of individual clinic performances showed variable transfer outcomes that could potentially confound the true benefits of PGT-A. CONCLUSION: Embryo chromosome status is central to improved embryo transfer outcomes and sole reliance on current morphology-based selection practices, without Eu-S, will always compromise outcomes. Often overlooked but a major effector of successful PGT-A outcomes are individual clinic performances.

Nomogram prediction for the prediction of clinical pregnancy in Freeze-thawed Embryo Transfer.

BACKGROUND: This study aimed to identify multiple endometrial receptivity related factors by applying non-invasive, repeatable multimodal ultrasound methods. Combined with basic clinical data, we further established a practical prediction model for early clinical outcomes in Freeze-thawed Embryo Transfer (FET). METHODS: Retrospective analysis of clinical data of infertility patients undergoing FET cycle in our Center from January 2017 to September 2019. Receiver operating characteristic (ROC) curve and decision curve analyses were performed by 500 bootstrap resamplings to assess the determination and clinical value of the nomogram, respectively. RESULTS: A total of 2457 FET cycles were included. We developed simple nomograms that predict the early clinical outcomes in FET cycles by using the parameters of age, BMI, type and number of embryos transferred, endometrial thickness, FI, RI, PI and number of endometrial and sub-endometrial blood flow. In the training cohort, the area under the ROC curve (AUC) showed statistical accuracy (AUC = 0.698), and similar results were shown in the subsequent validation cohort (AUC = 0.699). Decision curve analysis demonstrated the clinical value of this nomogram. CONCLUSIONS: Our nomogram can predict clinical outcomes and it can be used as a simple, affordable and widely implementable tool to provide guidance and treatment recommendations for FET patients.

IVF embryo choices and pregnancy outcomes.

OBJECTIVE: Investigate the chromosome status and transfer outcomes of embryos selected using routine "best morphology" IVF practices. METHOD: A prospective multi-center, non-selection cohort study involving patients undertaking IVF treatment. Study entry conditions were blastocyst biopsy, >1 embryo with chromosome analysis and frozen transfer of the best morphology embryo. Primary analyses were ßhCG positive, implantation, ongoing pregnancy and birth rates and pregnancy-stage progression failures. RESULTS: After transfer, embryo chromosome status was assigned and outcomes divided into two primary groups - euploids (n = 135) and aneuploids (n = 53). Compared to euploid embryo transfers, aneuploid embryos had significantly lower primary outcomes (+ßhCG: 67% vs. 30%, p < 0.0001; IR: 56% vs. 19%, p < 0.0001; ongoing week 12: 51% vs. 9%, p < 0.0001; and livebirths: 50% vs. 8%, p < 0.0001, respectively). Transfers were further subdivided into smaller groups according to their main chromosomal feature. Stage analysis showed higher failure rates for aneuploids to initiate a pregnancy (p < 0.0001), higher subclinical miscarriage rate (p = 0.0402) and higher clinical miscarriage rate (p = 0.0038). CONCLUSION: Routine morphology-based embryo selection resulted in a high euploid selection rate but a significant number of aneuploid embryos were still inadvertently selected for transfer (28%) with the subsequent high failure rates for pregnancy initiation and progression having implications for appropriate patient management.

A modified single-armed microsurgical vasoepididymostomy for epididymal obstructive azoospermia: intraoperative choice and postoperative consideration.

