Postmenopausal endometrial non-benign lesion risk classification through a clinical parameter-based machine learning model.

OBJECTIVE: This study aimed to develop and evaluate a machine learning model utilizing non-invasive clinical parameters for the classification of endometrial non-benign lesions, specifically atypical hyperplasia (AH) and endometrioid carcinoma (EC), in postmenopausal women. METHODS: Our study collected clinical parameters from a cohort of 999 patients with postmenopausal endometrial lesions and conducted preprocessing to identify 57 relevant characteristics from these irregular clinical data. To predict the presence of postmenopausal endometrial non-benign lesions, including atypical hyperplasia and endometrial cancer, we employed various models such as eXtreme Gradient Boosting (XGBoost), Random Forest (RF), Logistic Regression (LR), Support Vector Machine (SVM), Back Propagation Neural Network (BPNN), as well as two ensemble models. Additionally, a test set was performed on an independent dataset consisting of 152 patients. The performance evaluation of all models was based on metrics including the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, precision, and F1 score. RESULTS: The RF model demonstrated superior recognition capabilities for patients with non-benign lesions compared to other models. In the test set, it attained a sensitivity of 88.1% and an AUC of 0.93, surpassing all alternative models evaluated in this study. Furthermore, we have integrated this model into our hospital's Clinical Decision Support System (CDSS) and implemented it within the outpatient electronic medical record system to continuously validate and optimize its performance. CONCLUSIONS: We have trained a model and deployed a system with high discriminatory power that may provide a novel approach to identify patients at higher risk of postmenopausal endometrial non-benign lesions who may benefit from more tailored screening and clinical intervention.

Macrophage KLF15 prevents foam cell formation and atherosclerosis via transcriptional suppression of OLR-1.

BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.

Supernatural: Artificial Nucleobases and Backbones to Program Hybridization-Based Assemblies and Circuits.

The specificity and predictability of hybridization make oligonucleotides a powerful platform to program assemblies and networks with logic-gated responses, an area of research which has grown into a field of its own. While the field has capitalized on the commercial availability of DNA oligomers with its four canonical nucleobases, there are opportunities to extend the capabilities of the hardware with unnatural nucleobases and other backbones. This Topical Review highlights nucleobases that favor hybridizations that are empowering for assemblies and networks as well as two chiral XNAs than enable orthogonal hybridization networks.

Sophisticated yet Convenient Information Encryption/Decryption Based on Synergistically Time-/Temperature-Resolved Photonic Inks.

Exploring high-safety but convenient encryption and decryption technologies to combat threats of information leakage is urgently needed but remains a great challenge. Here, a synergistically time- and temperature-resolved information coding/decoding solution based on functional photonic inks is demonstrated. Encrypted messages can be stored into multiple channels with dynamic-color patterns, and information decryption is only enabled at appointed temperature and time points. Notably, the ink can be easily processed into quick-response codes and multipixel plates. With high transparency and responsive color variations controlled by ink compositions and ambient temperatures, advanced 3D stacking multichannel coding and Morse coding techniques can be applied for multi-information storage, complex anticounterfeiting, and information interference. This study paves an avenue for the design and development of dynamic photonic inks and complex encryption technologies for high-end anticounterfeiting applications.

An aggregation-induced emission fluorogen/DNA probe carrying an endosome escaping pass for tracking reduced thiol compounds in cells.

