Discovery of novel quinoline scaffold selective estrogen receptor degraders (SERDs) for treatment of ER positive breast cancer with enhanced antiproliferative bioactivity through immunogenic cell death (ICD) effects.

Combination therapy proven to be an effective therapeutic approach for estrogen receptor (ER)-positive breast cancer. Currently, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are combined with aromatase inhibitors (AIs) or selective estrogen receptor degraders (SERDs) as first-line therapy for advanced ER-positive breast cancer. Herein, a new family of quinoline scaffold SERDs was synthesized and evaluated in MCF-7 cells. Among them, compounds 18j and 24d exhibited remarkable MCF-7 inhibition, both alone and in combination with ribociclib (CDK4/6 inhibitor), in vitro and in vivo. Meanwhile, compounds 18j and 24d effectively degraded ER and inhibited ER downstream signaling pathways. Interestingly, compounds 18j and 24d induced endoplasmic reticulum stress (ERS) and triggered immunogenic cell death (ICD) via damage-associated molecular patterns (DAMPs) in MCF-7 cells. These findings highlight the immune-related and enhanced antiproliferative effects of oral SERDs in ER positive breast cancer treatment.

Prognostic Value of Inflammatory Cytokines in Predicting Hospital Readmissions in Heart Failure with Preserved Ejection Fraction.

Purpose: The aim of this study was to explore the relationship between inflammatory cytokines and the risk of heart failure (HF) readmission in patients with heart failure with preserved ejection fraction (HFpEF). Patients and Methods: We enrolled 429 patients with HFpEF admitted to the cardiology department in our hospital from January 2020 to July 2022. The patients were divided into the readmission or non-readmission groups according to whether they were readmitted for heart failure within 1 year of discharge. The clinical features and laboratory date of the subjects were collected and analyzed. Multivariate cox regression analysis was used to identify predictors of HF readmission. In addition, receiver operating characteristic (ROC) curves were used to determine the prognostic value of each factor. Results: The levels of IL-1ß, IL-6, IL-10, IL-17, TNF-α, NT-proBNP, heart rate, total cholesterol and NYHA class were significantly higher in the readmission group than in the non-readmission group (p < 0.05). IL-1ß, IL-6, IL-17, TNF-α, NT-proBNP, heart rate and NYHA class were identified as independent predictors of HF readmission. Conclusion: Inflammatory markers, including IL-1ß, IL-6, IL-17 and TNF-α were related to the HF readmission in patients with HFpEF.

Investigating the thermal stability and calcium resistance of O/W emulsions prepared with glycosylated whey protein hydrolysates modified by different saccharides.

The poor thermal stability and ion tolerance of whey protein hydrolysates (WPH) restrict its application in emulsions, while glycosylation shows potential benefits in improving WPH stability. However, the relationship between saccharides with different Mw and the glycosylation behavior of WPH rich in short peptides is unclear. In response, the effect of different saccharides on glycosylated WPH rich in short peptides and its emulsion stability were investigated. Grafted small Mw saccharides were more beneficial to the emulsion stability of WPH. Specifically, grafting xylose effectively inhibited 121 °C sterilization and 5 mM CaCl2-induced coalescence of WPH emulsion (687.50 nm) by comprehensively enhancing steric hindrance, conformational flexibility and electrostatic repulsion, and dissociating large aggregates into small aggregates. Conversely, grafting maltodextrin (30,590 Da) reduced thermal stability of WPH emulsion (4791.80 nm) by steric shielding and bridging flocculation. These findings provide new sights into glycosylation mechanism for WPH and achieving its application in nutritional emulsions.

Sensitive sensing of GLA and ISL based on highly conductivity nitrogen-doped carbon synergistic dual-template molecularly imprinted ratiometric electrochemical sensor.

