scATAC-Ref: a reference of scATAC-seq with known cell labels in multiple species.

Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.

SpatialRef: a reference of spatial omics with known spot annotation.

Spatial omics technologies have enabled the creation of intricate spatial maps that capture molecular features and tissue morphology, providing valuable insights into the spatial associations and functional organization of tissues. Accurate annotation of spot or domain types is essential for downstream spatial omics analyses, but this remains challenging. Therefore, this study aimed to develop a manually curated spatial omics database (SpatialRef, https://bio.liclab.net/spatialref/), to provide comprehensive and high-quality spatial omics data with known spot labels across multiple species. The current version of SpatialRef aggregates >9 million manually annotated spots across 17 Human, Mouse and Drosophila tissue types through extensive review and strict quality control, covering multiple spatial sequencing technologies and >400 spot/domain types from original studies. Furthermore, SpatialRef supports various spatial omics analyses about known spot types, including differentially expressed genes, spatially variable genes, Gene Ontology (GO)/KEGG annotation, spatial communication and spatial trajectories. With a user-friendly interface, SpatialRef facilitates querying, browsing and visualizing, thereby aiding in elucidating the functional relevance of spatial domains within the tissue and uncovering potential biological effects.

scImmOmics: a manually curated resource of single-cell multi-omics immune data.

Single-cell sequencing technology has enabled the discovery and characterization of subpopulations of immune cells with unique functions, which is critical for revealing immune responses under healthy or disease conditions. Efforts have been made to collect and curate single-cell RNA sequencing (scRNA-seq) data, yet an immune-specific single-cell multi-omics atlas with harmonized metadata is still lacking. Here, we present scImmOmics (https://bio.liclab.net/scImmOmics/home), a manually curated single-cell multi-omics immune database constructed based on high-quality immune cells with known immune cell labels. Currently, scImmOmics documents >2.9 million cell-type labeled immune cells derived from seven single-cell sequencing technologies, involving 131 immune cell types, 47 tissues and 4 species. To ensure data consistency, we standardized the nomenclature of immune cell types and presented them in a hierarchical tree structure to clearly describe the lineage relationships within the immune system. scImmOmics also provides comprehensive immune regulatory information, including T-cell/B-cell receptor sequencing clonotype information, cell-specific regulatory information (e.g. gene/chromatin accessibility/protein/transcription factor states within known cell types, cell-to-cell communication and co-expression networks) and immune cell responses to cytokines. Collectively, scImmOmics is a comprehensive and valuable platform for unraveling the heterogeneity and diversity of immune cells and elucidating the specific regulatory mechanisms at the single-cell level.

SEanalysis 2.0: a comprehensive super-enhancer regulatory network analysis tool for human and mouse.

Super-enhancers (SEs) play an essential regulatory role in various biological processes and diseases through their specific interaction with transcription factors (TFs). Here, we present the release of SEanalysis 2.0 (http://licpathway.net/SEanalysis), an updated version of the SEanalysis web server for the comprehensive analyses of transcriptional regulatory networks formed by SEs, pathways, TFs, and genes. The current version added mouse SEs and further expanded the scale of human SEs, documenting 1 167 518 human SEs from 1739 samples and 550 226 mouse SEs from 931 samples. The SE-related samples in SEanalysis 2.0 were more than five times that in version 1.0, which significantly improved the ability of original SE-related network analyses ('pathway downstream analysis', 'upstream regulatory analysis' and 'genomic region annotation') for understanding context-specific gene regulation. Furthermore, we designed two novel analysis models, 'TF regulatory analysis' and 'Sample comparative analysis' for supporting more comprehensive analyses of SE regulatory networks driven by TFs. Further, the risk SNPs were annotated to the SE regions to provide potential SE-related disease/trait information. Hence, we believe that SEanalysis 2.0 has significantly expanded the data and analytical capabilities of SEs, which helps researchers in an in-depth understanding of the regulatory mechanisms of SEs.

