Exosomes from adipose-derived stem cells overexpressing microRNA-671-3p promote fat graft angiogenesis and adipogenic differentiation.

Exosomes from adipose-derived stem cells (ADSCs) have been demonstrated to benefit angiogenesis, wound healing, and fat grafting. Small noncoding RNAs such as microRNA (miRNA) and circular RNA play critical roles in mediating the function of ADSCs-derived exosomes. However, the underlying mechanisms have not been fully elucidated. In this study, we investigated the function and mechanism of human ADSCs-derived exosomes (hADSCs-Exo) in promoting fat graft angiogenesis and adipogenic differentiation. hADSCs-Exo were isolated and identified, and treatment with hADSCs-Exo enhanced fat graft angiogenesis and adipogenic differentiation in a mouse fat graft implantation model. We found that hADSCs-Exo overexpressed miR-671-3p and promoted human umbilical vein endothelial cell (HUVEC) proliferation, migration, and invasion. Bioinformatics analysis and luciferase reporter assay validated that TMEM127 is a direct target of miR-671-3p. Rescue experiments demonstrated that TMEM127 overexpression partially antagonized the function of hADSCs-Exo in vitro, such as suppressing HUVEC cell proliferation, migration, and invasion. Moreover, TMEM127 overexpression abrogated the function of hADSCs-Exo on fat graft angiogenesis and adipogenic differentiation. Taken together, our findings demonstrate that miR-671-3p-overexpressing exosomes from ADSC promote fat graft angiogenesis and adipogenic differentiation, which highlights the potential of targeting the ADSC-Exosomes-miR-671-3p/TMEM127 axis to improve outcome of fat graft and tissue engineering regenerative medicine.

Phillyrin prevents sepsis-induced acute lung injury through inhibiting the NLRP3/caspase-1/GSDMD-dependent pyroptosis signaling pathway.

Acute lung injury (ALI) is a severe pulmonary disorder of sepsis with high clinical incidence and mortality. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)-cysteinyl aspartate specific proteinase 1-gasdermin D (GSDMD)-dependent pyroptosis of alveolar epithelial cells (AECs) has emerged as a crucial contributor to ALI during sepsis. Phillyrin (PHI), a natural lignan isolated from the traditional Chinese herbal medicine Forsythia suspensa, has been shown to have anti-inflammatory, antioxidant and antiviral properties. However, little is known about the protective role and potential mechanism of PHI in sepsis-induced ALI, and it is uncertain whether the protective effect of PHI in sepsis-induced ALI is connected to pyroptosis. This study aims to examine the preventive effects of PHI on sepsis-induced ALI via the inhibition of NLRP3/caspase-1/GSDMD-mediated pyroptosis in AECs. Our findings demonstrate that preadministration of PHI successfully reduces sepsis-induced pulmonary edema, systemic/pulmonary inflammation, and pulmonary histological damage in lung tissues, bronchoalveolar lavage fluid, and the serum of septic mice. Intriguingly, PHI preadministration suppresses sepsis-induced protein expressions of pyroptosis-specific markers, especially their active forms. In vitro assays show that PHI pretreatment also protects type II AECs (MLE-12) from lipopolysaccharide-induced pyroptosis by preventing the activation of the pyroptosis signaling pathway. The results from molecular docking and surface plasmon resonance reveal that PHI has a significant affinity for direct binding to the GSDMD protein, suggesting that GSDMD is a potential pharmacological target for PHI. In conclusion, PHI can prevent sepsis-triggered ALI by effectively suppressing the activation of the canonical pyroptosis signaling pathway and pyroptosis of AECs.

Human midbrain organoids: a powerful tool for advanced Parkinson's disease modeling and therapy exploration.

Parkinson's disease (PD) is a neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra. Despite progress, the pathogenesis remains unclear. Human midbrain organoids (hMLOs) have emerged as a promising model for studying PD, drug screening, and potential treatments. This review discusses the development of hMLOs, their application in PD research, and current challenges in organoid construction, highlighting possible optimization strategies.

