A metabolomics discrimination-based strategy for screening the antithrombin active markers of perilla seeds: A natural oil crop.

Natural crops oil with high nutritional value has gradually attracted attention. Perilla seeds are regarded as a source of functional edible oil in America, Asia and European countries due to its abundant nutrients. In this research, samples were extracted by different polarity solvents and evaluated their thrombin inhibition activities in vitro. Metabolomics combined with chemometrics revealed the antithrombin active markers of perilla seeds. The enzyme kinetics and molecular docking results were useful in clarifying their inhibition of thrombin. The orthogonal experimental design was applied to optimize the extraction process of six antithrombin active markers from perilla seeds. The results showed that rosmarinic acid, luteolin, luteolin-7-O-glucoside, α-linolenic acid, linoleic acid, and oleic acid were screened out as functional and active markers. Besides, perilla seeds as a natural oil crop had the potential of antithrombin. It can also be applied in the food field because of its nutraceutical functions. Metabolomics combined with chemometrics will facilitate the discovery of functional, active markers in perilla seeds, which is conducive to accurate quality control.

Neuroprotective effects of Jie-du-huo-xue decoction on microglia pyroptosis after cerebral ischemia and reperfusion--From the perspective of glial-vascular unit.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke poses a serious risk to public health and quality of life. Jie-Du-Huo-Xue decoction (JDHXD) is a classical and well-known Chinese formula for stroke treatment, but the pharmacological mechanism is still unclear. AIM OF THE STUDY: This study aims to investigate the mechanism underlying microglial pyroptosis and polarization, as well as the potential efficacy of JDHXD against cerebral ischemia-reperfusion injury (CIRI). MATERIALS AND METHODS: Models of CIRI were established by the middle cerebral artery occlusion/reperfusion (MCAO/R) method in rats. In the first stage, 36 SD rats were randomly divided into sham group, I/R group, JDHXD-L group (5.36 g/kg/day), JDHXD-M group (10.71 g/kg/day), JDHXD-H group (21.42 g/kg/day), and positive drug edaravone group. The effectiveness of JDHXD on CIRI was confirmed by neurological function testing and cerebral infarct measuring. The best dose (JDXHD-M) was subsequently chosen to perform the tests that followed. In the second stage, 36 SD rats were randomly divided into the sham group, the I/R group, and the JDHXD-M group. Detection of nerve damage using Nissl staining, proteins of pyroptosis, Iba-1, and NeuN expressions were detected by western blotting, and proteins of microglial pyroptosis and M1/M2 phenotypic polarization were detected by immunofluorescence. RESULTS: In rats after CIRI, JDHXD significantly reduced neurological impairment and cerebral infarction. In addition, JDHXD facilitated the M1-to-M2 transition of microglia in order to minimize neuroinflammation and improve anti-inflammatory repair. In addition, JDXHD inhibited microglial pyroptosis by blocking the cleavage of caspase-1 P10 and gasdermin D, hence reducing neuronal damage and enhancing neuronal survival following reperfusion. Interestingly, JDHXD also demonstrated a protective effect on the glial-vascular unit (GVU). CONCLUSIONS: Our investigation demonstrated that JDHXD exerted a GVU-protective effect on CIRI rats by decreasing neuroinflammation-associated microglial pyroptosis, suppressing microglial M1 activation, and promoting microglial M2 activation.

Low-molecular weight sulfated marine polysaccharides: Promising molecules to prevent neurodegeneration in mucopolysaccharidosis IIIA?

Mucopolysaccharidosis IIIA is a hereditary disease caused by mutations in the sulfamidase enzyme that participates in catabolism of heparan sulfate (HS), leading to HS fragment accumulation and multisystemic failure. No cure exists and death occurs around the second decade of life. Two low molecular weight highly sulfated compounds derived from marine diabolican and infernan exopolysaccharides (A5_3 and A5_4, respectively) with heparanase inhibiting properties were tested in a MPSIIIA cell line model, resulting in limited degradation of intracellular HS. Next, we observed the effects of intraperitoneal injections of the diabolican derivative A5_3 from 4 to 12 weeks of age on MPSIIIA mice. Brain metabolism and microstructure, levels of proteins and genes involved in MPSIIIA brain pathophysiology were also investigated. 1H-Magnetic Resonance Spectroscopy (MRS) indicated deficits in energetic metabolism, tissue integrity and neurotransmission at both 4 and 12 weeks in MPSIIIA mice, with partial protective effects of A5_3. Ex-vivo Diffusion Tensor Imaging (DTI) showed white matter microstructural damage in MPSIIIA, with noticeable protective effects of A5_3. Protein and gene expression assessments displayed both pro-inflammatory and pro-apoptotic profiles in MPSIIIA mice, with benefits of A5_3 counteracting neuroinflammation. Overall, derivative A5_3 was well tolerated and was shown to be efficient in preventing brain metabolism failure and inflammation, resulting in preserved brain microstructure in the context of MPSIIIA.

