DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

Parkinson's disease (PD), a major neurodegenerative disease faced by an aging society worldwide, has not yet been fully elucidated in terms of its pathogenesis. Currently, clinical treatment mainly relies on symptom management and can only be relieved by medication. In recent years, many studies have shown that polysaccharides have potential in treatment of neurodegenerative diseases. Polysaccharides play a role in PD in ways such as anti-oxidative stress response, improvement of mitochondrial dysfunction, inhibition of neuroinflammation, anti-neurotoxicity, and activation of autophagy. This study discusses the mechanism of polysaccharides in PD, aiming to provide new ideas for PD prevention and treatment and new drug development in the future.

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective: To comprehensively evaluate the clinical efficacy of a single dose of tranexamic acid (TXA) in reducing perioperative blood loss in patients undergoing craniomaxillofacial plastic and cosmetic surgery through meta-regression analysis. Methods: Embase, PubMed, Wanfang Data, VIP database, China National Knowledge Infrastructure (CNKI), the Chinese Clinical Trial Registry (ChiCTR) and Cochrane Central Register of Controlled Trials (CENTRAL) were electronically retrieved to collect clinical studies evaluating efficacy of perioperative TXA administration in patients undergoing craniomaxillofacial plastic and cosmetic surgery, from inception to August 2024. Quality assessment of randomized controlled trials (RCTs) was performed using Cochrane Collaboration's Risk of Bias Tool. Based on the results of methodological heterogeneity, corresponding meta-analyses were conducted using either random-effects or fixed-effects models in R programming software. Results: Thirty-one articles were included, involving 2 072 patients who underwent craniomaxillofacial plastic and cosmetic surgeries. Among these patients, 1 051 were in the TXA treatment group, and 1 021 were in the control group. The paired meta-analysis showed that compared with the control group, the use of TXA significantly reduced bleeding volume in perioperative patients [standardized mean difference (SMD)=-1.13; 95%CI (-1.47, -0.80), P<0.001]. Subgroup analysis revealed that TXA significantly reduced intraoperative bleeding volume in patients across different surgeries, with the order of efficacy as follows: orthognathic surgery [SMD=-1.44; 95%CI (-2.07, -0.80), P<0.001], cleft palate repair [SMD=-1.32; 95%CI (-2.14, -0.50), P<0.001], rhinoplasty [SMD=-0.97; 95%CI (-1.63, -0.30), P<0.001], and craniosynostosis [SMD=-0.96; 95%CI (-1.40, -0.53), P=0.040]. The result of the meta regression showed there was no significant difference in the hemostatic effect of TXA on patients with increasing doses (5, 10, 15, 20, 25 mg/kg) (P=0.650). Sensitivity analysis verified that the pooled values were stable and reliable. The Egger's test indicated a certain degree of publication bias (Z=-3.40, P<0.001). Conclusion: Existing evidence suggests that TXA effectively reduces perioperative blood loss in patients undergoing craniofacial plastic surgery, regardless of its dosage administered.

Objective:To comprehensively evaluate the clinical effectiveness with respect to a single dose of tranexamic acid (TXA) given preoperatively for blood loss control in perioperative patients accepted craniomaxillofacial plastic and cosmetic surgery.Methods:Embase, PubMed, WanFang Data, VIP, China National Knowledge Infrastructure (CNKI), the Chinese Clinical Trial Registry (ChiCTR) and Cochrane Central Register of Controlled Trials (CENTRAL) were electronically retrieved to collect randomized controlled trials (RCTs) related to appraise the efficacy in perioperative craniomaxillofacial plastic and cosmetic surgery patients used TXA from inception to August 2024. Based on the result of methodological heterogeneity, corresponding paired meta-analyses were carried out with a random-effects or fixed-effects model applying R 4.0.4 software. Subgroup analysis was performed based on type of surgery, patient age, regional distribution of patients, and sample size included in the studies. A meta-regression analysis was performed on studies that reported the effect of different doses of TXA on reducing perioperative bleeding. Sensitivity analysis was performed to verify the stability of the meta result. Egger’s test was used to analyze potential publication bias.Results:A total of 31 RCTs were included, involving 2 072 patients, with 1 051 in the TXA group and 1 021 in the placebo group. The paired meta-analysis random-effects model ( I2=90%) showed that compared with the control group, the use of TXA significantly reduced the amount of bleeding in perioperative patients[standardized mean difference ( SMD)=-1.13, 95% CI -1.47 to -0.80, P < 0.01]. Subgroup analysis revealed that TXA had a significant effect on reducing intraoperative bleeding in patients with different surgeries, ages, regions, and sample sizes. The most effective subgroups were cases in orthognathic surgery ( SMD=-1.44, 95% CI -2.07 to -0.80, P< 0.01), less than 30 year-old( SMD=-1.32, 95% CI -1.68 to -0.96, P< 0.01], Asian patients( SMD=-1.29, 95% CI -1.72 to -0.86, P< 0.01), less than 30 individuals ( SMD=-1.16, 95% CI -1.50 to -0.82, P< 0.01). The result of the meta regression showed there was no significant difference in the hemostatic effect of TXA on patients with increasing doses (5, 10, 15, 20, 25 mg/kg) ( P>0.05). Sensitivity analysis verified that the pooled values were stable and reliable. The Egger’s test indicated a certain degree of publication bias ( P < 0.01). Conclusion:Taken as a whole, existing evidence suggests that TXA can effectively reduce perioperative bleeding in patients undergoing craniofacial plastic surgery, regardless of its dosage administered. However, further clinical researches are still needed to provide more baselined data, transfusion-related indicators, and information on adverse events such as vascular embolism, in order to comprehensively evaluate and analyze the efficacy and safety of a single dose of TXA for perioperative blood loss control in patients treated with craniomaxillofacial plastic and cosmetic surgery.