Single-cell sequencing insights into the transcriptional landscape of Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, with an unknown etiology and no specific treatment. Emerging single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have become instrumental in unravelling cellular heterogeneity and characterizing molecular signatures at single-cell resolution. Single-cell T cell receptor sequencing (scTCR-seq) and single-cell B cell receptor sequencing (scBCR-seq) technologies provide unprecedented opportunities to explore the immune repertoire diversity. These state-of-the-art technologies have been increasingly applied in PD research in the last five years, offering novel insights into the cellular susceptibilities and complex molecular mechanisms underlying PD pathogenesis. Herein we review recent advances in the applications of sc/snRNA-seq, scTCR-seq and scBCR-seq technologies in various PD models. Moreover, we focus on degenerative neurons, activated neuroglial cells, as well as pro-inflammatory immune cells, exploring their unique transcriptional landscapes in PD, as revealed by single-cell sequencing technologies. Finally, we highlight important challenges and the future directions of single-cell experiments in PD research.

Application of Eight Machine Learning Algorithms in the Establishment of Infertility and Pregnancy Diagnostic Models: A Comprehensive Analysis of Amino Acid and Carnitine Metabolism.

To explore the effects of altered amino acids (AAs) and the carnitine metabolism in non-pregnant women with infertility (NPWI), pregnant women without infertility (PWI) and infertility-treated pregnant women (ITPW) compared with non-pregnant women (NPW, control), and develop more efficient models for the diagnosis of infertility and pregnancy, 496 samples were evaluated for levels of 21 AAs and 55 carnitines using targeted high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Three methods were used to screen the biomarkers for modeling, with eight algorithms used to build and validate the model. The ROC, sensitivity, specificity, and accuracy of the infertility diagnosis training model were higher than 0.956, 82.89, 66.64, and 82.57%, respectively, whereas those of the validated model were higher than 0.896, 77.67, 69.72, and 83.38%, respectively. The ROC, sensitivity, specificity, and accuracy of the pregnancy diagnosis training model were >0.994, 96.23, 97.79, and 97.69%, respectively, whereas those of the validated model were >0.572, 96.39, 93.03, and 94.71%, respectively. Our findings indicate that pregnancy may alter the AA and carnitine metabolism in women with infertility to match the internal environment of PWI. The developed model demonstrated good performance and high sensitivity for facilitating infertility and pregnancy diagnosis.

Identifying potential causal effects of Parkinson's disease: A polygenic risk score-based phenome-wide association and mendelian randomization study in UK Biobank.

There is considerable uncertainty regarding the associations between various risk factors and Parkinson's Disease (PD). This study systematically screened and validated a wide range of potential PD risk factors from 502,364 participants in the UK Biobank. Baseline data for 1851 factors across 11 categories were analyzed through a phenome-wide association study (PheWAS). Polygenic risk scores (PRS) for PD were used to diagnose Parkinson's Disease and identify factors associated with PD diagnosis through PheWAS. Two-sample Mendelian randomization (MR) analysis was employed to assess causal relationships. PheWAS results revealed 267 risk factors significantly associated with PD-PRS among the 1851 factors, and of these, 27 factors showed causal evidence from MR analysis. Compelling evidence suggests that fluid intelligence score, age at first sexual intercourse, cereal intake, dried fruit intake, and average total household income before tax have emerged as newly identified risk factors for PD. Conversely, maternal smoking around birth, playing computer games, salt added to food, and time spent watching television have been identified as novel protective factors against PD. The integration of phenotypic and genomic data may help to identify risk factors and prevention targets for PD.

Microvascular and cellular dysfunctions in Alzheimer's disease: an integrative analysis perspective.

Alzheimer's disease (AD) is the most common cause of dementia, characterized by memory loss, cognitive decline, personality changes, and various neurological symptoms. The role of blood-brain barrier (BBB) injury, extracellular matrix (ECM) abnormalities, and oligodendrocytes (ODCs) dysfunction in AD has gained increasing attention, yet the detailed pathogenesis remains elusive. This study integrates single-cell sequencing of AD patients' cerebrovascular system with a genome-wide association analysis. It aims to elucidate the associations and potential mechanisms behind pericytes injury, ECM disorder, and ODCs dysfunction in AD pathogenesis. Finally, we identified that abnormalities in the pericyte PI3K-AKT-FOXO signaling pathway may be involved in the pathogenic process of AD. This comprehensive approach sheds new light on the complex etiology of AD and opens avenues for advanced research into its pathogenesis and therapeutic strategies.

Decomposition Model of Bastnaesite and Its Fluorine Oxygen Coupling Escape Mechanism.