The fluorescent nanoprobes for reduced thiol compounds (represented by glutathione, GSH) are constructed based on the aggregation-induced emission (AIE) luminescence mechanism and endosome escape technology. First, a DNA sequence was designed with the decoration of biotin at the 5'-end, disulfide bound in the internal portion, and amino at the 3'-end. The aptamer of the MCF-7 cell was also one of the most important structures in our DNA sequence for the selectivity of MCF-7 cells. We modified streptavidin-modified magnetic beads (MB) with biotin-modified influenza virus hemagglutinin peptide (HA) and biotin-DNA-amino to form MB/DNA/HA. Carboxyl-modified tetraphenylethylene (TPE), an iconic AIE fluorogen, was bonded with amino-modified DNA by covalent interactions (TPE/DNA). Then, the TPE molecule was attached on the outer layer of MB via biotin-modified TPE/DNA to form MB/DNA/HA/TPE. Compared with traditional AIE/biomolecule conjugates, the nanoprobe had an enhanced endosome escape function, due to the assembly of HA. This construction made the intracellular fluorescence response more accurate. In the presence of reduced thiol compounds (take GSH, for example), the disulfide bond on the DNA was reduced by thiol-disulfide exchange reactions and the TPE molecule was released into the solution. The shedding TPE molecule was more hydrophobic than TPE/DNA and the conversion of TPE/DNA to shedding TPE could lead to the aggregation of the TPE fluorogen. Thus, its fluorescence was enhanced. Under the optimized condition, the fluorescence intensity increased with the increase in concentration of GSH' ranging from 1.0 × 10-9 M to 1.0 × 10-5 M' and the detection limit was 1.0 × 10-9 M. The relative standard deviation (RSD) was calculated to be 3.6%. The recovery in cell homogenate was from 94.5 to 102.7%. The nanoprobe provided a way for the detection of reduced thiol compounds in MCF-7 cells. We envision that, in the near future, our strategy of DNA-instructed AIE could be widely applied for biosensing and bioimaging in vitro and even in vivo with dramatically enhanced sensitivity. Graphical Abstract.

Fertility Outcomes After Laparoscopic Cystectomy in Infertile Patients with Stage III-IV Endometriosis: a Cohort with 6-10 years of Follow-up.

INTRODUCTION: Ovarian endometriosis is the most common type of endometriosis (EM), affecting more than 40% of women with EM. Currently, surgical intervention is still controversial in infertile patients with ovarian endometriosis, especially in those with stage III-IV EM. Very few studies have been done to analyze long-term pregnancy results in patients with endometrioma more than 5 years after surgery. Therefore, the aim of this study was to explore the pregnancy outcomes and the related factors in patients with endometrioma and stage III-IV endometriosis during a long-term follow-up postoperatively. METHODS: We collected 347 patients with ovarian endometriosis, which included 59 infertile patients with stage III-IV endometriosis who had a minimum of 5 years of postoperative follow-up after undergoing laparoscopic excision of ovarian endometriomas performed by a single doctor at the Peking Union Medical College Hospital from January 2009 to April 2013. RESULTS: A total of 59 infertile patients were recruited. The mean age was 31.8 ± 3.6 years. The mean size of the endometriomas was 6.8 ± 3.3 cm. Before surgery, dysmenorrhea was present in 88.1% (52/59) of the cases, while chronic pelvic pain was reported in nine cases (15.3%). A total of 20.3% (12/59) of cases were concurrent with leiomyoma, 52.5% (31/59) with deep infiltrating endometriosis (DIE), and 39.0% (23/59) with adenomyosis. During laparoscopy, 21 cases were diagnosed as stage III (35.6%) and 38 as stage IV (64.4%) EM according to the revised American Fertility Society (AFS) classification. After laparoscopic cystectomy, 38 (64.4%) patients became successfully pregnant by the 5th year. All the patients were divided into two groups according to the postoperative pregnancy outcomes. In univariate analysis, the higher mean age and concurrent diagnosis of adenomyosis were seen to be related to poor postoperative pregnancy outcomes (p < 0.05). In multivariate analysis, however, the mean age, chronic pelvic pain (CPP), and adenomyosis were independent risk factors of pregnancy outcomes between the two groups (p < 0.05). With a minimum follow-up of 6 years, 23.7% (14/59) of recurrence was observed in the entire study cohort. CONCLUSION: Infertile patients with endometrioma and stage III-IV EM may have lower pregnancy rates after laparoscopic cystectomy if they are older and present with CPP and adenomyosis. Our data showed a lower rate of recurrence but a higher rate of pregnancy after surgery.

Activated Plasmonic Nanoaggregates for Dark-Field in Situ Imaging for HER2 Protein Imaging on Cell Surfaces.