Association of carbohydrate intake from different sources with all-cause and cardiovascular mortality among chronic kidney disease populations: assessment of 1999-2018 National Health and Nutrition Examination Survey participation.

This study analysed the data from the NHANES (1999-2018) to examine how different sources of carbohydrate intake affected the all-cause and cardiovascular mortality of 11,302 chronic kidney disease (CKD) patients. The data were adjusted for other factors using various methods. The results showed that CKD patients (stages 1-2 and 3-5) who consumed more carbohydrates from whole grains, fruits, vegetables and less carbohydrates from fruit juice or sauces had lower mortality rates. Replacing fat intake with carbohydrates from whole grains (HR = 0.86[0.78-0.95]), fruits (raw) (HR = 0.79[0.70-0.88]) and non-starchy vegetables (HR = 0.82[0.70-0.96]), but not protein intake, was linked to lower all-cause mortality. The fibre content in carbohydrates might partly account for the benefits of selected carbohydrate intake. This study provided practical recommendations for optimising the carbohydrate sources in CKD patients.

Functional brain network identification and fMRI augmentation using a VAE-GAN framework.

Recently, deep learning models have achieved superior performance for mapping functional brain networks from functional magnetic resonance imaging (fMRI) data compared with traditional methods. However, due to the lack of sufficient data and the high dimensionality of brain volume, deep learning models of fMRI tend to suffer from overfitting. In addition, existing methods rarely studied fMRI data augmentation and its application. To address these issues, we developed a VAE-GAN framework that combined a VAE (variational auto-encoder) with a GAN (generative adversarial net) for functional brain network identification and fMRI augmentation. As a generative model, the VAE-GAN models the distribution of fMRI so that it enables the extraction of more generalized features, and thus relieve the overfitting issue. The VAE-GAN is easier to train on fMRI than a standard GAN since it uses latent variables from VAE to generate fake data rather than relying on random noise that is used in a GAN, and it can generate higher quality of fake data than VAE since the discriminator can promote the training of the generator. In other words, the VAE-GAN inherits the advantages of VAE and GAN and avoids their limitations in modeling of fMRI data. Extensive experiments on task fMRI datasets from HCP have proved the effectiveness and superiority of the proposed VAE-GAN framework for identifying both temporal features and functional brain networks compared with existing models, and the quality of fake data is higher than those from VAE and GAN. The results on resting state fMRI of Attention Deficit Hyperactivity Disorder (ADHD)-200 dataset further demonstrated that the fake data generated by the VAE-GAN can help improve the performance of brain network modeling and ADHD classification.

Design, synthesis, and anti-tumor activity of derivatives of ring A and C-28 of asiatic acid.

Based on computer-aided drug design (CADD), the active groups of the known active small molecule compounds that can bind to EGFR target protein were analyzed through the molecular docking method. Then, 12 novel asiatic acid derivatives were synthesized by introducing active groups at ring A and C-28 positions of asiatic acid. The structures of these novel compounds were determined by NMR and MS. Furthermore, the anti-tumor activities of these derivatives on human lung cancer cells (A549) and human breast cancer cells (MCF-7) were evaluated by MTT assay. In conclusion, compounds I4 and II3 have stronger anti-cancer activity than parent compounds, the activities were stronger than gefitinib and comparable to afatinib, which may be potential candidate compounds for tumor therapy.

Three-dimensional ultrasound-based radiomics nomogram for the prediction of extrathyroidal extension features in papillary thyroid cancer.