Nearly 90% of rare earths worldwide currently originate from bastnaesite (REFCO3). Oxidative roasting, an effective method for the treatment of bastnaesite, has been extensively employed in industrial production practice. However, the roasting decomposition mechanism of bastnaesite at the molecular level remains controversial. In this study, two roasting atmospheres (i.e., Ar and O2) were adopted for the treatment of the mixed rare earth concentrate in Bayan Obo. Ar-Roasting ore was skillfully treated as an intermediate and then underwent oxidation roasting. The results achieved using research methods (e.g., XRD, FT-IR, TEM, and XPS) first revealed that the oxidation roasting of bastnaesite was performed in several stages. The first stage was the thermal decomposition of bastnaesite and the oxidation of cerium (REFCO3 → REOF + CO2). The second stage was the escape pathway of fluorine (REOF + O2 → RE x O y + O x F and O x F → O2 + F2), describing the migration rules of F and O elements and the oxidation behavior of Ce. The results of this study can provide more theoretical support and guidance for the clean extraction of bastnaesite and mixed rare earth in Bayan Obo.

Anemia, blood cell indices, genetic correlations, and brain structures: A comprehensive analysis of roles in Parkinson's disease risk.

INTRODUCTION: Anemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study. METHODS: We used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume. RESULTS: During a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81-2.18, P < 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk. CONCLUSION: In summary, we consider there to be a substantial correlation between anemia and increased PD risk.

Identification of immune-related biomarkers for intracerebral hemorrhage diagnosis based on RNA sequencing and machine learning.

Background: Intracerebral hemorrhage (ICH) is a severe stroke subtype with high morbidity, disability, and mortality rates. Currently, no biomarkers for ICH are available for use in clinical practice. We aimed to explore the roles of RNAs in ICH pathogenesis and identify potential diagnostic biomarkers. Methods: We collected 233 individual blood samples from two independent cohorts, including 64 patients with ICH, 59 patients with ischemic stroke (IS), 60 patients with hypertension (HTN) and 50 healthy controls (CTRL) for RNA sequencing. Differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), and weighted correlation network analysis (WGCNA) were performed to identify ICH-specific modules. The immune cell composition was evaluated with ImmuneCellAI. Multiple machine learning algorithms to select potential biomarkers for ICH diagnosis, and further validated by quantitative real-time polymerase chain reaction (RT-PCR). Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate the diagnostic value of the signature for ICH. Finally, we generated M1 and M2 macrophages to investigate the expression of candidate genes. Results: In both cohorts, 519 mRNAs and 131 lncRNAs were consistently significantly differentially expressed between ICH patients and HTN controls. Gene function analysis suggested that immune system processes may be involved in ICH pathology. ImmuneCellAI analysis revealed that the abundances of 11 immune cell types were altered after ICH in both cohorts. WGCNA and GSEA identified 18 immune-related DEGs. Multiple algorithms identified an RNA panel (CKAP4, BCL6, TLR8) with high diagnostic value for discriminating ICH patients from HTN controls, CTRLs and IS patients (AUCs: 0.93, 0.95 and 0.82; sensitivities: 81.3%, 84.4% and 75%; specificities: 100%, 96% and 79.7%, respectively). Additionally, CKAP4 and TLR8 mRNA and protein levels decreased in RAW264.7 M1 macrophages and increased in RAW264.7 M2 macrophages, while BCL6 expression increased in M1 macrophages but not in M2 macrophages, which may provide potential therapeutic targets for ICH. Conclusions: This study demonstrated that the expression levels of lncRNAs and mRNAs are associated with ICH, and an RNA panel (CKAP4, BCL6, TLR8) was developed as a potential diagnostic tool for distinguishing ICH from IS and controls, which could provide useful insight into ICH diagnosis and pathogenesis.

A case report of fifteen-and-a-half syndrome.

