Ningbo Municipal People's Government

BackgroundAdvanced maternal age (AMA) increases pregnancy risk. However, uterine‐specific mechanisms independent of oocyte and embryo quality remain poorly defined. This study aimed to characterise the decidual microenvironment in women with AMA to identify key pathological changes and regulatory pathways.Methods and resultsThrough integrated histology, organoid modelling, and high‐resolution scRNA‐seq of first‐trimester decidua from women of AMA and controlled reproductive age, we uncovered a pathologically remodelled decidual microenvironment characterised by aberrant cellular states and pathological differentiation pathways, leading to a pro‐fibrotic state and accompanied by immune cell dysfunction, and disrupted intercellular communication in the AMA decidua. Central to this pathology was hyperactivated TGF‐β signalling, driving fibroblast‐to‐myofibroblast transition and extracellular matrix overproduction, thereby fuelling fibrosis. Aberrant TGF‐β further impaired decidual stromal cell (DSC) differentiation, leading to the failure of the essential mesenchymal‐to‐epithelial transition. We identified PRR15 as a novel DSC‐specific regulator that is markedly suppressed in AMA. PRR15 deficiency unleashed hyperactive TGF‐β/SMAD signalling, directly causing decidualisation failure, enhanced fibrosis, and aborted DSC differentiation. Epithelial–mesenchymal transition and immune cell reprogramming towards pro‐fibrotic transcriptional signatures further amplify the fibrotic pathology.ConclusionThis study established the aged decidual microenvironment, orchestrated by dysregulated TGF‐β signalling and PRR15 loss, as a critical independent determinant of reproductive failure in AMA. Thus, it unveils novel diagnostic and therapeutic targets and strategies.Key pointsWe provide the first single‐cell atlas of the human decidua in advanced maternal age (AMA).A novel PRR15‐TGF‐β axis is identified, where PRR15 loss drives stromal fibrosis and decidualisation failure.This study reveals that AMA‐associated uterine fibrosis begins in the first trimester, shifting focus to maternal factors.

Technical limitations in spatial and single-cell omics sequencing pose challenges for capturing and describing multimodal information at the spatial scale. To address this, we develop SIMO, a computational method designed for the Spatial Integration of Multi-Omics datasets through probabilistic alignment. Unlike previous tools, SIMO not only integrates spatial transcriptomics with single-cell RNA-seq but expands beyond, enabling integration across multiple single-cell modalities, such as chromatin accessibility and DNA methylation, which have not been co-profiled spatially before. We benchmark SIMO on simulated datasets, demonstrating its high accuracy and robustness. Further application on biological datasets reveals SIMO’s ability to detect topological patterns of cells and their regulatory modes across multiple omics layers. Through comprehensive analysis of real-world data, SIMO uncovers multimodal spatial heterogeneity, offering deeper insights into the spatial organization and regulation of biological molecules. These findings position SIMO as a powerful tool for advancing spatial biology by revealing previously inaccessible multimodal insights.

BackgroundCauses of death (CODs) in patients with gastric cancer (GC) need to be studied. We examined the cancer-specific and non-cancer deaths among patients diagnosed with GC from 1975 to 2019.Material/MethodsWe obtained medical records from the Surveillance, Epidemiology, and End Results (SEER) database. We used SEER*Stat software to calculate standardized mortality ratios (SMRs) for specific CODs and performed a competing risk analysis to evaluate the cumulative mortality of specific CODs.ResultsThe final study cohort included 42 813 patients with GC, with a mean age at diagnosis of 67.7 years. As the end of 2021, a total of 36 924 (86.2%) patients died. Of these deaths, 24 625 (66.7%) were from GC, 6513 (17.6%) were from other types of cancers, and 5786 (15.7%) were from non-cancer causes. The most prevalent non-cancer CODs were heart diseases (2104; 5.7%), cerebrovascular diseases (501; 1.4%), and pneumonia/influenza (335; 0.9%). Among patients who survived over 5 years, non-cancer causes surpassed GC as the main CODs. Patients with GC had a higher risk of dying from many non-cancer causes than expected in the general population, particularly from suicide (SMR, 3.03; 95% CI, 2.35–3.85) and septicemia (SMR, 2.93; 95% CI, 2.51–3.4). The competing risk analysis showed that the cumulative mortality of GC gradually declined with a more recent diagnosis.ConclusionsAlthough GC was the leading COD among patients with GC, non-cancer CODs accounted for a substantial number of deaths. These findings provide useful guidance on potential death risks among patients with GC.

Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder, manifested as oxidative stress, lipid accumulation, and inflammation of the liver. Tetrastigma hemsleyanum leaves (THL), which are rich in flavonoids and phenolic acids, have good anti-inflammatory, antioxidant, and hepatoprotective effects. However, it is unknown whether THL extracts can improve NAFLD and the underlying mechanisms are unknown. Hence, this study was designed to investigate the effects of THL extracts on NAFLD and perform a preliminary inquiry into the underlying mechanism based on the gut-liver axis. The results showed that THL extracts could reverse NAFLD-related oxidative stress, lipid accumulation, and inflammation. Additionally, the protective effect of THL extracts on the gut includes the maintenance of the intestinal barrier and the regulation of gut microbiota, which may be one of the mechanisms by which THL improves NAFLD. To be specific, in our study, THL extracts alleviated hepatic lipid accumulation and oxidative stress by regulating the expression of lipid synthesis/catabolism and the oxidative stress genes (SREBP-1c/ACC-1/PPAR-α/PPAR-γ/Keap1/Nrf2). In addition, THL extracts reduced damage to the intestinal barrier (ZO-1/Mucin2/occludin) and increased the relative abundance of Lactobacillales, Ruminococcaceae, and Bifidobacteriales in NAFLD mice. In short, THL extracts alleviated NAFLD-related oxidative stress, lipid accumulation, and inflammation in NAFLD mice which may be via the gut-liver axis (gut barrier integrity and gut microbiota).

The three rights separation reform (TRSR) has laid a concrete foundation institutionally to guide the well-ordered transfer of farmland and promoting the development of urbanization. With the new economics of labour migration (hereinafter referred to as the NELM) theory as the analytic basis, this empirical research investigates the potential ramifications of off-farm employment on land efficiency with household-based survey data from four provinces in China after TRSR. Unlike existing studies, we delve into how the effects are manifested differently among the types of off-farm employment by adopting an ordinary least squares (OLS) model and a two-stage least squares (2SLS) estimator. It provides evidence that migration positively affect land efficiency significantly, whereas a negative impact of local off-farm employment on land efficiency is observed, which distinct this study from previous findings. From the perspective of policy-making, land administrators should realize that off-farm employment differentiation is an important factor affecting land efficiency, and therefore needs to be fully considered in policy-making. Meanwhile, the establishment of local labor markets and favorable policies that stimulate productive technologies are needed.

Background: Rhoifolin is a plant flavonoid known to have antioxidant and anti-inflammatory properties. This study was taken to identify the effect of rhoifolin on Spinal cord injury (SCI) in a rat model. Methods: Motor function of SCI rats was carried out by using in Basso, Beattie and Bresnahan test. Expression levels of different proteins such as IL-1β, IL-6, TNF-α, NF-κB p65, p-IκB-α, p38MAPK, caspase-3 and caspase-9 were carried out by using western blotting analysis. The Concentration of proteins was determined by using Bradford’s method. Estimating of Glutathione (GSH), Glutathione peroxidase (GPx) and Superoxide dismutase (SOD) was carried out by using commercially available kit. Result: Rhoifolin was tested at 20 and 40 mg/kg doses and showed a significant improvement in the motor function of SCI rats in Basso, Beattie and Bresnahan test. Moreover, rhoifolin treatment also attenuated pro-inflammatory cytokine levels such as IL-1β, IL-6 and TNF-α. The NF-κB pathway showed a significant attenuation as evident in the significant downregulation of the NF-κB p65 and p-IκB-α levels. In addition, rhoifolin treatment also caused a significant reduction in oxidative stress, as evident from changes in intracellular levels of Glutathione, GPx, MDA and SOD in the articular cartilage tissue. Further, we also tested rhoifolin for its effect on the apoptotic pathway by estimating the intracellular levels of p38MAPK, caspase-3 and caspase-9. The current results show that rhoifolin has a neuroprotective in SCI rat model.