A novel ratiometric Molecularly Imprinted Electrochemical sensor for the specific marker of Glycyrrhiza glabra L. was developed in this work. To achieve simultaneous detection of two analytes on one sensor, we constructed a double template molecular imprinted electrochemical sensor with glabridin (GLA) and isoliquiritin (ISL) as templates. Further, Ferrocene/ZIF-8 (Fc/ZIF-8) composites were prepared via a one-pot solvothermal reaction and coated on the surface of a glassy carbon electrode (GCE), and the oxidation of Fc was presented as the internal reference signal. Nitrogen-doped carbon (NOC) with high conductivity was further loaded on the modified GCE. Based on theoretical exploration and computer directional simulation of density functional theory (DFT), the optimal functional monomer and the best ratio of double template molecules to functional monomer were screened. Under optimal conditions, the sensor produced electrochemical curves when exposed to a solution containing GLA and ISL. As the concentration of GLA and ISL increased, the peak current intensity of GLA and ISL (IGLA and IISL) also increased, while the peak current intensity of Fc (as a reference signal) remained relatively constant. The values of IGLA/IFc and IISL/IFc showed excellent linear relationships with GLA and ISL concentrations in the range of 0.1-160 µM and 0.5-150 µM, respectively. The detection limits were 0.052 µM and 0.27 µM (S/N = 3), respectively. Due to the imprinting effect of MIP and the existence of a reference signal, the sensor exhibited excellent selectivity and anti-interference ability and was successfully applied to the quality evaluation of Glycyrrhiza glabra L.

Impact of Oil Bodies on Structure, Rheology and Function of Acid-Mediated Soy Protein Isolate Gels.

Oil bodies (OBs) are naturally occurring pre-emulsified oil droplets that have broad application prospects in emulsions and gels. The main purpose of this research was to examine the impact of the OB content on the structure and functional aspects of acid-mediated soy protein isolate (SPI) gel filled with OBs. The results indicated that the peanut oil body (POBs) content significantly affected the water holding capacity of the gel. The rheological and textural analyses showed that POBs reduced the gel strength and hardness. The scanning electron and confocal laser scanning microscopy analyses revealed that POBs aggregated during gel formation and reduced the gel network density. The Fourier transform infrared spectrum (FTIR) analysis demonstrated that POBs participated in protein gels through hydrogen bonds, steric hindrance and hydrophobic interactions. Therefore, OBs served as inactive filler in the acid-mediated protein gel, replaced traditional oils and provided alternative ingredients for the development of new emulsion-filled gels.

Using an ER-specific optogenetic mechanostimulator to understand the mechanosensitivity of the endoplasmic reticulum.

The ability of cells to perceive and respond to mechanical cues is essential for numerous biological activities. Emerging evidence indicates important contributions of organelles to cellular mechanosensitivity and mechanotransduction. However, whether and how the endoplasmic reticulum (ER) senses and reacts to mechanical forces remains elusive. To fill the knowledge gap, after developing a light-inducible ER-specific mechanostimulator (LIMER), we identify that mechanostimulation of ER elicits a transient, rapid efflux of Ca2+ from ER in monkey kidney COS-7 cells, which is dependent on the cation channels transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and polycystin-2 (PKD2) in an additive manner. This ER Ca2+ release can be repeatedly stimulated and tuned by varying the intensity and duration of force application. Moreover, ER-specific mechanostimulation inhibits ER-to-Golgi trafficking. Sustained mechanostimuli increase the levels of binding-immunoglobulin protein (BiP) expression and phosphorylated eIF2α, two markers for ER stress. Our results provide direct evidence for ER mechanosensitivity and tight mechanoregulation of ER functions, placing ER as an important player on the intricate map of cellular mechanotransduction.

Alkylated EDTA potentiates antibacterial photodynamic activity of protoporphyrin.

Antibiotic resistance has garnered significant attention due to the scarcity of new antibiotics in development. Protoporphyrin IX (PpIX)-mediated photodynamic therapy shows promise as a novel antibacterial strategy, serving as an alternative to antibiotics. However, the poor solubility of PpIX and its tendency to aggregate greatly hinder its photodynamic efficacy. In this study, we demonstrate that alkylated EDTA derivatives (aEDTA), particularly C14-EDTA, can enhance the solubility of PpIX by facilitating its dispersion in aqueous solutions. The combination of C14-EDTA and PpIX exhibits potent antibacterial activity against Staphylococcus aureus (S. aureus) when exposed to LED light irradiation. Furthermore, this combination effectively eradicates S. aureus biofilms, which are known to be strongly resistant to antibiotics, and demonstrates high therapeutic efficacy in an animal model of infected ulcers. Mechanistic studies reveal that C14-EDTA can disrupt PpIX crystallization, increase bacterial membrane permeability and sequester divalent cations, thereby improving the accumulation of PpIX in bacteria. This, in turn, enhances reactive oxygen species (ROS) production and the antibacterial photodynamic activity. Overall, this effective strategy holds great promise in combating antibiotic-resistant strains.

