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Coronary artery disease (CAD) remains a leading global cause of mortality. The expression of small ubiquitin-like modifier 1 (SUMO-1) is reduced in heart failure. However, the mechanisms underlying its modification in CAD remain underexplored. This study sought to identify SUMOylation-related biomarkers and elucidate the potential mechanisms in CAD pathogenesis. This study analyzed three CAD datasets (GSE42148, GSE23561, and GSE121893) alongside 187 SUMOylation-related genes (SRGs). The overlap between differentially expressed genes (DEGs) and SRGs was used to identify differentially expressed SUMOylation-related genes (DE-SRGs). Biomarkers were validated through expression profiling and receiver operating characteristic (ROC) curve analysis. Enrichment and immune infiltration analyses were performed to explore the molecular mechanisms by which these biomarkers influence CAD. A drug-gene interaction network was constructed using the Drug-Gene Interaction database (DGIdb). Single-cell analysis was conducted to identify key cellular players and validate the differential expression of biomarkers across cell types. A total of 12 DE-SRGs were identified in CAD. Among them, SUMO1 and PPARG were validated as biomarkers, with their expression significantly elevated in the CAD group compared to the control group. Single-sample gene set enrichment analysis (ssGSEA) revealed distinct immune cell distributions in CAD, with central memory CD4 + T cells and memory B cells positively correlated with the biomarkers. Gene set enrichment analysis (GSEA) linked these biomarkers to ribosomal activity, olfactory transduction, and other pathways. Single-cell analysis confirmed the expression of SUMO1 and PPARG in endothelial cells, particularly in the CAD group. Additionally, SUMO1 was differentially expressed in cardiomyocytes, exhibiting higher expression in controls. SUMO1 and PPARG were identified as novel SUMOylation-related biomarkers in CAD, suggesting new therapeutic avenues for CAD management.

Nowadays, ultra-wideband (UWB) technology is becoming a new approach to localize keyfobs in the car keyless entry system (KES), because it provides precise localization and secure communication. However, for vehicles the distance ranging suffers from great errors because of none-line-of-sight (NLOS) which is raised by the car. Regarding the NLOS problem, efforts have been made to mitigate the point-to-point ranging error or to estimate the tag coordinate by neural networks. However, it still suffers from some problems such as low accuracy, overfitting, or a large number of parameters. In order to address these problems, we propose a fusion method of a neural network and linear coordinate solver (NN-LCS). We use two FC layers to extract the distance feature and received signal strength (RSS) feature, respectively, and a multi-layer perceptron (MLP) to estimate the distances with the fusion of these two features. We prove that the least square method which supports error loss backpropagation in the neural network is feasible for distance correcting learning. Therefore, our model is end-to-end and directly outputs the localization results. The results show that the proposed method is high-accuracy and with small model size which could be easily deployed on embedded devices with low computing ability.

Coordinating the relationship between “dual carbon” targets and stable economic growth is crucial for promoting high-quality development in China. This study utilizes the coupling coordination model, kernel density estimation, and spatial econometric models to explore the temporal and spatial evolution characteristics and influencing factors of the coupling coordination degree between the promotion of the “dual carbon” targets and stable economic growth in 287 Chinese cities from 2011 to 2021. The results indicate that, in terms of temporal evolution, the promotion of China’s “dual carbon” targets increases yearly, while stable economic growth follows a “year-on-year increase—short-term decline—sustained recovery” pattern with the coupling coordination degree fluctuating upward. Regarding spatial evolution, the coupling coordination degree between the promotion of the “dual carbon” targets and stable economic growth in China presents a “higher in the east, lower in the west” spatial pattern, with varying gradient effects and polarization across the country and its regions. Influencing factors include government intervention, environmental regulations, energy efficiency, financial development, and R&D investment intensity. These findings provide scientific insights for addressing the mutual constraints between “dual carbon” targets and stable economic growth.

Reduced lymphoid enhancer-binding factor 1 (LEF1) expression in patients with adenomyosis during the mid-secretory phase leads to impaired endometrial receptivity, affecting embryo implantation. This study investigated the molecular mechanisms underlying reduced endometrial receptivity in 25 adenomyosis patients and 25 controls. Functional experiments were conducted using human endometrial stromal cells (HESCs) and TERT-immortalized HESCs(T-HESCs), with final validation performed using a mouse model. Western blot and quantitative real-time polymerase chain reaction (RT-qPCR) analyses revealed that patients with adenomyosis showed a marked decrease in LEF1 expression in the stromal cells of the endometrium during the mid-secretory phase. In vitro experiments demonstrated that LEF1 knockdown in stromal cells led to impaired decidualization. Transcriptome sequencing, dual-luciferase reporter assays, and chromatin immunoprecipitation (ChIP) experiments showed that LEF1 could bind to the promoter region of interleukin (IL)-11 and promote its transcription, and IL-11 expression was also found to be downregulated in adenomyosis patients. Overexpression of IL-11 rescued the impaired decidualization caused by decreased LEF1 expression. In the in vitro co-culture model, LEF1/IL-11 knockdown led to a reduction in embryo implantation area, which was partially restored upon IL-11 overexpression. In the adenomyosis mouse model, we observed a decrease in LEF1 expression and a reduction in implantation sites compared to control mice, accompanied by impaired decidualization and receptivity. Notably, supplementation with IL-11 restored the number of implantation sites. The decrease in fertility due to reduced endometrial receptivity in adenomyosis patients is a significant clinical issue in assisted reproductive technology. This research provides insights into one potential molecular mechanism underlying this decreased receptivity, with a specific focus on the reduced expression of LEF1 in the endometrial stromal cells during the mid-secretory phase in adenomyosis patients. Our findings offer new perspectives for clinical strategies to improve endometrial receptivity in patients with adenomyosis, potentially enhancing their chances of successful pregnancy.