BACKGROUND: Fifteen-and-a-Half Syndrome is an uncommon clinical presentation characterized by the coexistence of one-and-a-half syndrome and bilateral facial palsy. In this study, we provide a comprehensive description of symptom evolution and imaging changes in a patient with Fifteen-and-a-Half Syndrome. CASE PRESENTATION: A 54-year-old male presented with sudden onset of one-and-a-half syndrome, which gradually progressed to fifteen-and-a-half syndrome. The final diagnosis was confirmed to be pontine infarction which occurred at the midline of the pontine tegmentum. CONCLUSION: This case highlights the diverse and progressive early clinical manifestations associated with Fifteen-and-a-half Syndrome. Currently, all reported cases of this syndrome are linked to brainstem infarction; however, early differential diagnosis is crucial to ensure prompt initiation of appropriate treatment for affected patients.

Left atrial mechanical dispersion and left atrial stiffness predicts recurrence of atrial fibrillation: In patients with moderate-severe rheumatic mitral stenosis.

AIMS: The aim of this study was to evaluate the relationship between preoperative left atrial function and recurrence of atrial fibrillation (AF) after mitral valve surgery and Cox Maze procedure in patients with moderate-to-severe rheumatic mitral stenosis (MS) combined with AF, in order to facilitate clinical risk stratification and to guide treatment strategies. METHODS AND RESULTS: Patients with moderate-to-severe rheumatic MS attending Beijing Anzhen Hospital of Capital Medical University from April 2022 to September 2023 were prospectively collected, and all of them underwent transthoracic two-dimensional speckle-tracking echocardiography to assess left atrial structure and function before undergoing mitral valve surgery and Cox Maze procedure and postoperative follow-up. 121 patients were enrolled, of whom 77.69 % (94/121) were female, with a median follow-up time of 9.56 ± 1.83 months, and 48 patients (39.7 %, 48/121) had postoperative recurrence of AF. Preoperative left atrial stiffness index (LASI) [3.76(3.10-5.44) vs. 2.41(1.75-3.33), P < 0.001] and left atrial mechanical dispersion (SD-TPS) (15.84 ± 5.92vs. 11.58 ± 5.96, P = 0.001) were significantly higher in the postoperative AF recurrence group than in the without recurrence group; Multivariable cox regression analysis showed that LASI>3.15 and SD -TPS > 13.2 were associated with independent risk factors for AF recurrence (hazard ratio = 2.957, 95 %CI,1.366-6.399, P = 0.006 and hazard ratio = 2.892, 95 %CI,1.381-6.057, P = 0.005). CONCLUSION: LASI and SD-TPS were effective predictors of postoperative recurrence of AF in patients with moderate-to-severe rheumatic MS, and LASI >3.15 and SD-TPS% >13.2 were independent influences on the recurrence of AF after Cox Maze in this group of patients.

A novel role of the cotton calcium sensor CBL3 was involved in Verticillium wilt resistance in cotton.

BACKGROUND: Verticillium wilt, causes mainly by the soilborne pathogen Verticillium dahliae, is a devastated vascular disease resulting in huge financial losses in cotton, so research on improving V. dahliae stress tolerance in cotton is the utmost importance. Calcium as the second messenger acts as a crucial role in plant innate immunity. Cytosolic Ca2+during the pathogen infection is a significant increase in plant immune responses. Calcineurin B-like (CBL) proteins are widely known calcium sensors that regulate abiotic stress responses. However, the role of cotton CBLs in response to V. dahliae stress remains unclear. OBJECTIVE: To discover and utilize the gene to Verticillium wilt resistance and defense response mechanism of cotton. METHODS: Through screening the gene to Verticillium wilt resistance in cotton, four GhCBL3 copies were obtained from the current common cotton genome sequences. The protein domain and phylogenetic analyses of GhCBL3 were performed using NCBI Blast, DNAMAN, and MotifScan programs. Real-time RT-PCR was used to detect the expression of GhCBL3 gene in cotton seedlings under various stress treatments. The expression construct including GhCBL3 cDNA was transduced into Agrobacterium tumefaciens (GV3101) by heat shock method and transformed into cotton plants by Virus-Induced Gene Silencing (VIGS) method. The results of silencing of GhCBl3 on ROS accumulation and plant disease resistance in cotton plants were assessed. RESULTS: A member of calcineurin B-like proteins (defined as GhCBL3) in cotton was obtained. The expression of GhCBL3 was significantly induced and raised by various stressors, including dahliae, jasmonic acid (JA) and H2O2 stresses. Knockdown GhCBL3 in cotton by Virus-Induced Gene Silencing analysis enhanced Verticillium wilt tolerance and changed the occurrence of reactive oxygen species. Some disease-resistant genes were increased in GhCBL3-silencing cotton lines. CONCLUSION: GhCBL3 may function on regulating the Verticillium dahliae stress response of plants.