A MRI radiomics-based model for prediction of pelvic lymph node metastasis in cervical cancer.

BACKGROUND: Cervical cancer (CC) is a common malignancy of the female reproductive tract, and preoperative prediction of lymph node metastasis (LNM) is essential. This study aims to design and validate a magnetic resonance imaging (MRI) radiomics-based predictive model capable of detecting LNM in patients diagnosed with CC. METHODS: This retrospective analysis incorporated 86 and 38 CC patients into the training and testing groups, respectively. Radiomics features were extracted from MRI T2WI, T2WI-SPAIR, and axial apparent diffusion coefficient (ADC) sequences. Selected features identified in the training group were then used to construct a radiomics scoring model, with relevant LNM-related risk factors having been identified through univariate and multivariate logistic regression analyses. The resultant predictive model was then validated in the testing cohort. RESULTS: In total, 16 features were selected for the construction of a radiomics scoring model. LNM-related risk factors included worse differentiation (P < 0.001), more advanced International Federation of Gynecology and Obstetrics (FIGO) stages (P = 0.03), and a higher radiomics score from the combined MRI sequences (P = 0.01). The equation for the predictive model was as follows: -0.0493-2.1410 × differentiation level + 7.7203 × radiomics score of combined sequences + 1.6752 × FIGO stage. The respective area under the curve (AUC) values for the T2WI radiomics score, T2WI-SPAIR radiomics score, ADC radiomics score, combined sequence radiomics score, and predictive model were 0.656, 0.664, 0.658, 0.835, and 0.923 in the training cohort, while these corresponding AUC values were 0.643, 0.525, 0.513, 0.826, and 0.82 in the testing cohort. CONCLUSIONS: This MRI radiomics-based model exhibited favorable accuracy when used to predict LNM in patients with CC. Relative to the use of any individual MRI sequence-based radiomics score, this predictive model yielded superior diagnostic accuracy.

Impact of COVID-19 pandemic on specialty training in obstetrics and gynaecology in Hong Kong: is there a concern about the future prospect?

INTRODUCTION: The COVID-19 pandemic in the past few years led to major adjustments in the provision of healthcare. This study aimed to investigate trainees' perception of impact of the pandemic on specialty training in Obstetrics & Gynaecology (O&G) in Hong Kong. METHODS: A cross-sectional questionnaire survey was performed on all the O&G trainees and the young fellows of the Hong Kong College of Obstetricians and Gynaecologists (HKCOG). The questionnaires included 5 parts: demographic data, impact on clinical activities, redeployment, educational activities and career progression. RESULTS: A total of 104 questionnaires (92.9%) were received for final analysis. The majority of the participants had reductions in elective and emergency operations, as well as exposure to in-patient admissions and out-patient clinics in both obstetrics and gynaecology. The reduction was most significant in elective gynaecology operations. One-third (34.6%) of the participants had been redeployed to other departments, and educational activities were reduced during the pandemic. Around 58% of the trainees were concerned with the reduction in clinical exposure, and 78% worried they would not be able to log sufficient number of surgical procedures. Basic trainees were significantly more worried than higher trainees. Around half of the trainees had doubts or regrets about choosing to undergo O&G specialty training. CONCLUSION: The O&G trainees in Hong Kong perceived that the COVID-19 pandemic had significant negative impacts on their training. Many trainees were worried they would not be able to attain the required level of competence when they complete their specialist training.

[Platelet-to-lymphocyte ratio as a biomarker for predicting coronary artery lesions in Chinese children with Kawasaki disease: a Meta analysis]. / è¡€å°æ¿ä¸Žæ·‹å·´ç»†èƒžæ¯”å€¼å¯¹ä¸­å›½å·å´Žç— æ‚£å„¿å† çŠ¶åŠ¨è„‰ç— å˜é¢„æµ‹ä»·å€¼çš„Meta分析.