Identifying Residues for Substrate Recognition in Human GPAT4 by Molecular Dynamics Simulations.

Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the first step in triacylglycerol synthesis. Understanding its substrate recognition mechanism may help to design drugs to regulate the production of glycerol lipids in cells. In this work, we investigate how the native substrate, glycerol-3-phosphate (G3P), and palmitoyl-coenzyme A (CoA) bind to the human GPAT isoform GPAT4 via molecular dynamics simulations (MD). As no experimentally resolved GPAT4 structure is available, the AlphaFold model is employed to construct the GPAT4-substrate complex model. Using another isoform, GPAT1, we demonstrate that once the ligand binding is properly addressed, the AlphaFold complex model can deliver similar results to the experimentally resolved structure in MD simulations. Following the validated protocol of complex construction, we perform MD simulations using the GPAT4-substrate complex. Our simulations reveal that R427 is an important residue in recognizing G3P via a stable salt bridge, but its motion can bring the ligand to different binding hotspots on GPAT4. Such high flexibility can be attributed to the flexible region that exists only on GPAT4 and not on GPAT1. Our study reveals the substrate recognition mechanism of GPAT4 and hence paves the way towards designing GPAT4 inhibitors.

Directional region-based feature point matching algorithm based on SURF.

Feature point matching is one of the fundamental tasks in binocular vision. It directly affects the accuracy and quality of 3D reconstruction. This study proposes a directional region-based feature point matching algorithm based on the SURF algorithm to improve the accuracy of feature point matching. First, same-name points are selected as the matching reference points in the left and right images. Then, the SURF algorithm is used to extract feature points and construct the SURF feature point descriptors. During the matching process, the location relationship between the query feature point and the reference point in the left image is directed to determine the corresponding matching region in the right image. Then, the matching is completed within this region based on Euclidean distance. Finally, the grid-based motion statistics algorithm is used to eliminate mismatches. Experimental results show that the proposed algorithm can substantially improve the matching accuracy and the number of valid matched points, particularly in the presence of a large amount of noise and interference. It also exhibits good robustness and stability.

A High-Voltage-Specialized Direct-Current Triboelectric Nanogenerator for Air Purification.

Human health and the environment face significant challenges of air pollution, which is predominantly caused by PM2.5 or PM10 particles. Existing control methods often require elevated energy consumption or bulky high-voltage electrical equipment. To overcome these limitations, a self-powered, convenient, and compact direct current high-voltage triboelectric nanogenerator based on triboelectrification and electrostatic breakdown effects is proposed. By optimizing the structure-design of the direct current triboelectric nanogenerator and corresponding output voltage, it can easily achieve an output voltage of over 3 kV with a high charge density of 320 µC m-2 . A power management circuit is designed to overcome the influence of third domain self-breakdown, optimize 92.5% amplitude of voltage shake, and raise 5% charge utilization ratio. With a device size as tiny as 2.25 cm3 , it can continuously drive carbon nanowires to generate negative ions that settle dust within 300 s. This compact, simple, efficient, and safe high-voltage direct current triboelectric nanogenerator represents a promising sustainable solution. It offers efficient dust mitigation, fostering cleaner environments, and enhancing overall health.

Biochar affects compressive strength of Portland cement composites: a meta-analysis.