Purpose: To develop and validate a three-dimensional ultrasound (3D US) radiomics nomogram for the preoperative prediction of extrathyroidal extension (ETE) in papillary thyroid cancer (PTC). Methods: This retrospective study included 168 patients with surgically proven PTC (non-ETE, n = 90; ETE, n = 78) who were divided into training (n = 117) and validation (n = 51) cohorts by a random stratified sampling strategy. The regions of interest (ROIs) were obtained manually from 3D US images. A larger number of radiomic features were automatically extracted. Finally, a nomogram was built, incorporating the radiomics scores and selected clinical predictors. Receiver operating characteristic (ROC) curves were performed to validate the capability of the nomogram on both the training and validation sets. The nomogram models were compared with conventional US models. The DeLong test was adopted to compare different ROC curves. Results: The area under the receiver operating characteristic curve (AUC) of the radiologist was 0.67 [95% confidence interval (CI), 0.580-0.757] in the training cohort and 0.62 (95% CI, 0.467-0.746) in the validation cohort. Sixteen features from 3D US images were used to build the radiomics signature. The radiomics nomogram, which incorporated the radiomics signature, tumor location, and tumor size showed good calibration and discrimination in the training cohort (AUC, 0.810; 95% CI, 0.727-0.876) and the validation cohort (AUC, 0.798; 95% CI, 0.662-0.897). The result suggested that the diagnostic efficiency of the 3D US-based radiomics nomogram was better than that of the radiologist and it had a favorable discriminate performance with a higher AUC (DeLong test: p < 0.05). Conclusions: The 3D US-based radiomics signature nomogram, a noninvasive preoperative prediction method that incorporates tumor location and tumor size, presented more advantages over radiologist-reported ETE statuses for PTC.

Portraying the dark side of endogenous IFN-λ for promoting cancer progression and immunoevasion in pan-cancer.

BACKGROUND: IFN-λ has been shown to have a dual function in cancer, with its tumor-suppressive roles being well-established. However, the potential existence of a negative ''tumor-promoting'' effect of endogenous IFN-λ is still not fully understood. METHODS: We conducted a comprehensive review and analysis of the perturbation of IFN-λ genes across various cancer types. Correlation coefficients were utilized to examine the relationship between endogenous IFN-λ expression and clinical factors, immune cell infiltration, tumor microenvironment, and response to immunotherapy. Genes working together with IFN-λ were obtained by constructing the correlation-based network related to IFN-λ and the gene interaction network in the KEGG pathway and IFN-λ-related genes obtained from the networks were integrated as candidate markers for the prognosis model. We then applied univariate and multivariate COX regression models to select cancer-specific independent prognostic markers associated with IFN-λ and to investigate risk factors for these genes by survival analysis. Additionally, computational methods were used to analyze the transcriptome, copy number variations, genetic mutations, and methylation of IFN-λ-related patient groups. RESULT: Endogenous expression of IFN-λ has been linked to poor prognosis in cancer patients, with the genes IFN-λ2 and IFN-λ3 serving as independent prognostic markers. IFN-λ acts in conjunction with related genes such as STAT1, STAT2, and STAT3 to affect the JAK-STAT signaling pathway, which promotes tumor progression. Abnormalities in IFN-λ genes are associated with changes in immune checkpoints and immune cell infiltration, which in turn affects cancer- and immune-related pathways. While there is increased immune cell infiltration in patients with IFN-λ expression, this does not improve survival prognosis, as T-cell dysfunction and an inflammatory environment are also present. The amplification of IFNL2 and IFNL3 copy number variants drives specific endogenous expression of IFN-λ in patients, and those with this specific expression have been found to have more mutations in the TP53 gene and lower levels of DNA methylation. CONCLUSION: Our study integrated multi-omics data to provide a comprehensive insight into the dark side of endogenous IFN-λ, providing a fundamental resource for further discovery and therapeutic exploration in cancer.

Broadband frequency modulation signal downconversion using a monolithic integrated mutual injection laser.

We propose a new, to the best of our knowledge, broadband signal downconversion scheme implemented by a monolithic integrated mutual injection laser. A mathematical derivation, simulation, and experimental verification are carried out. Because the period-one oscillation frequency can be selectively operated on a large scale by controlling the current on the integrated laser, the tuning downconversion range is realized without changing the experimental equipment. The experiment verifies that the downconversion of the linear frequency modulation signal with a bandwidth of 0.5 GHz from the center frequency of 18.75 to 0.85 GHz, and the spurious-free dynamic range (SFDR) has reached 71.7d B/H z 2/3. Compared with the scheme based on discrete components, the system has no electric local oscillator or external modulator, which provides a method for radar signal downconversion.

Vibration rejection of phased array telescope systems via disturbance-propagation-characteristics-based feedforward control.