OBJECTIVES: To systematically evaluate the value of the platelet-to-lymphocyte ratio (PLR) in predicting coronary artery lesions (CAL) in Chinese children with Kawasaki Disease (KD). METHODS: A comprehensive search was conducted in databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, China Biomedical Literature Database, and China Science and Technology Journal Database from inception to December 2022. The quality of the included literature was assessed using the Newcastle-Ottawa Scale, and a Meta analysis was performed using Stata 15.1. RESULTS: A total of ten published reports, involving 3 664 Chinese children with KD, were included in this Meta analysis, of whom 1 328 developed CAL. The Meta analysis revealed a sensitivity of 0.78 (95%CI: 0.71-0.83), specificity of 0.71 (95%CI: 0.61-0.80), overall diagnostic odds ratio of 8.69 (95%CI: 5.02-15.06), and an area under the curve of the summary receiver operating characteristic of 0.82 (95%CI: 0.78-0.85) for PLR in predicting CAL in the children with KD. The sensitivity, specificity, and area under the curve of summary receiver operating characteristic were lower for PLR alone compared to PLR in combination with other indicators. Sensitivity analysis demonstrated the stability of the Meta analysis results with no significant changes upon excluding individual studies. However, a significant publication bias was observed (P<0.001). CONCLUSIONS: PLR demonstrates certain predictive value for CAL in Chinese children with KD.

Syntheses of Bufospirostenin A and Ophiopogonol A by a Conformation-Controlled Transannular Prins Cyclization.

Controlling the conformation of medium-sized rings is challenging because of their flexibility and ring strain effects. Herein, we report non-Curtin-Hammett conditions for the precise control of the conformation of cyclodecenones to effect the first cis-selective transannular Prins cyclization, which enabled concise syntheses of the 5(10→1)abeo-steroids bufospirostenin A and ophiopogonol A in only seven steps from inexpensive starting materials. Computational results indicated that the key cyclization was kinetically controlled and proceeded via either a Prins pathway or a carbonyl-ene pathway, depending on the reaction conditions. Moreover, conformational isomerization played a critical role in determining the stereochemistry of the products.

The impact of deep learning reconstruction on image quality and coronary CT angiography-derived fractional flow reserve values.

OBJECTIVES: To explore the impact of deep learning reconstruction (DLR) on image quality and machine learning-based coronary CT angiography (CTA)-derived fractional flow reserve (CT-FFRML) values. METHODS: Thirty-three consecutive patients with known or suspected coronary artery disease who underwent coronary CTA and subsequent invasive coronary angiography were enrolled. DLR was compared with filtered back projection (FBP), statistical-based iterative reconstruction (SBIR), model-based iterative reconstruction (MBIR) Cardiac, and MBIR Cardiac sharp for objective image qualities of coronary CTA. Invasive fractional flow reserve (FFR) and quantitative flow ratio (QFR) were used as the reference standards. The diagnostic performances of different reconstruction approach-based CT-FFRML were calculated. RESULTS: A total of 182 lesions in 33 patients were enrolled for analysis. The image quality of DLR was superior to the others. There were no significant differences in the CT-FFRML values among these five approaches (all p > 0.05). Of the 182 lesions, 17 had invasive FFR results, and 70 had QFR results. Using FFR as a reference, MBIR Cardiac, MBIR Cardiac sharp, and DLR achieved equal diagnostic performance, slightly higher than the other reconstruction approaches (MBIR Cardiac, MBIR Cardiac sharp, and DLR: AUC = 0.82, FBP and AIDR: AUC = 0.78, all p > 0.05). Using QFR as a reference, the AUCs of FBP, SBIR, MBIR Cardiac, MBIR Cardiac sharp, and DLR were 0.83, 0.81, 0.86, 0.84, and 0.83, respectively (all p > 0.05). CONCLUSIONS: Our study showed that the DLR algorithm improved image quality, but there were no significant differences in the CT-FFRML values and diagnostic performance among different reconstruction approaches. KEY POINTS: • Deep learning-based image reconstruction (DLR) improves the image quality of coronary CTA. • CT-FFRML values and diagnostic performance of DLR revealed no significant differences compared to other reconstruction approaches.