One strategy to reduce CO2 emissions from cement production is to reduce the amount of Portland cement produced by replacing it with supplementary cementitious materials (SCMs). Biochar is a potential SCM that is an eco-friendly and stable porous pyrolytic material. However, the effects of biochar addition on the performances of Portland cement composites are not fully understood. This meta-analysis investigated the impact of biochar addition on the 7- and 28-day compressive strength of Portland cement composites based on 606 paired observations. Biochar feedstock type, pyrolysis conditions, pre-treatments and modifications, biochar dosage, and curing type all influenced the compressive strength of Portland cement composites. Biochars obtained from plant-based feedstocks (except rice and hardwood) improved the 28-day compressive strength of Portland cement composites by 3-13%. Biochars produced at pyrolysis temperatures higher than 450 °C, with a heating rate of around 10 C min-1, increased the 28-day compressive strength more effectively. Furthermore, the addition of biochar with small particle sizes increased the compressive strength of Portland cement composites by 2-7% compared to those without biochar addition. Biochar dosage of < 2.5% of the binder weight enhanced both compressive strengths, and common curing methods maintained the effect of biochar addition. However, when mixing the cement, adding fine and coarse aggregates such as sand and gravel affects the concrete and mortar's compressive strength, diminishing the effect of biochar addition and making the biochar effect nonsignificant. We concluded that appropriate biochar addition could maintain or enhance the mechanical performance of Portland cement composites, and future research should explore the mechanisms of biochar effects on the performance of cement composites. Supplementary Information: The online version contains supplementary material available at 10.1007/s42773-024-00309-2.

Cognitive impairment in Chinese traumatic brain injury patients: from challenge to future perspectives.

Traumatic Brain Injury (TBI) is a prevalent form of neurological damage that may induce varying degrees of cognitive dysfunction in patients, consequently impacting their quality of life and social functioning. This article provides a mini review of the epidemiology in Chinese TBI patients and etiology of cognitive impairment. It analyzes the risk factors of cognitive impairment, discusses current management strategies for cognitive dysfunction in Chinese TBI patients, and summarizes the strengths and limitations of primary testing tools for TBI-related cognitive functions. Furthermore, the article offers a prospective analysis of future challenges and opportunities. Its objective is to contribute as a reference for the prevention and management of cognitive dysfunction in Chinese TBI patients.

Force-induced tail-autotomy mitochondrial fission and biogenesis of matrix-excluded mitochondrial-derived vesicles for quality control.

Mitochondria constantly fuse and divide for mitochondrial inheritance and functions. Here, we identified a distinct type of naturally occurring fission, tail-autotomy fission, wherein a tail-like thin tubule protrudes from the mitochondrial body and disconnects, resembling autotomy. Next, utilizing an optogenetic mitochondria-specific mechanostimulator, we revealed that mechanical tensile force drives tail-autotomy fission. This force-induced fission involves DRP1/MFF and endoplasmic reticulum tubule wrapping. It redistributes mitochondrial DNA, producing mitochondrial fragments with or without mitochondrial DNA for different fates. Moreover, tensile force can decouple outer and inner mitochondrial membranes, pulling out matrix-excluded tubule segments. Subsequent tail-autotomy fission separates the matrix-excluded tubule segments into matrix-excluded mitochondrial-derived vesicles (MDVs) which recruit Parkin and LC3B, indicating the unique role of tail-autotomy fission in segregating only outer membrane components for mitophagy. Sustained force promotes fission and MDV biogenesis more effectively than transient one. Our results uncover a mechanistically and functionally distinct type of fission and unveil the role of tensile forces in modulating fission and MDV biogenesis for quality control, underscoring the heterogeneity of fission and mechanoregulation of mitochondrial dynamics.

Comparative prognosis and risk assessment in gallbladder neuroendocrine neoplasms versus adenocarcinomas.