Vibration rejection is one of the key techniques to stabilize the line of sight (LOS) for phased array telescope systems. Conventionally, feedback control based on image sensors is mainly used to correct the tip/tilt errors caused by disturbances and to keep the LOS stable. However, it is restricted by the sampling rate and time delay of image sensors, leading to a limited closed-loop bandwidth. Disturbances in the middle and high frequencies are hard to suppress. In this paper, disturbance-propagation-characteristics-based feedforward control is proposed to overcome these problems. A theoretical imaging model of the phased array telescope is developed to analyze the LOS disruption caused by disturbance. In addition, to improve the disturbance suppression bandwidth and correction accuracy of the system, the disturbance propagation characteristics of the phased array telescope system are analyzed. Combined with the disturbance feedforward, targeted compensation is achieved for the sub-apertures. Finally, a comparative experiment is carried out based on the self-developed Fizeau phased array telescope system to verify the superiority of the proposed method.

The role of lactoferrin in bone remodeling: evaluation of its potential in targeted delivery and treatment of metabolic bone diseases and orthopedic conditions.

Lactoferrin (Lf) is a multifunctional protein that is synthesized endogenously and has various biological roles including immunological regulation, antibacterial, antiviral, and anticancer properties. Recently, research has uncovered Lf's critical functions in bone remodeling, where it regulates the function of osteoblasts, chondrocytes, osteoclasts, and mesenchymal stem cells. The signaling pathways involved in Lf's signaling in osteoblasts include (low density lipoprotein receptor-related protein - 1 (LRP-1), transforming growth factor ß (TGF-ß), and insulin-like growth factor - 1 (IGF-1), which activate downstream pathways such as ERK, PI3K/Akt, and NF-κB. These pathways collectively stimulate osteoblast proliferation, differentiation, and mineralization while inhibiting osteoclast differentiation and activity. Additionally, Lf's inhibitory effect on nuclear factor kappa B (NF-κB) suppresses the formation and activity of osteoclasts directly. Lf also promotes chondroprogenitor proliferation and differentiation to chondrocytes by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt)signaling pathways while inhibiting the expression of matrix-degrading enzymes through the suppression of the NF-κB pathway. Lf's ability to stimulate osteoblast and chondrocyte activity and inhibit osteoclast function accelerates fracture repair, as demonstrated by its effectiveness in animal models of critical-sized long bone defects. Moreover, studies have indicated that Lf can rescue dysregulated bone remodeling in osteoporotic conditions by stimulating bone formation and suppressing bone resorption. These beneficial effects of Lf on bone health have led to its exploration in nutraceutical and pharmaceutical applications. However, due to the large size of Lf, small bioactive peptides are preferred for pharmaceutical applications. These peptides have been shown to promote bone fracture repair and reverse osteoporosis in animal studies, indicating their potential as therapeutic agents for bone-related diseases. Nonetheless, the active concentration of Lf in serum may not be sufficient at the site requiring bone regeneration, necessitating the development of various delivery strategies to enhance Lf's bioavailability and target its active concentration to the site requiring bone regeneration. This review provides a critical discussion of the issues mentioned above, providing insight into the roles of Lf in bone remodeling and the potential use of Lf as a therapeutic target for bone disorders.

Characterization of the Sensory Properties and Quality Components of Huangjin Green Tea Based on Molecular Sensory-Omics.

Huangjin green tea (HJC) is one of the most famous regional green teas in China, and has gained attention for its unique flavor. Research on HJC has focused mainly on the synthesis of L-theanine, with fewer studies concentrating on sensory characteristics. In this study, molecular sensory science techniques, including color analysis, gas chromatography-ion mobility spectrometry, and E-tongue, were used to characterize the sensory properties of HJC, with Fuding Dabai and Anji Baicha teas used as conventional and high amino acid controls, respectively. The sensory characteristics and main quality components of HJC lie somewhere between these two other teas, and somewhat closer to the conventional control. They were difficult to distinguish by color, but significant differences exist in terms of volatile organic compounds (VOCs), E-tongue values on bitterness and astringency, and their contents of major taste components. VOCs such as (E)-2-octenal, linalool, ethyl acrylate, ethyl acetate, and 2-methyl-3-furanethiol were found to be the main differential components that contributed to aroma, significantly influencing the tender chestnut aroma of HJC. Free amino acids, tea polyphenols, and ester catechins were the main differential components responsible for taste, and its harmonious phenol-to-ammonia ratio was found to affect the fresh, mellow, heavy, and brisk taste of HJC.

CircRNA 06209 inhibits cataract development by sponging miR-6848-5p and regulating ALOX15 expression.