BACKGROUND: To evaluate the clinical outcomes and the duration required for the sperm to return to the ejaculate after a modified single-armed 2-suture longitudinal intussusception vasoepididymostomy (SA-LIVE). METHODS: From March 2015 to December 2018, 134 patients with epididymal obstruction azoospermia underwent the modified single-armed vasoepididymostomy at Shanghai General Hospital. The outcomes and clinical findings were documented and evaluated. The mean follow-up period was 17 (range: 3-36) months. RESULTS: Patency was assessed by the return of sperm in the ejaculate. The overall patency rate was 55.2%, and the patency rates were 58.9, 40.7, 36.4, and 58.9% for bilateral surgery, unilateral surgery, proximal anastomosis, and distal anastomosis, respectively. The average time to achieve patency was 4.11 ± 2.74 months. In the first 6 months, 87.8% (65/74) patency patients reported sperm in the ejaculate. The overall pregnancy rate was 40.9% (29/66) at the follow-up of 3-36 months, and the natural pregnancy rate was 30.3% (20/66). The natural pregnancy rate was 32.1% post-bilateral surgery and 33.3% for the site of distal anastomosis; surprisingly, it was 0% for the site of proximal anastomosis. CONCLUSION: Modified SA-LIVE is safe and may achieve favorable patency and pregnancy rates. When double-armed sutures are not accessible, single-armed may be preferable. The expected patency time was within 1 year. Moreover, because of the low natural pregnancy rate for proximal anastomosis, sperm banking is preferred to SA-LIVE.

[Internal quality control products for computer-assisted sperm analysis: Research and application].

OBJECTIVE: To investigate the application of the self-made semen quality control (QC) product in internal QC of computer-assisted sperm analysis (CASA). METHODS: CASA was calibrated with high- and low-concentration commercially available semen QC product and meanwhile 15 samples of self-made mixed semen QC product were placed in 75 cryotubes containing liquid nitrogen, followed by CASA of the concentration, motility, curvilinear velocity (VCL), straight line velocity (VSL), average path velocity (VAP), linearity (LIN), wobble (WOB) and straightness (STR) of the sperm using standard procedures and 50 days of continuous monitoring. The Makler counting plate was used to measure the concentration and motility of the self-made sperm. RESULTS: The coefficients of variation (CV) of the commercially available semen QC product at high and low concentrations were 6.18% and 7.85%, respectively. CASA showed that the concentration of the self-made QC product was (25.97 ± 1.41) ×106/ml, with a CV of 5.42%, and the sperm motility, VCL, VSL, VAP, LIN, WOB and STR were (22.15 ± 1.75)% (CV = 7.9%), (59.18 ± 2.05) µm/s (CV = 3.46%), (26.79 ± 1.2) µm/s (CV = 4.48%), (34.98 ± 1.4) µm/s (CV = 4.01%), 46.81 ± 1.55 (CV = 3.3%), 60.52 ± 1.3 (CV = 2.15%) and 76.46 ± 1.98 (CV = 2.59%), respectively. The concentration and motility of the self-made sperm detected with the Makler counting plate were (34.39 ± 2.37) ×106/ml (CV = 6.89%) and (38.04 ± 1.69)% (CV = 4.44%), respectively. Levey-Jennings QC charts were plotted for the indicators using the means and standard deviation. CONCLUSIONS: The self-made internal QC product by liquid nitrogen cryopreservation is feasible and effective for monitoring the accuracy and precision of CASA-derived sperm concentration and motion parameters, and it has a smaller CV than the commercially available QC product in measuring sperm concentration.

Analysis of research trends (2014-2023) on oxidative stress and male fertility based on bibliometrics and knowledge graphs.