Dark-field microscopy (DFM) based on localized surface plasmon resonance (LSPR) was used for observation of experimental phenomena, which is a hopeful nondamaging and non-photobleaching biological imaging technique. In this strategy, plasma nanoaggregates with stronger scattering efficiency were formed in the presence of the target, causing a "turn-on" phenomenon, when asymmetry modified AuNPs were introduced as probes with zero LSPR background. First, Au1-N3 probe and Au2-C≡C probe were designed for the cycloaddition between azide and alkyne to form AuNP dimers under catalytic action by Cu+, which was obtained from the reduction of Cu2+ by sodium ascorbate. The two kinds of probes were successfully used for the detection of Cu2+ in rat serum. Then, to apply this concept to protein on cells, DNA and antibody were modified on the probes. DNA1/Au1-N3 probe and anti-HER2/Au2-C≡C probe were proposed for HER2 protein DFM on cells. By designing an aptamer sequence in primer, the rolling circle amplification (RCA) was introduced in HER2 DFM on cells, and the image signal was much brighter than that from no-RCA. The unique design made it easier to discriminate the target signal from background noise in cell DFM. This method might be used in the fields of molecular diagnostics and cell imaging.

Exploration of a KI-catalyzed oxidation system for direct construction of bispyrrolidino[2,3-b]indolines and the total synthesis of (+)-WIN 64821.

A facile and environmentally benign KI(cat.)/NaBO3·4H2O oxidation system has been developed for the tandem oxidative aminocyclization/coupling of tryptamines, affording a series of 3a,3a'-bispyrrolidino[2,3-b]indolines with high efficiency (up to 94% yield). This reaction features an electrophilic "I+" mechanism, which is importantly quite different from and milder than the typical radical-involving process, and can be readily amplified for the total synthesis of (+)-WIN 64821.

Risk factors for postoperative recurrence of ovarian endometriosis: long-term follow-up of 358 women.

OBJECTIVE: To explore the risk factors for the recurrence of endometrioma and the risk factors for the recurrence of endometriosis-related pain after long-term follow-up. METHODS: This study retrospectively analyzed 358 women with endometriomas who had a minimum of 5-years follow up after laparoscopic endometrioma excision, which was performed at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into recurrence group and nonrecurrence group. Analysis was performed with regard to preoperative history, laboratory analysis, findings during surgery, and symptoms during follow-up, including improvement and recurrence. RESULTS: The cumulative incidence rates of recurrence from 5 to 10 years after surgery were 15.4, 16.8, 19.3, 22.5, 22.5, and 22.5%, respectively. Significant differences were found between two groups in terms of age at surgery (RR: 0.764, 95% CI: 0.615-0.949, p = 0.015), duration of dysmenorrhea (RR: 1.120, 95% CI: 1.054-1.190, p < 0.001), presence of adenomyosis (RR: 1.629, 95% CI: 1.008-2.630, p = 0.046), CA125 level (RR: 1.856, 95% CI: 1.072-3.214, p = 0.021) and severity of dysmenorrhea. The severity of dysmenorrhea (RR: 1.711, 95% CI: 1.175-2.493, p = 0.005) and postoperative pregnancy (RR: 0.649, 95% CI: 0.460-0.914, p = 0.013) were significantly correlated with endometrioma recurrence in the multivariate analysis. No significant associations were found between the recurrence rate and gravida, parity, body mass index, infertility, leiomyoma presence, the size of ovarian endometrioma, the presence of deep infiltrating endometriosis, disease stage or postoperative medication. CONCLUSIONS: The severity of dysmenorrhea and postoperative pregnancy were independent risk factors for the recurrence of ovarian endometriomas after surgery during the long-time follow up.

Organo-Cation Catalyzed Asymmetric Homo/Heterodialkylation of Bisoxindoles: Construction of Vicinal All-Carbon Quaternary Stereocenters and Total Synthesis of (-)-Chimonanthidine.

A novel chiral spirocyclic amide (SPA)-derived triazolium organocatalyst has been designed and demonstrated to effect asymmetric homo- and heterodialkylations of various bisoxindoles, enabling enantioselective construction of vicinal all-carbon quaternary stereocenters. These reactions feature excellent enantio- and diastereoselectivities (up to 99% ee and >20:1 dr) as well as good to high yields (up to 89% over two steps). As an application of this methodology, the first asymmetric total synthesis of (-)-chimonanthidine has been achieved.