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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.

Nicotiflorin has demonstrated efficacy in mitigating acute liver injury, and therefore, its potential in treating septic acute kidney injury (AKI) merits further investigation. This study evaluated whether nicotiflorin restores mitochondrial function and reduces oxidative stress in septic AKI mediating the PTEN-induced putative protein kinase 1 (PINK1)/Parkin signaling pathway. Lipopolysaccharide (LPS) was applied to replicate septic AKI in C57BL/6 mice and NRK-52E cells, which were later treated with nicotiflorin. Renal function was assessed through biochemical markers, histopathology, and immunofluorescence. The impact of nicotiflorin on cell viability, apoptosis, and mitochondrial function was analyzed using cell counting kit 8 assay and flow cytometry. Mtphagy and Lyso staining was utilized to evaluate the effect of nicotiflorin on mitophagy in LPS-induced cells. Molecularly, Western blot was employed to quantify protein expressions of genes related to apoptosis, mitophagy and oxidative stress and . Nicotiflorin treatment significantly improved renal dysfunction, kidney damage, reduced levels of apoptosis-related proteins, increased expressions of PINK1, Parkin, and LC3II/LC3I, and decreased expression of p62 in LPS-induced mice. In NRK-52E cells, nicotiflorin abrogated LPS-triggered reduction in cell viability, increase in apoptosis, elevation in ROS and mitochondrial mass, reduction in mitochondrial membrane potential, upregulation of apoptotic proteins, downregulated NF-E2-related factor-2 (Nrf2), PINK1, Parkin and LC3II/LC3I, and increased expressions of kelch-like ECH-associated protein 1 (KEAP1) and p62. Nicotiflorin attenuates mitochondrial dysfunction and oxidative stress in septic AKI PINK1/Parkin signaling pathway, suggesting its potential as a therapeutic agent for septic AKI.

Oleanolic acid (OA), asiatic acid (AA), and maslinic acid (MA) are ubiquitous isomeric triterpene phytochemicals with many pharmacological effects. To improve their application value, we used lipopolysaccharide (LPS) to induce RAW264.7 cells and studied the differences in the anti-inflammatory effects of the triterpenes according to their structural differences. MTT, Griess, and immunofluorescence assays, ELISA, flow cytometry, and Western blotting, were performed. The release of LPS-induced pro-inflammatory mediators, such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), and interleukin (IL-6), was significantly inhibited by OA, AA, and MA at the same concentration, and AA and MA promoted the production of anti-inflammatory factor IL-10. OA, AA, and MA inhibited LPS-induced NF-κB nuclear translocation in RAW264.7 cells. OA and AA inhibited the phosphorylation of ERK1/2, P38, and JNK1/2 in LPS-stimulated RAW264.7 cells. Moreover, OA increased LPS-induced Nrf2 expression and decreased Keap1 expression in RAW264.7 cells. OA, AA, and MA inhibited LPS-stimulated intracellular reactive oxygen species (ROS) production and alleviated mitochondrial membrane potential depletion. Overall, our data suggested that OA, AA, and MA exhibited significant anti-inflammatory effects in vitro. In particular, OA and AA take effects through the MAPKs, NF-κB, and Nrf2 signaling pathways.

Based on the observations by the Parker Solar Probe (PSP) during its encounter phases of approaching the Sun, I. C. Jebaraj et al. found that fundamental–harmonic (F-H) pairs constitute a majority of interplanetary (IP) type III radio bursts. In the present Letter, spectral characteristics of the IP F-H pairs are identified and analyzed further. The observations were made with the Radio Frequency Spectrometer (RFS) experiment on the PSP spacecraft in its encounter phase from the first to the ninth orbit as it traveled from 0.17 to 0.074 au from the Sun. The result shows that the occurrence rate of F-H pairs rises significantly with the rise in the number of IP type III radio bursts detected by the PSP or the enhancement in the time resolution of the RFS instrument. In particular, we compare the relationship between F and H spectral characteristics, such as the frequency-drift rate, emission intensity, relative bandwidth, duration, and fine structure. The results will be helpful for us to understand the physics underlying the generation and evolution of the IP F-H pairs as well as other IP type III radio bursts.

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.

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.

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.

The Parker Solar Probe (PSP) provides us with an unprecedentedly close approach to the observation of the Sun and hence the possibility of directly understanding the elementary process that occurs on the kinetic scale of particles' collective interaction in solar coronal plasmas. We report a type of weak solar radio burst (SRB) that was detected by PSP when it passed a low-density magnetic channel during its second encounter phase. These weak SRBs have a low starting frequency of ∼20 MHz and a narrow frequency range from a few tens of MHz to a few hundred kHz. Their dynamic spectra display a strongly evolving feature of the intermediate relative drift rate decreasing rapidly from above 0.01 s−1 to below 0.01 s−1. Analyses based on common empirical models of solar coronal plasmas indicate that these weak SRBs originate from a heliocentric distance of ∼1.1–6.1 R S (the solar radius), a typical solar wind acceleration region with a low-β plasma, and that their sources have a typical motion velocity of ∼v A (Alfvén velocity) obviously lower than that of the fast electrons required to effectively excite SRBs. We propose that solitary kinetic Alfvén waves with kinetic scales could be responsible for the generation of these small-scale weak SRBs, called solitary wave radiation.

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.