Objective:Hearing loss can seriously affect mental health status, and this study aims to investigate the influence of hearing health status on depressive symptoms among middle-aged and older individuals in the community.Methods:From June to December 2023, a stratified random sampling method was employed to select 1 238 community-dwelling middle-aged and elderly people aged 45 years and above from four cities (Hangzhou, Shanghai, Baoding, and Zhengzhou) as research subjects. A questionnaire survey was conducted to collect the subjects′ basic information, hearing health status [assessed by the Hearing Handicap Inventory for Adults-Screening Version (HHIA-S)], and depressive symptoms [assessed by the Geriatric Depression Scale-15 (GDS-15)]. T-tests, rank-sum tests and chi-square tests were used for univariate analysis, while, multiple linear regression and binary Logistic regression were applied to analyze the relationship between hearing health status and depressive symptoms.Results:A total of 1 183 community-dwelling middle-aged and elderly people aged 45 years and above were included in the final analysis (464 males and 719 females, aged from 45 to 96 years). The detection rate of hearing loss was 35.3%(418/1 183), while, the detection rate of depressive symptoms was 9.89%(117/1 183). Age, level of interaction with children, self-rated health, perceived loneliness, and hearing health significantly influenced depressive symptoms among older adults residing in the community ( P<0.05). Individuals with moderate to severe hearing loss ( β=2.04, 95% CI: 1.47, 2.62) exhibited higher GDS-15 scores compared to those without hearing impairment. Furthermore, after correcting for sex, age, marital status, monthly per capita family income, education, residence, smoking status, alcohol use, use of psychotropic medication (anxiolytic or depressant), number of illness, self-health assessment, and autonomy, middle-aged and older adults with mild to moderate hearing loss ( OR=2.89, 95% CI: 1.76, 4.88) and severe hearing loss ( OR=5.79, 95% CI: 3.05, 11.01) demonstrated an increased likelihood of experiencing depression. Conclusions:The degree of hearing loss in community-dwelling middle-aged and elderly individuals is closely associated with the risk of depressive symptoms. Therefore, it is imperative to enhance hearing health screening and to provide mental health support to individuals with hearing loss, in order to mitigate the onset and progression of depressive symptoms.

Objective:To investigate the influence of prealbumin on cerebral infarction severity, hemorrhage transformation and 1-year prognosis.Methods:A retrospective study was conducted to select 752 patients with cerebral infarction who were treated in Beijing Tiantan Hospital,Capital Medical University from December 2018 to December 2019 as the study objects. Personal information and laboratory indicators of the patients were collected including prealbumin, hemoglobin, white blood cell count, etc.Patients were divided into group B1 (<238 mg/L) and group B2 (≥238 mg/L) based on median prealbumin. By inquiry patient's case, NIHSS score (<16 was classified as mild, ≥16 as moderate and severe)and cerebral infarction volume (<20 cm 3 as small infarct, >20 cm 3 as large infarct) were recorded to evaluate the severity of the disease, and whether hemorrhage transformation occurred during hospitalization was recorded. Patients were followed up 1 year after discharge, and prognostic information of patients was recorded, including neurological function recovery (mRS score <3 was classified as good recovery, ≥3 as poor recovery),all-cause case fatality rate, and recurrence of cardio-cerebrovascular events. Normally distributed measurement data were expressed as xˉ±s, non-normally distributed measurement data were expressed as median and quartiles[ M( Q1, Q3)], categorical variable were expressed as ratio and percent(%). Comparison between groups of measurement data were performed by independent sample t test and Mann-Whitney U test. Chi-square test were used on comparison between groups of categorical variable. Single-factor comparison, Spearman correlation analysis and multiple Logistic regression were used to analyze the correlation between prealbumin and other laboratory indicators, cerebral infarction severity, hemorrhage transformation and 1-year prognosis, respectively. Results:The NIHSS score and infarct volume of patients in group B1 were 5(2,10) and 3.18(0.72,18.00) cm 3, and those in group B2 were 3(2,7) and 2.0(0.5,10.0) cm 3, respectively, which were higher in group B1 than in group B2, the differences were statistically significant ( Z=3.85, P<0.001, Z=2.81, P=0.005). The proportion of mRS Score ≥3 in group B1 was 28.8%(107/371), and the all-cause case fatality rate was 7.5%(28/371), both higher than 20.5%(78/381) and 3.1%(12/381) in group B2, with statistical significance ( χ2=7.10, P=0.008, χ2=7.22, P=0.007). Hemorrhage transformation and recurrence of cardio-cerebrovascular events were 13.5%(50/371) and 11.6%(43/371) in group B1 and 9.2% (35/381) and 8.7%(33/381) in group B2, respectively, with no significant difference between the two groups ( χ2=3.45, P=0.063, χ2=1.78, P=0.183). Multivariate logistic regression analysis showed that, after adjusted for potential confounding factors, prealbumin was protective factor of NIHSS ( OR and 95% CI: 0.990(0.984-0.997), P=0.035), poor neurological recovery(mRS≥3) ( OR and 95% CI:0.992(0.988-0.997), P<0.001) and all-cause case fatality rate ( OR and 95% CI:0.991(0.983-0.999), while prealbumin had no significant influence on cardiocerebrovascular recurrence events ( OR and 95% CI: 0.999(0.993-1.005), P=0.729). Conclusion:Prealbumin is significantly associated with the severity of cerebral infarction and poor prognosis 1 year after discharge, and low prealbumin was an independent risk factor for NIHSS score(≥16), poor neurological recovery (mRS≥3) and all-cause case fatality rate.