Background: Oxidative stress (OS) is considered one of the major factors affecting male fertility, and research in this field has seen constant growth year by year. Currently, around 700 relevant papers are published each year, with a trend of further growth. Therefore, this study systematically summarizes the literature published in the last decade from a bibliometric perspective, revealing the dynamic development of the field, identifying research hotspots, analyzing future trends, and providing reference for further research. Methods: Relevant literature on oxidative stress and male fertility was retrieved from the Web of Science Core Collection (WoSCC) database, covering the timespan from 2014 to 2023 and including two types, articles and reviews. CiteSpace and VOSviewer were used for bibliometric analysis, including cluster analysis, co-occurrence analysis, co-citation analysis, and burst analysis of countries/regions, institutions, journals, authors, references, and keywords. Results: This paper studied a total of 5,301 papers involving 107 countries/regions, with China having the highest number of publications (898 papers) and the United States having the highest centrality (0.62). Burst analysis of journal citations revealed the emergence of many new journals (e.g., Antioxidants-Basel, Front Endocrinol) after 2021, indicating continuous expansion and development in this field. Cluster analysis of co-cited references and co-occurring keywords divided the research into areas such as oxidative stress and male infertility, oxidative stress level detection, and antioxidants. The keywords associated with research hotspots shifted from oxidative stress detection, sperm DNA damage, apoptosis, and redox potential to DNA methylation, embryonic development, infection, polyunsaturated fatty acids, and antioxidants. Conclusion: Bibliometric methods provide an intuitive reflection of the development process in the field of oxidative stress and male fertility, as well as the analysis of research hotspots in different periods. Research on oxidative stress and embryonic development, as well as antioxidant health management, may become hotspots in future research.

Associations of dietary selenium intake with the risk of chronic diseases and mortality in US adults.

Objective: Selenium is an essential micronutrient and a type of dietary antioxidant. This study aimed to investigate the associations of dietary selenium intake with the risk of human chronic disease [cardiovascular disease (CVD), diabetes mellitus (DM), and cancer] and mortality among US general adults. Methods: The dietary and demographic data in this study were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Death outcomes were determined by associating with the National Death Index (NDI) records as of December 31, 2019. Logistic regression analyses were used to investigate the relationship of selenium intake with the risk of CVD, DM, and cancer. The effect of dietary selenium on all-cause and disease-specific mortality was estimated with restricted cubic spline (RCS) curves based on the univariate and multivariate Cox proportional hazard models. Results: Among the 25,801 participants, dietary selenium intake was divided into quintiles (Q1-Q5). After covariate adjustment, the results showed that the participants with higher quintiles (Q4 and Q5) of selenium intake tended to have a low risk of CVD (OR = 0.97, 95% CI: 0.96, 0.99; OR = 0.98, 95% CI: 0.97, 1.00, respectively). Moreover, the RCS curves showed a significant nonlinear association between selenium intake and the risk of all-cause (with a HR of 0.82, 95% CI: 0.68, 0.99) and DM-specific mortality (with the lowest HR of 0.30; 95% CI, 0.12-0.75). Furthermore, we conducted a subgroup analysis and found a negative correlation between the highest quartile of selenium intake and all-cause mortality among participants aged 50 and above (HR = 0.75, 95% CI: 0.60-0.93, p = 0.009). Conclusion: Our results indicated that a moderate dietary selenium supplement decreased the risk of CVD and displayed a nonlinear trend in association with the risk of all-cause and DM-specific mortality among US adults. In addition, we found that participants aged 50 and older may benefit from higher selenium intake. However, these findings still need to be confirmed through further mechanism exploration.

Effects of flaxseed oil supplementation on metaphase II oocyte rates in IVF cycles with decreased ovarian reserve: a randomized controlled trial.

Background: This study was designed to explore the effects of flaxseed oil on the metaphase II (MII) oocyte rates in women with decreased ovarian reserve (DOR). Methods: The women with DOR were divided into a study group (n = 108, flaxseed oil treatment) and a control group (n = 110, no treatment). All patients were treated with assisted reproductive technology (ART). Subsequently, the ART stimulation cycle parameters, embryo transfer (ET) results, and clinical reproductive outcomes were recorded. The influencing factors affecting the MII oocyte rate were analyzed using univariate analysis and multivariate analysis. Results: Flaxseed oil reduced the recombinant human follicle-stimulating hormone (r-hFSH) dosage and stimulation time and increased the peak estradiol (E2) concentration in DOR women during ART treatment. The MII oocyte rate, fertilization rate, cleavage rate, high-quality embryo rate, and blastocyst formation rate were increased after flaxseed oil intervention. The embryo implantation rate of the study group was higher than that of the control group (p = 0.05). Additionally, the female age [odds ratio (OR): 0.609, 95% confidence interval (CI): 0.52-0.72, p < 0.01] was the hindering factor of MII oocyte rate, while anti-Müllerian hormone (AMH; OR: 100, 95% CI: 20.31-495, p < 0.01), peak E2 concentration (OR: 1.00, 95% CI: 1.00-1.00, p = 0.01), and the intake of flaxseed oil (OR: 2.51, 95% CI: 1.06-5.93, p = 0.04) were the promoting factors for MII oocyte rate. Conclusion: Flaxseed oil improved ovarian response and the quality of oocytes and embryos, thereby increasing the fertilization rate and high-quality embryo rate in DOR patients. The use of flaxseed oil was positively correlated with MII oocyte rate in women with DOR. Clinical trial number: https://www.chictr.org.cn/, identifier ChiCTR2300073785.