Background Premature ovarian insufficiency (POI) is a refractory disease that seriously affects the reproductive health of women and is increasing in incidence and prevalence globally. There is enormous demand to improve fertility in women with POI, while there is still lack of effective therapeutic methods in clinic. Cell-free fat extract (CEFFE) has been reported to contain thousands of active proteins which possess the ability to promote tissue repair in other diseases. In our study, we aimed to observe the efficacy and biosecurity of CEFFE on the repair of ovarian function and fertility of mice with POI and further explore the underlying mechanism. Methods In vivo, POI mice model, established by cyclophosphamide (CTX, 120 mg/kg) and busulfan (BUS, 12 mg/kg), was treated with CEFFE via the tail vein every two days for 2 weeks. Then, the weight of ovaries, estrous cycle and follicle count by H&E staining were measured. The content of AMH, E 2 and FSH in serum was measured by Enzyme-linked immunosorbent assay. Fertility was evaluated by the number of oocytes retrieved, the development of embryos in vitro and the litter size. Biosecurity of parent mice and their pups were examined by body mass and visceral index. The proliferation and apoptosis of cells in ovaries were examined by immunohistochemistry and transmission electron microscopy. Furthermore, the mRNA-Seq of mouse ovarian granulosa cells was performed to explore underlying mechanism of CEFFE. In vitro, KGN cell line and human primary ovarian granulosa cells (hGCs) were treated with 250 μM CTX for 48 h with/without CEFFE. The proliferative ability of cells was detected by cell counting kit-8 assay (CCK-8) and EDU test; the apoptosis of cells was detected by TUNEL and flow cytometry. Results CEFFE recovered the content of AMH, E 2 and FSH in serum, increased the number of follicles and the retrieved oocytes of POI mice ( P  < 0.05). CEFFE contributed to the development of embryos and improved the litter size of POI mice ( P  < 0.05). There was no side effect of CEFFE on parent mice and their pups. CEFFE contributed to the proliferation and inhibited the apoptosis of mouse granulosa cells in ovary, as well as in human ovarian granulosa cells (including KGN cell line and hGCs) ( P  < 0.05). Conclusions The treatment of CEFFE inhibited the apoptosis of granulosa cells and contributed to the recovery of ovarian function, as well as the fertility of mice with POI.

The increasingly severe nocturnal ozone enhancement (NOE) event pollution is widely concerning. Therefore, based on the observed hourly O3 concentrations from 2015 to 2023, this study analyzes the characteristics of NOE events over Putian City. The analysis results show that the frequency of NOE events over Putian City is high, at about 127 days annually, with a high frequency in April and a low frequency in July and August. Most NOE events corresponded to a nocturnal O3 peak concentration (NOP) of <120 μg/m3. Moreover, they mainly occurred between 1:00–3:00 and 7:00. The physicochemical processes over Putian City in April, October, and November 2020 were simulated using the Weather Research and Forecasting (WRF, version 4.3.3) model coupled with the Community Multiscale Air Quality (CMAQ, version 5.4) model. The results suggest that O3 transport, especially horizontal transport from the eastern sea and Zhejiang Province and vertical transport from the upper atmosphere, could be the major cause of NOE events over Putian City. Furthermore, the nocturnal movement of the pollution zone, along with the aggregation of O3 due to weakened dry deposition and the influence of a stable boundary layer obstructed by mountain terrain, significantly influenced the overall O3 concentration. Thus, NOE events over Putian City stem from the interaction among these physicochemical processes. The study results emphasize the importance of O3 control in Putian City and suggest the implementation of strict joint regional control measures for to improve air quality.