Cataract is the leading cause of blindness in the world, and there is a lack of effective treatment drugs. CircRNA plays an important part in a variety of diseases, however, the role of circRNA in cataracts remains largely unknown. In this study, we constructed a cataract model of rats and obtained the circRNAs related to cataracts by whole transcriptome sequencing and circRNA-mRNA co-expression network. To investigate the effect and mechanism of circRNA 06209 on cataracts, we performed several in vivo and in vitro experiments, including CCK8 assay, flow cytometry, dual luciferase reporter assay, RIP assay, actinomycin D assay, and Western blot analysis. We identify that a necroptosis-related circRNA, circRNA 06209, is down-regulated in cataracts. Vitro experiments showed that up-regulation of circRNA 06209 could promote cell proliferation and inhibit cell apoptosis. Vivo experiments revealed that circRNA 06209 overexpression could inhibit the development of cataracts. Mechanistically, circRNA 06209 acts as a miRNA sponge and competitively binds to miR-6848-5p to curb the inhibitory effect of miR-6848-5p on ALOX15, thereby affecting cell viability and apoptosis. This study found that circRNA 06209 plays a critical part in inhibiting cataracts through the miR-6848-5p/ALOX15 pathway, suggesting that circRNA 06209 may be a promising therapeutic target for cataracts.

Characterization of tumor microenvironment and tumor immunology based on the double-stranded RNA-binding protein related genes in cervical cancer.

BACKGROUND: Cervical cancer is one of the most common gynecological cancers threatening women's health worldwide. Double-stranded RNA-binding proteins (dsRBPs) regulate innate immunity and are therefore believed to be involved in virus-related malignancies, however, their role in cervical cancer is not well known. METHODS: We performed RNA-seq of tumor samples from cervical cancer patients in local cohort and also assessed the RNA-seq and clinical data derived from public datasets. By using single sample Gene Set Enrichment Analysis (ssGSEA) and univariate Cox analysis, patients were stratified into distinct dsRBP clusters. Stepwise Cox and CoxBoost were performed to construct a risk model based on optimal dsRBPs clusters-related differentially expressed genes (DEGs), and GSE44001 and CGCI-HTMCP-CC were employed as two external validation cohorts. Single cell RNA sequencing data from GSE168652 and Scissor algorithm were applied to evaluated the signature-related cell population. RESULTS: The expression of dsRBP features was found to be associated with HPV infection and carcinogenesis in CESC. However, only Adenosine deaminases acting on RNA (ADAR) and Dicer, Drosha, and Argonautes (DDR) exhibited significant correlations with the overall survival (OS) of CESC patients. Based on these findings, CESC patients were divided into three dsRBP clusters. Cluster 3 showed superior OS but lower levels of ADAR and DDR. Additionally, Cluster 3 demonstrated enhanced innate immunity, with significantly higher activity in cancer immunity cycles, immune scores, and levels of tumor-infiltrating immune cells, particularly CD8+ T cells. Furthermore, a risk model based on nine dsRBP cluster-related DEGs was established. The accuracy of survival prediction for 1 to 5 years was consistently above 0.78, and this model's robust predictive capacity was confirmed by two external validation sets. The low-risk group exhibited significantly higher levels of immune checkpoints, such as PDCD1 and CTLA4, as well as a higher abundance of CD8+ T cells. Analysis of single-cell sequencing data revealed a significant association between the dsRBP signature and glycolysis. Importantly, low-risk patients showed improved OS and a higher response rate to immunotherapy, along with enduring clinical benefits from concurrent chemoradiotherapy. CONCLUSIONS: dsRBP played a crucial role in the regulation of prognosis and tumor immunology in cervical cancer, and its prognostic signature provides a strategy for risk stratification and immunotherapy evaluation.

The influence of altruistic personality, interpersonal distance and social observation on prosocial behavior: An event-related potential (ERP) study.