Longitudinal association between poor parental supervision and risk-taking behavior: The role of self-control and school climate.

INTRODUCTION: Although poor parental supervision has been associated with an increased adolescents' propensity for risk-taking behavior, few researchers have investigated nuanced mechanisms of how and for whom from the perspective of "family × school." Inspired by ecological system theory and self-control theory, this study aimed to investigate the mediating role of self-control and the moderating role of school climate between the link between poor parental supervision and risk-taking behavior. METHODS: Four hundred and ninety-one Chinese adolescents (231 females, Mage = 15.39 ± 1.36) were recruited to participate in a three-wave longitudinal study (3 months apart) and complete questionnaires regarding poor parental supervision (W1), school climate (W1), self-control (W2), and risk-taking behavior (W1/W3). RESULTS: After controlling for W1 risk-taking behavior, our moderated mediation model indicated that W1 poor parental supervision was positively related to W3 risk-taking behavior by restraining the development of W2 self-control. Additionally, a high level of school climate as a protective factor buffered the negative impact of poor parental supervision on adolescents' self-control, further reducing risk-taking behavior. CONCLUSION: Our findings shed light on the processing mechanisms between poor parental supervision and risk-taking behavior among Chinese adolescents and underscore the importance of effective preventions and interventions to facilitate adolescents' healthy development.

Prenatal Diagnosis and Pregnancy Outcomes of Fetuses With Orofacial Cleft: A Retrospective Cohort Study in Two Centres in Hong Kong.

OBJECTIVE: To evaluate the local incidence of orofacial cleft (OFC) encountered in fetal morphology scan and prenatal diagnosis, genetic etiology of fetuses with or without other structural abnormalities, and their pregnancy outcomes. DESIGN: Retrospective cohort study. SETTING: Two maternal fetal medicine units, tertiary hospitals, Hong Kong. PARTICIPANTS: All pregnant women with antenatal diagnosis of fetal OFC between January 2016 and December 2020 (N = 66). RESULTS: OFC has an incidence of 0.13% among pregnancies in Hong Kong and 28.8% (19/66) were syndromic cleft that exhibited other fetal structural anomalies. There were 55 cases (84.6%) who opted for invasive prenatal diagnostic testing. Genetic defects were identified in 25.8% (17/66) of this cohort, including 14 pathogenic variants. The detection rate in the syndromic cases is 68.4% (13/19) which was significantly higher than 8.5% (4/47) among non-syndromic cases. Aneuploidies would be the most common cause, accounting for 9.1% (6/66). Chromosomal microarray analysis (CMA) provided an incremental diagnostic yield of 6.1% compared to conventional karyotyping. A total of 29 live births including 3 cases of a variant of uncertain significance and 26 cases without genetic abnormalities detected have continued pregnancy to birth. There were 87.5% (21/24) without detectable pathogenic genetic abnormality reported good long-term outcomes. The chance of OFC fetuses having a good long-term outcome was significantly higher if no genomic variant was detected (P < .001). CONCLUSIONS: Invasive prenatal tests with CMA should be offered to pregnancies with OFC regardless of the type. It has provided incremental diagnostic yield over conventional karyotyping and helped in prenatal and genetic counseling. A negative result in non-syndromic OFC favors couples to keep the pregnancy.

SEanalysis: a web tool for super-enhancer associated regulatory analysis.