Background: Gallbladder neuroendocrine neoplasms (GB-NENs) are a rare malignant disease, with most cases diagnosed at advanced stages, often resulting in poor prognosis. However, studies regarding the prognosis of this condition and its comparison with gallbladder adenocarcinomas (GB-ADCs) have yet to yield convincing conclusions. Methods: We extracted cases of GB-NENs and GB-ADCs from the Surveillance, Epidemiology, and End Results (SEER) database in the United States. Firstly, we corrected differences in clinical characteristics between the two groups using propensity score matching (PSM). Subsequently, we visualized and compared the survival outcomes of the two groups using the Kaplan-Meier method. Next, we employed the least absolute shrinkage and selection operator (LASSO) regression and Cox regression to identify prognostic factors for GB-NENs and constructed two nomograms for predicting prognosis. These nomograms were validated with an internal validation dataset from the SEER database and an external validation dataset from a hospital. Finally, we categorized patients into high-risk and low-risk groups based on their overall survival (OS) scores. Results: A total of 7,105 patients were enrolled in the study, comprising 287 GB-NENs patients and, 6,818 GB-ADCs patients. There were substantial differences in clinical characteristics between patients, and GB-NENs exhibited a significantly better prognosis. Even after balancing these differences using PSM, the superior prognosis of GB-NENs remained evident. Independent prognostic factors selected through LASSO and Cox regression were age, histology type, first primary malignancy, tumor size, and surgery. Two nomograms for prognosis were developed based on these factors, and their performance was verified from three perspectives: discrimination, calibration, and clinical applicability using training, internal validation, and external validation datasets, all of which exhibited excellent validation results. Using a cutoff value of 166.5 for the OS nomogram score, patient mortality risk can be identified effectively. Conclusion: Patients with GB-NENs have a better overall prognosis compared to those with GB-ADCs. Nomograms for GB-NENs prognosis have been effectively established and validated, making them a valuable tool for assessing the risk of mortality in clinical practice.

Mechanism exploration and biomarker identification of glycemic deterioration in patients with diseases of the exocrine pancreas.

The damage to the endocrine pancreas among patients with diseases of the exocrine pancreas (DP) leads to reduced glycemic deterioration, ultimately resulting in diabetes of the exocrine pancreas (DEP). The present research aims to investigate the mechanism responsible for glycemic deterioration in DP patients, and to identify useful biomarkers, with the ultimate goal of enhancing clinical practice awareness. Gene expression profiles of patients with DP in this study were acquired from the Gene Expression Omnibus database. The original study defines DP patients to belong in one of three categories: non-diabetic (ND), impaired glucose tolerance (IGT) and DEP, which correspond to normoglycemia, early and late glycemic deterioration, respectively. After ensuring quality control, the discovery cohort included 8 ND, 20 IGT, and 12 DEP, while the validation cohort included 27 ND, 15 IGT, and 20 DEP. Gene set enrichment analysis (GSEA) employed differentially expressed genes (DEGs), while immunocyte infiltration was determined using single sample gene set enrichment analysis (ssGSEA). Additionally, correlation analysis was conducted to establish the link between clinical characteristics and immunocyte infiltration. The least absolute shrinkage and selection operator regression and random forest combined to identify biomarkers indicating glycemic deterioration in DP patients. These biomarkers were further validated through independent cohorts and animal experiments. With glycemic deterioration, biological processes in the pancreatic islets such as nutrient metabolism and complex immune responses are disrupted in DP patients. The expression of ACOT4, B2M, and ACKR2 was upregulated, whereas the expression of CACNA1F was downregulated. Immunocyte infiltration in the islet microenvironment showed a significant positive correlation with the age, body mass index (BMI), HbA1c and glycemia at the 2-h of patients. It was a crucial factor in glycemic deterioration. Additionally, B2M demonstrated a significant positive correlation with immunocyte infiltration and clinical features. Quantitative real-time PCR (qRT-PCR) and western blotting confirmed the upregulation in B2M. Immunofluorescent staining suggested the alteration of B2M was mainly in the alpha cells and beta cells. Overall, the study showed that gradually increased immunocyte infiltration was a significant contributor to glycemic deterioration in patients with DP, and it also highlighted B2M as a biomarker.

Multi-Functional Formaldehyde-Nitrate Batteries for Wastewater Refining, Electricity Generation, and Production of Ammonia and Formate.

As bulky pollutants in industrial and agricultural wastewater, nitrate and formaldehyde pose serious threats to the human health and ecosystem. Current purification technologies including chemical and bio-/photo-/electro-chemical methods, are generally high-cost, time-consuming, or energy-intensive. Here, we report a novel formaldehyde-nitrate battery by pairing anodic formaldehyde oxidation with cathodic nitrate reduction, which simultaneously enables wastewater purification, electricity generation, and the production of high-value-added ammonia and formate. As a result, the formaldehyde-nitrate battery remarkably exhibits an open-circuit voltage of 0.75 V, a peak power density of 3.38 mW cm-2 and the yield rates of 32.7 mg h-1 cm-2 for ammonia and 889.4 mg h-1 cm-2 for formate. In a large-scale formaldehyde-nitrate battery (25 cm2 ), 99.9 % of nitrate and 99.8 % of formaldehyde are removed from simulated industrial wastewater and the electricity of 2.03 W⋅h per day is generated. Moreover, the design of such a multi-functional battery is universally applicable to the coupling of NO3 - or NO2 - reduction with various aldehyde oxidization, paving a new avenue for wastewater purification and chemical manufacturing.