The potential protective role of peripheral immunophenotypes in Alzheimer's disease: a Mendelian randomization study.

Introduction: Alzheimer's disease (AD) is the most widespread neurodegenerative disease in the world. Previous studies have shown that peripheral immune dysregulation plays a paramount role in AD, but whether there is a protective causal relationship between peripheral immunophenotypes and AD risk remains ambiguous. Methods: Two-sample Mendelian randomization (MR) was performed using large genome-wide association study (GWAS) genetic data to assess causal effects between peripheral immunophenotypes and AD risk. Utilizing the genetic associations of 731 immune cell traits as exposures. We adopted the inverse variance weighted method as the primary approach. The Weighted median and MR-Egger regression methods were employed as supplements. Various sensitivity analyses were performed to assess the robustness of the outcomes. Results: Based on the IVW method, we identified 14 immune cell traits that significantly reduced the risk of AD, of which six demonstrated statistical significance in both IVW and Weighted median methods. Among the seven immune traits, four were related to regulatory T (Treg) cells : (1) CD25++ CD45RA- CD4 not regulatory T cell % T cell (odds ratio (OR) [95% confidence interval (CI)] = 0.96 [0.95, 0.98], adjusted P = 1.17E-02), (2) CD25++ CD45RA- CD4 not regulatory T cell % CD4+ T cell (OR [95% CI] = 0.97 [0.96, 0.99], adjusted P = 3.77E-02), (3) Secreting CD4 regulatory T cell % CD4 regulatory T cell (OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E-03), (4) Activated & secreting CD4 regulatory T cell % CD4 regulatory T cell(OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E-03). In addition, HLA DR++ monocyte % monocyte (OR [95% CI] = 0.93 [0.89, 0.98], adjusted P = 4.87E-02) was associated with monocytes, and HLA DR on myeloid Dendritic Cell (OR [95% CI] = 0.93 [0.89, 0.97], adjusted P = 1.17E-02) was related to dendritic cells (DCs). Conclusion: These findings enhance the comprehension of the protective role of peripheral immunity in AD and provide further support for Treg and monocyte as potential targets for immunotherapy in AD.

Air pollution, greenspace exposure and risk of Parkinson's disease: a prospective study of 441,462 participants.

BACKGROUND: The current understandings of the relationship between air pollution (AP), greenspace exposure and Parkinson's Disease (PD) remain inconclusive. METHODS: We engaged 441,462 participants from the UK Biobank who were not diagnosed with PD. Utilizing Cox proportional hazard regression model, relationships between AP [nitrogen dioxide (NO2), and nitrogen oxides (NOX), particulate matter < 2.5 µm in aerodynamic diameter(PM2.5), coarse particulate matter between 2.5 µm and 10 µm in aerodynamic diameter(PM2.5-10), particulate matter < 10 µm in aerodynamic diameter(PM10)], greenspace exposure, and PD risk were determined independently. Our analyses comprised three models, adjusted for covariates, and affirmed through six sensitivity analyses to bolster the robustness of our findings. Moreover, mediation analysis was deployed to discern the mediating effect of AP between greenspaces and PD. RESULTS: During a median follow-up of 12.23 years (5,574,293 person-years), there were 3,293 PD events. Each interquartile (IQR) increment in NO2 and PM10 concentrations were associated with 10% and 8% increase in PD onset risk, while the increases in NOX, PM2.5 and PM2.5-10 were not associated with PD risk. Additionally, greenspace may safeguard by reducing NO2 and PM10 levels, with the effect mediated by NO2 and PM10 in greenspace-PD relationship. CONCLUSION: Our findings indicate that an IQR increase in ambient NO2 and PM10 concentrations was associated with risk of PD development, while other pollutants (NOX, PM2.5 and PM2.5-10) were not associated with PD risk. Firstly, we find that augmented exposure to greenspace was associated with the lower PD risk by reducing NO2 and PM10 levels.

Waistline to thigh circumference ratio as a predictor of MAFLD: a health care worker study with 2-year follow-up.