The psychological mechanisms that high and low altruists exhibit in different contexts remain unknown. This study examined the underlying mechanisms of the effect of altruistic personality, social observation, and interpersonal distance on prosocial behavior using event-related potentials (ERPs). Participants with high and low altruism were asked to make prosocial or non-prosocial choices toward different interpersonal distances (friends, acquaintances, or strangers) under the (non)observer condition. The electrophysiological responses to the choice stimuli were simultaneously recorded. The behavioral results demonstrated that high altruists had more prosocial choices, and these choices were unaffected by interpersonal distance and social observation. However, low altruists made more prosocial choices toward friends and acquaintances under the observer than nonobserver conditions, whereas their prosocial choices toward strangers showed no difference. The ERP results demonstrated that low altruists showed more negative N2 when the choice stimuli were toward strangers and acquaintances or under the nonobserver condition. Furthermore, low altruists showed larger P3 under the observer than nonobserver conditions when the choice stimuli were toward friends and acquaintances, while this difference was absent when the choice stimuli were toward strangers. However, for high altruists, no effect of interpersonal distance and social observation was observed in N2 and P3. These results suggest that the prosocial behavior of low altruists is mainly driven by reputational incentives, whereas high altruists are primarily motivated by concern about the well-being of others. Our findings provide insights into the prosocial behavior of high and low altruists in different contexts and support the empathy-altruism hypothesis.

Investigation on toxicity and mechanism to Daphnia magna for 14 disinfection by-products: Enzyme activity and molecular docking.

Exposure to disinfection by-products (DBPs) has been found to induce a range of toxic effects in aquatic organism. Previous studies have consistently demonstrated that a majority of DBPs have the ability to induce in vivo toxicity in aquatic organisms. However, the impact of DBPs on the metabolic processes of Daphnia magna (D. magna) and the underlying molecular toxicity mechanisms are still not well understood. Therefore, we investigated the effects of 14 DBPs on two oxidative stress enzymes and malondialdehyde (MDA) levels in D. magna. Additionally, we employed molecular docking to simulate the toxicity of DBPs to D. magna at the molecular level. This comprehensive analysis allowed us to gain further insights into the toxicity of DBPs on D. magna. The results showed that among the aliphatic DBPs, the more bromine substituents, the lower the toxicity effect, and it's opposite in the aromatic DBPs. In the detection of oxidative stress level, catalase (CAT) enzyme and superoxide dismutase (SOD) enzyme in D. magna under compound stress showed a low increase and decrease with the increase of concentration. The level of MDA showed a positive correlation with the concentration. In the last, molecular docking simulations have shown promise in predicting the toxicity of DBPs and providing insights into their toxic effects to a certain extent, and the docking situation of P53 is slightly different. Hence, it is imperative to further regulate the presence of aromatic DBPs due to their pronounced toxic effects on D. magna, and these simulations can be complemented with actual experiments to enhance our understanding of the toxicity mechanisms of DBPs.

Genomic profile of Chinese patients with endometrial carcinoma.

BACKGROUNDS: Endometrial carcinoma (EC) is one of the most commonly diagnosed gynecologic malignancy in China. However, the genetic profile of Chinese EC patients has not been well established yet. METHODS: In current study, 158 Chinese EC patients were subjected to next-generation sequencing assay (74 took testing of EC-related 20-genes panel, and 84 took the expanded panel). Of the 158 patients, 91 patients were performed germline mutation testing using the expanded panel. Moreover, the public datasets from TCGA and MSKCC were utilized to compare the genomic differences between Chinese and Western EC patients. The proteomic and transcriptomic from CPTAC and TCGA were derived and performed unsupervised clustering to identify molecular subtypes. RESULTS: Among the 158 patients analyzed, a significant majority (85.4%) exihibited at least one somatic alteration, with the most prevalent alterations occurring in PTEN, PIK3CA, TP53, and ARID1A. These genomic alterations were mainly enriched in the PI3K, cell cycle, RAS/RAF/MAPK, Epigenetic modifiers/Chromatin remodelers, and DNA damage repair (DDR) signaling pathways. Additionally, we identified ten individuals (11.0%) with pathogenic or likely pathogenic germline alterations in seven genes, with the DDR pathway being predominantly involved. Compared to Western EC patients, Chinese EC patients displayed different prevalence in AKT1, MET, PMS2, PIK3R1, and CTCF. Notably, 69.6% of Chinese EC patients were identified with actionable alterations. In addition, we discovered novel molecular subtypes in ARID1A wild-type patients, characterized by an inferior prognosis, higher TP53 but fewer PTEN and PIK3CA alterations. Additionally, this subtype exhibited a significantly higher abundance of macrophages and activated dendritic cells. CONCLUSION: Our study has contributed valuable insights into the unique germline and somatic genomic profiles of Chinese EC patients, enhancing our understanding of their biological characteristics and potential therapeutic avenues. Furthermore, we have highlighted the presence of molecular heterogeneity in ARID1A-wild type EC patients, shedding light on the complexity of this subgroup.