Super-enhancers (SEs) have prominent roles in biological and pathological processes through their unique transcriptional regulatory capability. To date, several SE databases have been developed by us and others. However, these existing databases do not provide downstream or upstream regulatory analyses of SEs. Pathways, transcription factors (TFs), SEs, and SE-associated genes form complex regulatory networks. Therefore, we designed a novel web server, SEanalysis, which provides comprehensive SE-associated regulatory network analyses. SEanalysis characterizes SE-associated genes, TFs binding to target SEs, and their upstream pathways. The current version of SEanalysis contains more than 330 000 SEs from more than 540 types of cells/tissues, 5042 TF ChIP-seq data generated from these cells/tissues, DNA-binding sequence motifs for ∼700 human TFs and 2880 pathways from 10 databases. SEanalysis supports searching by either SEs, samples, TFs, pathways or genes. The complex regulatory networks formed by these factors can be interactively visualized. In addition, we developed a customizable genome browser containing >6000 customizable tracks for visualization. The server is freely available at http://licpathway.net/SEanalysis.

Design, Synthesis, and Evaluation of Monoamine Oxidase A Inhibitors⁻Indocyanine Dyes Conjugates as Targeted Antitumor Agents.

Monoamine oxidase A (MAOA) is an important mitochondria-bound enzyme that catalyzes the oxidative deamination of monoamine neurotransmitters. Accumulating evidence suggests a significant association of increased MAOA expression and advanced high-grade prostate cancer (PCa) progression and metastasis. Herein, a series of novel conjugates combining the MAOA inhibitor isoniazid (INH) and tumor-targeting near-infrared (NIR) heptamethine cyanine dyes were designed and synthesized. The synthesized compounds G1⁻G13 were evaluated in vitro for their cytotoxicity against PC-3 cells using the MTT assay, and molecular docking studies were performed. Results showed that most tested compounds exhibited improved antitumor efficacy compared with INH. Moreover, conjugates G10 and G11 showed potent anticancer activity with IC50 values (0.85 and 0.4 µM respectively) comparable to that of doxorubicin (DOX). This may be attributable to the preferential accumulation of these conjugates in tumor cells. G10, G11, and G12 also demonstrated moderate MAOA inhibitory activities. This result and the results of molecular docking studies were consistent with their cytotoxicity activities. Taken together, these data suggest that a combination of the MAOA inhibitor INH with tumor-targeting heptamethine cyanine dyes may prove to be a highly promising tool for the treatment of advanced prostate cancer.

Core/Shell Structured Fe3O4@TiO2-DNM Nanospheres as Multifunctional Anticancer Platform: Chemotherapy and Photodynamic Therapy Research.

The dose-dependent toxicity and low specificity against cancerous cells have restricted the clinical use of daunomycin (DNM). Titanium dioxide (TiO2) has been wildly used as an inorganic photodynamic therapy (PDT) agent and drug carrier. To facilitate the targeted drug delivery and combined therapy, in the present study, TiO2-coated Fe3O4 nanoparticles (Fe3O4@TiO2 NPs) were employed to load DNM and the drug-loaded Fe3O4@TiO2-DNM Nps exhibited smart pH-controlled releasing and satisfactory cytotoxicity as well as photocytotocity. The combination of prussian blue staining and fluorescence methods evidenced the effortless cell internalization of the fabricated Fe3O4@TiO2-DNM Nps for the cancer cells. The cell cycle status experiments indicated that the as-prepared nanospheres arrested the S and G2/M periods of the cancer cell proliferation in the dark, and further induced the apoptosis under the irradiation of ultraviolet light. The cell apoptotic results revealed that the apoptosis induced by the Fe3O4@TiO2-DNM Nps was in the early stage. The constructed Fe3O4@TiO2-DNM NPs have been endowed with multifunctions that allow them to selectively deliver combinatorial therapeutic payload and exhibit integrated therapeutic effectiveness to tumors.

Mesenteric cystic lymphatic malformation: a rare case report and review of the literature.