BACKGROUND: This study aimed to determine whether the waist-to-thigh ratio (WTTR) is associated with the incidence of metabolic-associated fatty liver disease (MAFLD) in health care workers. METHODS: There were 4517 health care workers with baseline data and results from 2 follow-up examinations. We divided the subjects into 3 groups according to baseline WTTR and used the Cox hazard regression model to estimate MAFLD risk. RESULTS: The WTTRs were categorized by tertiles at baseline using the values 1.58 and 1.66. Patients with higher WTTR tended to have significantly greater values for the following factors, body mass index (BMI), fasting blood glucose (FPG), systolic blood pressure, diastolic blood pressure, total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C) and neck circumference. The incidence of MAFLD significantly increased with increasing WTTR tertiles (5.74%, 12.75% and 22.25% for the first, second and third tertiles, respectively, P < 0.05 for trend). Kaplan-Meier(K-M) survival analysis revealed a significant tendency towards increased MAFLD risk with increasing WTTR tertile. In the fully adjusted model, the hazard ratios (95% CIs) for MAFLD in the second, third WTTR tertiles compared with the first quartile were 2.17(1.58,2.98), 3.63(2.70,4.89), respectively, third neck circumference tertiles compared with the first quartile were 2.84(1.89,4.25), 8.95(6.00,13.35), respectively. Compared with those of individuals with a BMI > 23 kg/m2, the associations between WTTR and MAFLD incidence were more pronounced in subjects with a BMI < 23 kg/m2. Similarly, the difference in neck circumference was more pronounced in these patients with a BMI < 23 kg/m2. CONCLUSIONS: Our results revealed that the WTTR is an independent risk factor for MAFLD, and there was a dose‒response relationship between the WTTR and MAFLD risk. The neck circumference was significantly different in subjects with a BMI < 23 kg/m2. This approach provides a new way to predict the incidence rate of MAFLD.

Generation of a TSC2 knockout embryonic stem cell line by CRISPR/Cas9 editing.

Tuberous Sclerosis Complex (TSC) is a severe developmental disorder with various clinical effects, primarily caused by TSC2 gene mutations, often involving loss of function(Henske,et al., 2016).To explore role of TSC2 in human heart development, we successfully developed a TSC2 knockout (TSC2-/-) human embryonic stem cells (hESCs) line using CRISPR/Cas9 gene editing. This TSC2-/- hESC line maintained a normal karyotype, expressed pluripotency markers strongly, and could differentiate into all three germ layers in vivo. This cell line will be a valuable tool for future research on the role of TSC2 in heart development.

Maternal exposure to ambient ozone and fetal conotruncal heart defects in China: A multicenter cohort study.

BACKGROUND: The relationships between maternal genetic and environmental exposure and conotruncal heart defects (CTDs) have been extensively investigated. Nevertheless, there is limited knowledge regarding the impact of ozone (O3) on the risk of CTDs. OBJECTIVE: To explore the correlation between maternal exposure to O3 and CTDs in China. METHODS: Pregnant women who underwent fetal echocardiography at Beijing Anzhen Hospital between January 2013 and December 2021 were enrolled. Their sociodemographic characteristics and lifestyle information, along with fetal data, were systematically collected. Fetal echocardiography was used to detect CTDs. Maternal exposure to ambient O3 during the embryonic period, the first trimester, the three months preceding the last menstrual period, and the perinatal period was estimated using residential addresses or hospital addresses associated with prenatal visits. The concentration of O3 was divided by quartiles, with the first quartile serving as a reference. Adjusted logistic regression models were employed to examine the associations between every 10 µg/m3 increase or quartile increase in ambient O3 exposure and CTDs. RESULTS: Among 24,278 subjects, 1069 exhibited fetuses with CTDs. Maternal exposure to ambient O3 during three pregnancy periods was associated with increased CTD risk. The adjusted odds ratio (OR) and 95% confidence interval (CI) were 1.271 (1.189-1.360) per 10 µg/m3 increase in O3 during the perinatal period. For each quartile of O3, the risk increased with increasing exposure concentration, particularly during the perinatal period (OR = 2.206 for quartile 2, 2.367 for quartile 3, and 3.378 for quartile 4, all P<0.05). CONCLUSIONS: Elevated maternal exposure to O3 during pregnancy, particularly in the perinatal period, is linked to an increased risk of fetal CTDs. Further longitudinal analyses are needed to validate these results.