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.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Intracranial atherosclerotic stenosis （ICAS） is an important cause of stroke worldwide， and abnormalities in lipid metabolism are major risk factors for its development and progression. Statins as lipid-lowering drugs can stabilize atherosclerotic plaques and prevent their rupture， but approximately 60% of statin users fail to achieve the goal of low-density lipoprotein cholesterol （LDL-C） recommended in guidelines， and statins are associated with the adverse effects such as drug resistance and abnormal liver function. Numerous studies have confirmed that proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors can significantly reduce the level of LDL-C and the incidence rate of atherosclerosis-associated cardiovascular and cerebrovascular events and stabilize or even reverse atherosclerotic plaques， but with limited application in ICAS. This article reviews the mechanism of action of PCSK9 inhibitors， their therapeutic efficacy in intracranial atherosclerotic stenosis， and related research advances.

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.

Mitochondria are important organelles which produce the energy required to maintain cell activity.They can produce energy through oxidative phosphorylation(OXPHOS),tricarboxylic acid(TCA)cycle and other pathways,and play an essential role in cell metabolism and many physiological processes.However,mitochondrial dysfunction is associated with neurodegenerative diseases such as Alzheimer's disease(AD).Previous studies have confirmed that mitochondrial oxidative phosphorylation-related proteins,membrane transporters,fusion and fission proteins can affect mitochondrial function and participate in the pathophysiological process of AD via mechanisms such as oxidative stress injury.Therefore,this article reviews the involvement of mitochondrial proteins and its dysfunction in the pathogenesis of AD and the possibility of treating AD by regulating mitochondrial proteins and its functions.

Mitochondria are important organelles which produce the energy required to maintain cell activity.They can produce energy through oxidative phosphorylation(OXPHOS),tricarboxylic acid(TCA)cycle and other pathways,and play an essential role in cell metabolism and many physiological processes.However,mitochondrial dysfunction is associated with neurodegenerative diseases such as Alzheimer's disease(AD).Previous studies have confirmed that mitochondrial oxidative phosphorylation-related proteins,membrane transporters,fusion and fission proteins can affect mitochondrial function and participate in the pathophysiological process of AD via mechanisms such as oxidative stress injury.Therefore,this article reviews the involvement of mitochondrial proteins and its dysfunction in the pathogenesis of AD and the possibility of treating AD by regulating mitochondrial proteins and its functions.

Diminished ovarian reserve (DOR) is a common reproductive endocrine disease in women, which is an important factor leading to the decline of female fertility. The number and quality of oocytes in DOR women gradually decrease with age, which leads to the decline of fertility in women. Mitochondrial dysfunction is an important cause of oocyte quality decline. In recent years, studies have found that mitophagy, as an important mechanism of self-repair and metabolic balance in cells, is closely related to oocyte development. This article focuses on the regulation of mitochondrial DNA copy number and mutation, ATP content, mitochondrial reactive oxygen species content, mitochondrial membrane potential changes on mitophagy, and the effects on oocyte development and the regulation of drugs on oocyte mitophagy.

The importance of question bank construction in medical education has been well proved.However,there are still some weaknesses in the clinical teaching assessment question bank,including the inconsistency be-tween assessment and clinical practice,the lack of coherence in question bank updates,and the mismatch be-tween proposition and student learning stage.To address these issues,this article explores a teaching model which connects flipped classroom with student independent proposition and analyzes the advantages of applying flipped classroom to question bank construction.The connection between the two effectively established a regular updating mechanism for question banks,thus improve the construction of question banks in current medical education.It may support the capacity building of students' self-oriented and regulated learning and improve the quality of teaching assessment.

Diminished ovarian reserve (DOR) is a common reproductive endocrine disease in women, which is an important factor leading to the decline of female fertility. The number and quality of oocytes in DOR women gradually decrease with age, which leads to the decline of fertility in women. Mitochondrial dysfunction is an important cause of oocyte quality decline. In recent years, studies have found that mitophagy, as an important mechanism of self-repair and metabolic balance in cells, is closely related to oocyte development. This article focuses on the regulation of mitochondrial DNA copy number and mutation, ATP content, mitochondrial reactive oxygen species content, mitochondrial membrane potential changes on mitophagy, and the effects on oocyte development and the regulation of drugs on oocyte mitophagy.

Objective:To investigate the mechanism of human placenta derived mesenchymal stem cells (hPMSCs) in the inhibition of TNF-α secretion in CD4 + IFN-γ + T cells (Th1) through CD73/nuclear factor-erythroid 2-related factor 2(Nrf2) pathway to reduce liver injury in mice with graft versus-host disease (GVHD). Methods:Flow cytometry (FCM) was used to analyze the expression of TNF-α in Th1 cells and the expression of PD-1 on CD4 + IFN-γ + TNF-α + T cells (TNF-α + Th1 cells) isolated from peripheral blood and liver tissues of mice with GVHD. Hematoxylin-hosin (HE) staining, Masson staining and immunofluorescence staining were used to observe the pathological changes in liver tissues of GVHD mice in each group. HE staining was also used to observe the pathological changes in skin and lung tissues of GVHD mice. A nonconditional protocol to induce the differentiation of peripheral blood mononuclear cells (PBMCs) into Th1 cells in vitro was established. The proportion of TNF-α + Th1 cells and the mean fluorescence intensity (MFI) of Nrf2 and phosphorylated nuclear factor-kappa B (p-NF-κB) in this T cell subgroup were detected. Results:Compared with the normal control group, the proportion of TNF-α + Th1 cells and the expression of PD-1 on this T cells in peripheral blood and liver tissues of mice in the GVHD high group increased significantly ( P<0.01). The proportion of TNF-α + Th1 cells in peripheral blood and liver tissues decreased after hPMSCs treatment ( P<0.001), but the expression of PD-1 on this T cell subset was promoted in peripheral blood and liver tissues ( P<0.01, P<0.001). However, the intervention effects of shCD73 on TNF-α + Th1 cells in peripheral blood and liver tissues were significantly weakened ( P<0.05, P<0.01). Liver histopathological analysis showed that the proportion of TNF-α + Th1 cells in liver was positively correlated with Suzuki′s score, collagen area and the MFI of α-SMA ( P<0.001). Similarly, histopathological analysis of skin and lung tissues also showed that the proportion of TNF-α + Th1 cells in peripheral blood was positively correlated with skin Marina score and lung Shukai Qiao score ( P<0.001). In vitro experiment also showed that hPMSCs down-regulated the proportion of TNF-α + Th1 cells ( P<0.01) and up-regulated the expression of PD-1 on them ( P<0.05). Further analysis showed that hPMSCs could enhance the MFI of Nrf2 ( P<0.05) and weaken the MFI of p-NF-κB ( P<0.01) in TNF-α + Th1 cells. Conclusions:hPMSCs could up-regulate the expression of PD-1 through CD73/Nrf2 pathway to inhibit the formation of TNF-α + Th1 cells, thereby alleviating liver injury in GVHD mice.