Female-specific cancers seriously affect physical and psychological health of women worldwide. We aimed to elucidate trends in the age-standardized mortality rates (ASMRs) of breast cancer, cervical cancer, uterine cancer, and ovarian cancer in female populations with different socioeconomic statuses in China and in countries with different Human Development Index (HDI). A longitudinal study was performed using the data of cancer death in China and other 39 countries. The mortality rates were standardized with the Segi’s world population. Trends in the mortalities were exhibited by estimated annual percentage change (EAPC). Pearson correlation was used to assess the association between EAPC and HDI. In mainland China, female breast cancer, cervical cancer, uterine cancer, and ovarian cancer accounted for 6.60 %, 4.21 %, 2.50 %, and 2.02 % of cancer death (n = 1,314,040) in women with 1,220,251,032 person-years, respectively. The ASMRs of cervical cancer (EAPC = 3.87 %, P < 0.001) and ovarian cancer (EAPC = 1.81 %, P < 0.001) increased, that of female breast cancer unchanged, whereas that of uterine cancer was extremely higher and rapidly decreased (EAPC = − 7.65 %, P < 0.001), during 2004–2019. The ASMRs of female breast and ovarian cancers were higher in urban and developed regions than in rural and undeveloped regions, in contrast to cervical and uterine cancers. The ASMRs of female breast and ovarian cancers were lower in China than in other countries, in contrast to uterine cancer. The ASMR of cervical cancer decreased, that of uterine cancer increased, in other countries during 2004–2017. EAPCs for the ASMRs of breast and ovarian cancers were inversely correlated to HDI. The ASMRs of cervical and ovarian cancers increased, in contrast to uterine cancer, in China during socioeconomic transition. Trends in the ASMRs of breast and ovarian cancers were inversely associated with HDI. These data help control female-specific cancers.

Despite promising results in myocardial infarction (MI), mesenchymal stem cell (MSC)‐based therapy is limited by cell senescence. N6‐methyladenosine (m6A) messenger RNA methylation has been reported to be closely associated with cell senescence. Nonetheless, its role in the regulation of MSC senescence remains unclear. We examined the role of ALKB homolog 5 (ALKBH5) in regulating MSC senescence and determined whether ALKBH5 downregulation could rejuvenate aged MSCs (AMSCs) to improve their therapeutic efficacy for MI. RNA methylation was determined by m6A dot blotting assay. MSC senescence was evaluated by senescence‐associated β‐galactosidase (SA‐β‐gal) staining. A mouse model of acute MI was established by ligation of the left anterior decedent coronary artery (LAD). Compared with young MSCs (YMSCs), m6A level was significantly reduced but ALKBH5 was greatly increased in AMSCs. Overexpression of ALKBH5 reduced m6A modification and accelerated YMSC senescence. Conversely, ALKBH5 knockdown increased m6A modifications and alleviated AMSC senescence. Mechanistically, ALKBH5 regulated the m6A modification and stability of CDKN1C mRNA, which further upregulated CDKN1C expression, leading to MSC senescence. CDKN1C overexpression ameliorated the inhibition of cellular senescence of ALKBH5 siRNA‐treated AMSCs. More importantly, compared with AMSCs, shALKBH5‐AMSCs transplantation provided a superior cardioprotective effect against MI in mice by improving MSC survival and angiogenesis. We determined that ALKBH5 accelerated MSC senescence through m6A modification‐dependent stabilization of the CDKN1C transcript, providing a potential target for MSC rejuvenation. ALKBH5 knockdown rejuvenated AMSCs and enhanced cardiac function when transplanted into the mouse heart following infarction.

Aortic dissection (AD) represents a critical condition characterised by a tear in the inner lining of the aorta, leading to the leakage of blood into the layers of the aortic wall, posing a significant risk to life. However, the pathogenesis is unclear. In this study, scRNA‐seq was applied to cells derived from aortas of both AD and non‐AD donors (control) to unveil the cellular landscape. ScRNA‐seq data uncover significant cellular heterogeneity in AD aortas. Specifically, we observed an accumulation of CD4⁺ T cells, which contributed to inflammation and cell death, and abnormal collagen formation mediated by fibroblast cells in AD. Moreover, we revealed a greater prevalence of cell death, oxidative stress and senescence in AD aorta cells. Furthermore, we found a decrease in the percentage of vascular stem cells (VSCs), along with a repression in their ability to differentiate into contractile vascular smooth muscle cells (VSMCs). Finally, our data demonstrated that the PDGF signalling pathway was activated in AD. We found that PDGF activation could lead to VSMCs aberrant switch from contractile to synthetic phenotype, which could be ameliorated by PDGF inhibitor. This underscores the potential of the PDGF as a therapeutic target for AD. In summary, our study highlights the cellular heterogeneity and associated injuries within aortas affected by AD, including cell death, oxidative stress, senescence and dysregulation of signalling pathways influencing the aberrant phenotypic switch of VSMCs. These insights offer valuable contributions to understanding the molecular mechanisms underlying AD and present new avenues for therapeutic intervention in this condition.