Multimodality management for chronic subdural hematoma in China: protocol and characteristics of an ambidirectional, nationwide, multicenter registry study.

BACKGROUND: Despite its prevalence, there is ongoing debate regarding the optimal management strategy for chronic subdural hematoma (CSDH), reflecting the variability in clinical presentation and treatment outcomes. This ambidirectional, nationwide, multicenter registry study aims to assess the efficacy and safety of multimodality treatment approaches for CSDH in the Chinese population. METHODS/DESIGN: A multicenter cohort of CSDH patients from 59 participating hospitals in mainland China was enrolled in this study. The treatment modalities encompassed a range of options and baseline demographics, clinical characteristics, radiographic findings, and surgical techniques were documented. Clinical outcomes, including hematoma resolution, recurrence rates, neurological status, and complications, were assessed at regular intervals during treatment, 3 months, 6 months, 1 year, and 2 years follow-up. RESULT: Between March 2022 and August 2023, a comprehensive cohort comprising 2173 individuals who met the criterion was assembled across 59 participating clinical sites. Of those patients, 81.1% were male, exhibiting an average age of 70.12 ± 14.53 years. A historical record of trauma was documented in 48.0% of cases, while headache constituted the predominant clinical presentation in 58.1% of patients. The foremost surgical modality employed was the burr hole (61.3%), with conservative management accounting for 25.6% of cases. Notably, a favorable clinical prognosis was observed in 88.9% of CSDH patients at 3 months, and the recurrence rate was found to be 2.4%. CONCLUSION: This registry study provides critical insights into the multimodality treatment of CSDH in China, offering a foundation for advancing clinical practices, optimizing patient management, and ultimately, improving the quality of life for individuals suffering from this challenging neurosurgical condition. TRIAL REGISTRATION: ChiCTR2200057179.

Macrophage-membrane-coated hybrid nanoparticles with self-supplied hydrogen peroxide for enhanced chemodynamic tumor therapy.

Addressing the challenges of chemodynamic therapies (CDTs) relying on Fenton reactions in malignant tumors is an active research area. Here, we report a method to develop pH-responsive hybrid nanoparticles for enhanced chemodynamic tumor treatment. Reactive CaO2 nanoparticles (core) are isolated by biocompatible ZIF-8 doped with Fe2+ (shell), and then encapsulated by macrophage membranes (symbolized as CaO2@Fe-ZIF-8@macrophage membrane or CFZM), thus endowed with high stability under normal physiological conditions. Our design features active tumor-homing by the macrophage-membrane coating, tumor microenvironment (TME)-responsive cargo release, and self-supplied hydrogen peroxide for promotion of the Fenton reaction. We demonstrate the improved delivery/tumor cell uptake of CFZM, the efficient production of toxic ˙OH with self-supplied H2O2 in CFZM, and high-efficacy tumor ablation on BALB/c mice bearing CT26 tumor cells. This offers a translational strategy to develop active tumor-targeting and TME-responsive nanotherapeutics with enhanced CDT against malignant tumors.

Single-cell and transcriptomic analyses reveal the influence of diabetes on ovarian cancer.