Background: Mesenteric cystic lymphatic malformation (LM) is a rare congenital benign malformation in adults, and its location in the mesentery of the sigmoid colon is even rarer. Case Description: We describe a rare case of LM of the mesentery in a 49-year-old woman. The patient was inadvertently identified during a physical examination 1 month earlier. Transvaginal ultrasound and magnetic resonance imaging (MRI) revealed the presence of an intrapelvic mass posterior to the uterus and right anterior to the sigmoid colon. According to the results of the ultrasound, the mass showed hypoechoic solid features with a blood flow signal, and MRI showed that the internal enhancement of the mass was uneven. According to its imaging characteristics, it was preliminarily speculated as a stromal tumor. The patient underwent laparoscopic fenestration and drainage of a sigmoid mesocolic cyst. The patient underwent laparoscopic fenestration and drainage of the sigmoid mesocolic cyst. The pathological diagnosis was cystic lymphangioma of the sigmoid mesangium. After the operation, the patient recovered well without any complications. No recurrence was observed during the 3-month follow-up. Conclusions: LM is a challenging and rare disease, and its diagnosis is difficult. However, the combination of imaging examination and endoscopic ultrasound (EUS) technology can significantly improve the accurate diagnosis rate of the disease. Complete resection is the best choice for definite diagnosis and prevention of recurrence. It has been proved that laparoscopic surgery is a safe and feasible method for the treatment of this disease.

Adenomatoid tumor of the uterus: analysis of misdiagnosed cases and a literature review.

Adenomatoid tumors are rare, specific, benign tumors of the reproductive tract that originate from mesenchymal tissue. A patient was diagnosed with uterine fibroids 1 year previously when a mass of approximately 30 mm was found in the left adnexal region during a physical examination. At 1 year of follow-up, ultrasound showed that the mass in the left adnexal area had greatly increased to 61 × 45 × 50 mm. Contrast-enhanced pelvic magnetic resonance imaging (MRI) was performed before surgery and suggested a borderline tumor. Histopathology suggested signet ring cell carcinoma, and an immunohistochemical examination suggested a uterine adenomatoid tumor. Our suspicion of a borderline tumor was based mainly on the following features: the mass had increased in size within 1 year, the cancer antigen 125 concentration had increased, and several lymph nodes in the pelvic and groin regions showed positive signals on MRI enhancement. Uterine adenomatoid tumors are challenging to diagnose, especially adenomatosis with signet ring cells. However, the accuracy of diagnosing this disease can be greatly improved by combining ultrasound and MRI. This article describes the most comprehensive and reliable imaging features of ultrasound and MRI, which play an important role in diagnosing uterine adenomatoid tumors and provide useful information for clinicians.

Palladium-Catalyzed Dearomative Heck/Suzuki Coupling of C2-Deuterated or C2-Nonsubstituted Indoles.

A palladium-catalyzed dearomative diarylation of C2-deuterated or C2-nonsubstituted indoles through domino Heck/Suzuki coupling is established. Relying on electron-deficient phosphite ligand, side reactions including intermolecular Suzuki coupling and intramolecular C-D/H arylation are inhibited and a wide range of 2,3-diarylated indolines bearing vicinal tertiary stereocenters including deuterated ones are afforded in moderate to excellent yields (up to 94%) and excellent diastereoselectivities (>20:1). The catalyst loading can be lowered to 0.02 mol % at elevated temperature.

Advances in precision therapy of low-grade serous ovarian cancer: A review.

Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of ovarian cancer that accounts for approximately 6% to 10% of serous ovarian cancers. The clinical treatment of LGSOC is similar to that of high-grade serous ovarian carcinoma, however, its clinical and molecular characteristics are different from those of high-grade serous ovarian carcinoma. This article reviews the research on gene diagnosis, surgical treatment, chemotherapy, and biological therapy of LGSOC, providing reference for clinical diagnosis and treatment of LGSOC. Surgery is the cornerstone of LGSOC treatment and maximum effort must be made to achieve R0 removal. Although LGSOC is not sensitive to chemotherapy, postoperative platinum-based combination chemotherapy remains the first-line treatment option for LGSOC. Additional clinical trials are needed to confirm the clinical benefits of chemotherapy and explore new chemotherapy protocols. Hormone and targeted therapies may also play important roles. Some patients, particularly those with residual lesions after treatment, may benefit from hormone maintenance therapy after chemotherapy. Targeted therapies, such as MEKi, show good application prospects and are expected to change the treatment pattern of LGSOC. Continuing to further study the genomics of LGSOC, identify its specific gene changes, and combine traditional treatment methods with precision targeted therapy based on second-generation sequencing may be the direction for LGSOC to overcome the treatment bottleneck. In future clinical work, comprehensive genetic testing should be carried out for LGSOC patients to accumulate data for future scientific research, in order to find more effective methods and drugs for the treatment of LGSOC.

Resveratrol activates MAPK/ERK pathway to regulate oestrogen metabolism in type I endometrial cancer.

OBJECTIVE: Endometrial cancer (EC) is an oestrogen-dependent tumour, the occurrence of which is closely related to an imbalance of oestrogen homeostasis. Our previous studies explored the effects of Resveratrol(Res) on oestrogen metabolism. However, systematic research on the exact mechanism of action of Res is still lacking. Based on network pharmacology, molecular docking and animal experiments, the effects and molecular mechanisms of Res on endometrial cancer were investigated. METHODS: The target of Res was obtained from the high-throughput experiment and reference-guided database of TCM (HERB) and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases, and the target of endometrial cancer was obtained by using the Genecards database. Venny map was used to obtain the intersection target of Res in the treatment of endometrial cancer, and the protein interaction network of the intersection target was constructed by importing the data into the STRING database. Then, the drug-disease-target interaction network was constructed based on Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for intersection targets using the OmicShare cloud platform. Res and core targets were analysed by molecular docking. EC model mice induced by MNNG were randomly divided into the control group, Res group, MNNG group, MNNG + Res group, and MNNG + Res + MAPK/ERKi group. The protein levels of ERK and p-ERK in the mouse uterus were detected by Western blot. The levels of E1, E2, E3, 16-epiE3, 17-epiE3, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 3-MeOE1, 2-OHE1, 4-OHE1, 2-OHE2, 4-OHE2, and 16α-OHE1 in the serum and endometrial tissue of mice were measured by LC‒MS/MS. RESULTS: A total of 174 intersection targets of Res anti-endometrial cancer were obtained. The signalling pathways analysed by KEGG enrichment included the AGE-RAGE signalling pathway in diabetic complications, the PI3K-Akt signalling pathway and the MAPK signalling pathway. The top 10 core targets were MAPK3, JUN, TP53, CASP3, TNF, IL1B, AKT1, FOS, VEGFA and INS. Molecular docking showed that in addition to TNF, other targets had good affinity for Res, and the binding activity with MAPK3 was stable. Western blot results showed that Res increased the phosphorylation level of ERK and that MAPK/ERKi decreased ERK activation. In the LC-MS/MS analysis, the levels of 2-MeOE1, 2-MeOE2 and 4-MeOE1 in serum and uterine tissue showed a significantly decreasing trend in the MNNG group, while that of 4-OHE2 was increased (P < 0.05). The concentrations of 4-MeOE1 in serum and 2-MeOE1 and 2-MeOE2 in the endometrial tissue of mice were significantly increased after Res treatment, and those of 4-OHE2 in the serum and uterus of mice were significantly decreased (P < 0.05). Meanwhile, in the MAPK/ERKi intervention group, the effect of Res on the reversal of oestrogen homeostasis imbalance was obviously weakened. CONCLUSION: Res has multiple targets and multiple approaches in the treatment of endometrial cancer. In this study, it was found that Res regulates oestrogen metabolism by activating the MAPK/ERK pathway. This finding provides a new perspective for subsequent research on the treatment of endometrial cancer.

scBlood: A comprehensive single-cell accessible chromatin database of blood cells.

The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from ∼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.