Pirfenidone improves early cardiac function following myocardial infarction by enhancing the elastin/collagen ratio.

BACKGROUND: Acute myocardial infarction (AMI) is a leading cause of mortality worldwide, with reduced elastin/collagen ratios exacerbating cardiac dysfunction due to collagen-rich scar tissue replacing necrotic myocardial cells. This study aims to evaluate pirfenidone's therapeutic effect on early cardiac function post-AMI and elucidate its impact on the elastin/collagen ratio. METHODS: Sprague-Dawley rats were divided into four groups: Sham, AMI, AMI treated with PBS (AMI-PBS), and AMI treated with pirfenidone (AMI-PFD) (n=12 each). AMI was induced via coronary artery ligation. The AMI-PFD and AMI-PBS groups received pirfenidone and PBS for 14 days, respectively. Cardiac function, fibrosis, serum cytokines, collagen and elastin content, and their ratios were assessed. Cardiac fibroblasts (CFs) from neonatal rats were categorized into control, hypoxia-induced (LO), LO+PBS, and LO+PFD groups. ELISA measured inflammatory factors, and RT-PCR analyzed collagen and elastin gene expression. RESULTS: The AMI-PFD group showed improved cardiac function and reduced serum interleukin-1ß (IL-1ß), IL-6, and transforming growth factor-ß (TGF-ß). Type I and III collagen decreased by 22.6 % (P=0.0441) and 34.4 % (P=0.0427), respectively, while elastin content increased by 79.4 % (P=0.0126). E/COLI and E/COLIII ratios rose by 81.1 % (P=0.0026) and 88.1 % (P=0.0006). CFs in the LO+PFD group exhibited decreased IL-1ß, IL-6, TGF-ß, type I and III collagen, with increased elastin mRNA, enhancing the elastin/collagen ratio. CONCLUSION: Pirfenidone enhances cardiac function by augmenting the early elastin/collagen ratio post-AMI.

Weak magnetic field promotes denitrification by stimulating ferromagnetic ion-containing metalloprotein expression.

Weak magnetic field (WMF) has been recognized to promote biological denitrification processes; however, the underlying mechanisms remain largely unexplored, hindering the optimization of its effectiveness. Here, we systematically investigated the effects of WMF on denitrification performance, enzyme activity, microbial community, and metaproteome in packed bed bioreactors treating high nitrate wastewater under different WMF intensities and C:N ratios. Results showed that WMFs significantly promoted denitrification by consistently stimulating the activities of denitrifying reductases and NAD+/NADH biosynthesis across decreasing C:N ratios. Reductases and electron transfer enzymes involved in denitrification were overproduced due to the significantly enriched overexpression of ferromagnetic ion-containing (FIC) metalloproteins. We also observed WMFs' intensity-dependent selective pressure on microbial community structures despite the effects being limited compared to those caused by changing C:N ratios. By coupling genome-centric metaproteomics and structure prediction, we found the dominant denitrifier, Halomonas, was outcompeted by Pseudomonas and Azoarcus under WMFs, likely due to its structural deficiencies in iron uptake, suggesting that advantageous ferromagnetic ion acquisition capacity was necessary to satisfy the substrate demand for FIC metalloprotein overproduction. This study advances our understanding of the biomagnetic effects in the context of complex communities and highlights WMF's potential for manipulating FIC protein-associated metabolism and fine-tuning community structure.