Background The precise pathogenesis of poor endometrial receptivity in recurrent implantation failure (RIF) remains unclear. This study was aimed at exploring the effects of different CD44 isoforms in the mid-secretory phase endometrium on endometrial receptivity in women with RIF. Methods Mid-secretory phase endometrial tissue samples were obtained from the following two groups of women who had undergone IVF: (a) 24 patients with RIF and (b) 18 patients with infertility due to tubal obstruction, who had achieved a successful clinical pregnancy after the first embryo transfer in IVF (control group). Identification of differentially expressed CD44 isoforms in endometrial tissues was assessed using immunohistochemistry, qPCR, and western blotting. Effects of overexpression and knockdown of CD44v3 on proliferation and decidualization of immortalized human endometrial stromal cells (T-HESCs) and primary HESCs were investigated by qPCR and western blot analysis. A heterologous coculture system of embryo implantation was constructed to mimic the process of trophoblast invasion during implantation. Results The expression of CD44v3 was significantly higher in the mid-secretory phase of endometrial stromal cells than in the proliferation phase, but was notably lower in RIF patients. Knockdown of CD44v3 significantly downregulated cell proliferation both in T-HESCs and HESCs. The expression of decidualization markers, prolactin (PRL) and insulin like growth factor binding protein-1 (IGFBP1), was notably decreased following the knockdown of CD44v3, whereas the expression of both PRL and IGFBP1 increased after its overexpression in HESCs. Furthermore, the CD44v3-knockdown HESCs displayed significant deficiency in supporting trophoblast outgrowth in a coculture system of embryo implantation; however, overexpression of CD44v3 in HESCs promoted trophoblast outgrowth. Conclusion The reduced expression of CD44v3 suppresses the proliferation and decidualization of HESCs, which might play a pivotal role in poor endometrial receptivity in women with RIF.

Dianthus superbus L. has been extensively studied for its potential medicinal properties in traditional Chinese medicine and is often consumed as a tea by traditional folk. It has the potential to be exploited in the treatment of inflammation, immunological disorders, and diabetic nephropathy. Based on previous studies, this study continued the separation of another subfraction of Dianthus superbus and established reversed-phase/reversed-phase and reversed-phase/hydrophilic (RPLC) two-dimensional (2D) high-performance liquid chromatography (HPLC) modes, quickly separating two C-glycosylflavones, among which 2″-O-rhamnosyllutonarin was a new compound and isomer with 6‴-O-rhamnosyllutonarin. This is the first study to investigate the effects of 2″-O-rhamnosyllutonarin and 6‴-O-rhamnosyllutonarin on cellular glucose metabolism in vitro. First, molecular docking was used to examine the effects of 2″-O-rhamnosyllutonarin and 6″-O-rhamnosyllutonarin on AKT and AMPK; these two compounds exhibited relatively high activity. Following this, based on the HepG2 cell model of insulin resistance, it was proved that both of the 2″-O-rhamnosyllutonarin and 6‴-O-rhamnosyllutonarin demonstrated substantial efficacy in ameliorating insulin resistance and were found to be non-toxic. Simultaneously, it is expected that the methods developed in this study will provide a basis for future studies concerning the separation and pharmacological effects of C-glycosyl flavonoids.

The increasing Ozone (O3) concentration in various regions of China has garnered significant attention, highlighting the need to understand the mechanisms of O3 formation. This study focuses on the source apportionment of O3 in Jilin City during and after the COVID-19 lockdown countermeasure, and also the influence of anthropogenic emissions on O3 concentration. The contributions of different O3 emission sources were quantified using the Weather Research and Forecasting Community Multi-Scale Air Quality (WRF-CMAQ) model in conjunction with the Integrated Source Apportionment Method (ISAM). The results indicate a significant increase in O3 concentrations during the lockdown in Jilin City, which were particularly characterized by long-distance transportation. Transportation is identified as the primary direct source of O3 in Jilin City, with Yongji County contributing the most among the six designated regions. This study highlights variations in the causes and sources of O3 pollution among the different regions of Jilin City. Simply controlling anthropogenic emissions is inadequate for effectively managing O3 pollution and may even worsen the situation. It is more effective to focus on controlling O3’s precursors. These findings improve the understanding of O3 pollution in Jilin City and provide valuable insights for developing O3 control policies. Similarly, this research is applicable to other countries and regions.

Bakground Sepsis/septic shock frequently occurred as a lethal complication in the intensive care unit. Endoplasmic reticulum stress (ERS) leading to the disturbance of cellular proteostasis played an important role in the sepsis-induced multiple organ dysfunction. Previous studies showed that several ERS molecule were involved in. It is not clear which ERS molecule could be competent as prognostic indicators of sepsis. Methods Transcriptomic datasets containing gene expression profiles of sepsis patients and healthy controls were downloaded from the GEO database. Consensus clustering was performed to identify sepsis molecular subtypes associated with ERS. An integrated machine learning approach was conducted to screen potential prognostic markers for sepsis. Results The overactivated ERS-related sepsis subgroup were identified according to higher APACHE II scores and poor prognosis. Further molecular characterization and immune function analysis of this subgroup revealed that overactivated ERS-related sepsis was linked to excessive neutrophil extracellular trap (NET) formation, inflammatory response and pronounced immunosuppression. AHSP, FIS1, REXO2 and SYF2 were identified as key prognostic markers for this sepsis subtype. Their expressions following sepsis and their role in the severity of sepsis were validated by in vivo experiments. Furthermore, a prognostic risk model with the four genes was established as an independent and superior prognostic indicator, outperforming APACHE IV score and cardiovascular insufficiency in predicting outcome for septic patients. Conclusion In summary, four ERS-related genes play an important role in sepsis-induced organ dysfunction, and the ERS-related prognostic model shows great potential as a major forewarning model.