BACKGROUND: There has been a significant surge in the global prevalence of diabetes mellitus (DM), which increases the susceptibility of individuals to ovarian cancer (OC). However, the relationship between DM and OC remains largely unexplored. The objective of this study is to provide preliminary insights into the shared molecular regulatory mechanisms and potential biomarkers between DM and OC. METHODS: Multiple datasets from the GEO database were utilized for bioinformatics analysis. Single cell datasets from the GEO database were analysed. Subsequently, immune cell infiltration analysis was performed on mRNA expression data. The intersection of these datasets yielded a set of common genes associated with both OC and DM. Using these overlapping genes and Cytoscape, a protein‒protein interaction (PPI) network was constructed, and 10 core targets were selected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then conducted on these core targets. Additionally, advanced bioinformatics analyses were conducted to construct a TF-mRNA-miRNA coregulatory network based on identified core targets. Furthermore, immunohistochemistry staining (IHC) and real-time quantitative PCR (RT-qPCR) were employed for the validation of the expression and biological functions of core proteins, including HSPAA1, HSPA8, SOD1, and transcription factors SREBF2 and GTAT2, in ovarian tumors. RESULTS: The immune cell infiltration analysis based on mRNA expression data for both DM and OC, as well as analysis using single-cell datasets, reveals significant differences in mononuclear cell levels. By intersecting the single-cell datasets, a total of 119 targets related to mononuclear cells in both OC and DM were identified. PPI network analysis further identified 10 hub genesincludingHSP90AA1, HSPA8, SNRPD2, UBA52, SOD1, RPL13A, RPSA, ITGAM, PPP1CC, and PSMA5, as potential targets of OC and DM. Enrichment analysis indicated that these genes are primarily associated with neutrophil degranulation, GDP-dissociation inhibitor activity, and the IL-17 signaling pathway, suggesting their involvement in the regulation of the tumor microenvironment. Furthermore, the TF-gene and miRNA-gene regulatory networks were validated using NetworkAnalyst. The identified TFs included SREBF2, GATA2, and SRF, while the miRNAs included miR-320a, miR-378a-3p, and miR-26a-5p. Simultaneously, IHC and RT-qPCR reveal differential expression of core targets in ovarian tumors after the onset of diabetes. RT-qPCR further revealed that SREBF2 and GATA2 may influence the expression of core proteins, including HSP90AA1, HSPA8, and SOD1. CONCLUSION: This study revealed the shared gene interaction network between OC and DM and predicted the TFs and miRNAs associated with core genes in monocytes. Our research findings contribute to identifying potential biological mechanisms underlying the relationship between OC and DM.

Lewis Acidic Metal-Organic Framework Assisted Ambient Liquid Extraction Mass Spectrometry Imaging for Enhancing the Coverage of Poorly Ionizable Lipids in Brain Tissue.

The spatial distribution of lipidomes in tissues is of great importance in studies of living processes, diseases, and therapies. Mass spectrometry imaging (MSI) has become a critical technique for spatial lipidomics. However, MSI of low-abundance or poorly ionizable lipids is still challenging because of the ion suppression from high-abundance lipids. Here, a metal-organic framework (MOF) Zr6O4(OH)4(1,3,5-Tris(4-carboxyphenyl) benzene)2(triflate)6(Zr6OTf-BTB) was prepared and used for selective on-tissue adsorption of phospholipids to reduce ion suppression from them to poorly ionizable lipids. The results show that Zr6OTf-BTB with strong Lewis acidic sites and a large specific surface area (647.9 m2·g-1) could selectively adsorb phospholipids under 1% FA-MeOH. Adsorption efficiencies of phospholipids are 88.4-144.9 times higher than those of other neutral lipids. Moreover, the adsorption capacity and the adsorption kinetic rate constant of the new material to phospholipids are higher than those of Zr6-BTB (242.72 vs 73.96 mg·g-1, 0.0442 vs 0.0220 g·mg-1·min-1). A Zr6OTf-BTB sheet was prepared by a lamination technique for on-tissue phospholipid adsorption from brain tissue. Then, the tissue section on the Zr6OTf-BTB sheet was directly imaged via ambient liquid extraction-MSI with 1% FA-MeOH as the sampling solvent. The results showed that phospholipids could be 100% removed directly on tissue, and the detection coverage of the Zr6OTf-BTB-enhanced MSI method to ceramides (Cers) and hexosylceramides (HexCers) was increased by 5-26 times compared with direct tissue MSI (26 vs 1 and 17 vs 3). The new method provides an efficient and convenient way to eliminate the ion suppression from phospholipids in MSI, largely improving the detection coverage of low-abundance and poorly ionizable lipids.