Iron metabolism and arthritis: Exploring connections and therapeutic avenues.

ABSTRACT: Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

Intrapericardial Administration of Human Pericardial Fluid Cells Improves Cardiac Functions in Rats with Heart Failure.

Heart failure is still the main cause of mortality worldwide. This study investigated the characteristics of human pericardial fluid-derived cells (hPFCs) and their effects in treating doxorubicin (DOX)-induced heart failure (HF) rats through intrapericardial injection. hPFCs were isolated from patients who underwent heart transplantation (N=5). These cells that primarily expressed SCA-1, NANOG, mesenchymal markers CD90, CD105 and CD73, were able to form adipocytes, osteoblasts, and cardiomyocytes in vitro. Passage 3 hPFCs (2.5 ×105 cells/heart) were injected into the pericardial cavity of the doxorubicin (DOX)-injured rat hearts, significantly improving cardiac functions after 4 weeks. The tracked and engrafted RFP-tagged hPFCs co-expressed cardiac troponin T and connexin 43 after 4 weeks in the host myocardium. This observation was also coupled with a significant reduction in cardiac fibrosis following hPFCs treatment (P<0.0001 versus untreated). The elevated inflammatory cytokine IL-6, IL-10, and TNF-α in the DOX-treated hearts were found to have significantly reduced (P<0.001 versus untreated), while the regional pro-angiogenic vascular endothelial growth factor A (VEGFA) level was increased in the hPFCs-treated group after 4 weeks (P<0.05 versus untreated). hPFCs possess stem cell characteristics and can improve cardiac functions of DOX-induced heart failure rats after 4 weeks through pericardial administration. The improvements were attributed to a significant reduction in cardiac fibrosis, inflammation, and elevated regional pro-angiogenesis factor VEGFA, with evidence of cellular engraftment and differentiation in the host myocardium.

Single-cell RNA sequencing reveals the CRTAC1+ population actively contributes to the pathogenesis of spinal ligament degeneration by SPP1+ macrophage.

Degenerative spinal stenosis is a chronic disease that affects the spinal ligaments and associated bones, resulting in back pain and disorders of the limbs among the elderly population. There are few preventive strategies for such ligament degeneration. We here aimed to establish a comprehensive transcriptomic atlas of ligament tissues to identify high-priority targets for pharmaceutical treatment of ligament degeneration. Here, single-cell RNA sequencing was performed on six degenerative ligaments and three traumatic ligaments to understand tissue heterogeneity. After stringent quality control, high-quality data were obtained from 32,014 cells. Distinct cell clusters comprising stromal and immune cells were identified in ligament tissues. Among them, we noted that collagen degradation associated with CTHRC1+ fibroblast-like cells and calcification linked to CRTAC1+ chondrocyte-like cells were key features of ligament degeneration. SCENIC analysis and further experiments identified ATF3 as a key transcription factor regulating the pathogenesis of CRTAC1+ chondrocyte-like cells. Typically, immune cells infiltrate localized organs, causing tissue damage. In our study, myeloid cells were found to be inflammatory-activated, and SPP1+ macrophages were notably enriched in degenerative ligaments. Further exploration via CellChat analysis demonstrated a robust interaction between SPP1+ macrophages and CRTAC1+ chondrocyte-like cells. Activated by SPP1, ATF3 propels the CRTAC1/MGP/CLU axis, fostering ligament calcification. Our unique resource provides novel insights into possible mechanisms underlying ligament degeneration, the target cell types, and molecules that are expected to mitigate degenerative spinal ligament. We also highlight the role of immune regulation in ligament degeneration and calcification, enhancing our understanding of this disease.