ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis.

Herein, we elucidate the potential role of ANO6 (TMEM16F) in gastrointestinal stromal tumors (GISTs). ANO6 expression in GIST and adjacent normal tissues was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cell proliferation, apoptosis, and pyroptosis were examined utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, terminal deoxynucleotidyl transferase dUTP Nick-End Labeling staining, and flow cytometry. In addition, the total iron and Fe2+ levels were assessed. IL-18 and IL-1ß levels were also evaluated. Lipid reactive oxygen species (ROS), cystine (Cys), glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels were evaluated using appropriate kits. Ferroptotic markers, including Ptgs2, Chac1, SLC7A11, and SLC3A2, were analyzed by RT-qPCR, western blotting, and immunohistochemistry. ANO6 expression decreased in GIST tissues. ANO6-plasmid inhibits proliferation, induces apoptosis, and promotes pyroptosis in GIST-T1 and GIST-T1 IR cells. The ANO6-plasmid induced ferroptosis, as confirmed by enhanced lipid ROS levels, increased intracellular concentrations of total iron and Fe2+, promoted Ptgs2 and Chac1 expression, reduced Cys, GSH, and GPX4 levels, and downregulated SLC7A11 and SLC3A2 expression after in vitro and in vivo treatment with ANO6-plasmid. Moreover, the ANO6-plasmid inhibited GIST growth in vivo. Therefore, ANO6 may be a promising therapeutic target for blocking the development of GIST via the induction of apoptosis, pyroptosis, and ferroptosis.

Impact of sequential (first- to third-generation) EGFR-TKI treatment on corrected QT interval in NSCLC patients.

Objective: To evaluate the impact of sequential (first- to third-generation) epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment on top-corrected QT interval (top-QTc) in non-small cell lung cancer (NSCLC) patients. Methods: We retrospectively reviewed the medical records of NSCLC patients undergoing sequential EGFR-TKI treatment at Shanghai Chest Hospital between October 2016 and August 2021. The heart rate (HR), top-QT interval, and top-QTc of their ECGs were extracted from the institutional database and analyzed. Logistic regression was performed to identify predictors for top-QTc prolongation. Results: Overall, 228 patients were enrolled. Compared with baseline (median, 368 ms, same below), both first-generation (376 ms vs. 368 ms, p < 0.001) and sequential third-generation EGFR-TKIs (376 ms vs. 368 ms, p = 0.002) prolonged top-QT interval to a similar extent (p = 0.635). Top-QTc (438 ms vs. 423 ms, p < 0.001) and HR (81 bpm vs.79 bpm, p = 0.008) increased after first-generation EGFR-TKI treatment. Further top-QTc prolongation (453 ms vs. 438 ms, p < 0.001) and HR increase (88 bpm vs. 81 bpm, p < 0.001) occurred after treatment advanced. Notably, as HR elevated during treatment, top-QT interval paradoxically increased rather than decreased, and the top-QTc increased rather than slightly fluctuated. Moreover, such phenomena were more significant after treatment advanced. After adjusting for confounding factors, pericardial effusion and lower serum potassium levels were independent predictors of additional QTc prolongation during sequential third-generation EGFR-TKI treatment. Conclusion: First-generation EGFR-TKI could prolong top-QTc, and sequential third-generation EGFR-TKI induced further prolongation. Top-QT interval paradoxically increased and top-QTc significantly increased as HR elevated, which was more significant after sequential EGFR-TKI treatment. Pericardial effusion and lower serum potassium levels were independent predictors of additional QTc prolongation after sequential EGFR-TKI treatment.

The role of small RNAs in resistant melon cultivar against Phelipanche aegyptiaca parasitization.

Bidirectional trans-kingdom RNA silencing, a pivotal factor in plant-pathogen interactions, remains less explored in plant host-parasite dynamics. Here, using small RNA sequencing in melon root systems, we investigated microRNA (miRNA) expression variation in resistant and susceptible cultivars pre-and post-infection by the parasitic plant, broomrape. This approach revealed 979 known miRNAs and 110 novel miRNAs across 110 families. When comparing susceptible (F0) and resistant (R0) melon lines with broomrape infection (F25 and R25), 39 significantly differentially expressed miRNAs were observed in F25 vs. F0, 35 in R25 vs. R0, and 5 in R25 vs. F25. Notably, two miRNAs consistently exhibited differential expression across all comparisons, targeting genes linked to plant disease resistance. This suggests their pivotal role in melon's defense against broomrape. The target genes of these miRNAs were confirmed via degradome sequencing and validated by qRT-PCR, ensuring reliable sequencing outcomes. GO and KEGG analyses shed light on the molecular functions and pathways of these differential miRNAs. Furthermore, our study unveiled four trans-kingdom miRNAs, forming a foundation for exploring melon's resistance to broomrape.

Perioperative outcomes and survival of modified subxiphoid video-assisted thoracoscopic surgery thymectomy for T2-3 thymic malignancies: A retrospective comparison study.

OBJECTIVE: Our previous study demonstrated that modified subxiphoid video-assisted thoracic surgery thymectomy with an auxiliary sternal retractor is feasible for locally invasive thymic malignancies. This study aimed to compare perioperative and oncological outcomes of modified subxiphoid video-assisted thoracoscopic surgery thymectomy versus median sternotomy thymectomy for locally advanced thymic malignancies. METHODS: In total, 221 patients with T2-3 thymic malignancies who underwent modified subxiphoid video-assisted thoracoscopic surgery thymectomy or median sternotomy thymectomy between 2015 and 2020 were enrolled in our prospectively maintained database. A 1:1 propensity score-matching analysis was performed to balance the bias. Surgical difficulty was evaluated with a modified resection index. Perioperative and oncological results were compared between the modified subxiphoid video-assisted thoracoscopic surgery thymectomy group and the median sternotomy thymectomy group. RESULTS: There were 72 patients in each group in the final analysis. Our results showed that the modified subxiphoid video-assisted thoracoscopic surgery thymectomy group had a shorter operative duration (98 vs 129 minutes, P < .001), less blood loss (40 vs 100 mL, P < .001), shorter drainage duration (3 vs 5 days, P < .001), shorter length of hospital stay (5 vs 6 days, P < .001), and fewer postoperative complications (5.6% vs 23.6%; P = .005). No significant difference was detected in complete resection (98.6% vs 98.6%, P = 1.000) between the 2 groups. Conversion occurred in 5 of 106 patients (4.7%). Survival analyses indicated similar recurrence-free survival (hazard ratio, 0.94; 95% CI, 0.40-2.20; P = .883) and overall survival (hazard ratio, 0.52; 95% CI, 0.05-5.02; P = .590) between the 2 groups. CONCLUSIONS: Modified subxiphoid video-assisted thoracoscopic surgery thymectomy was safe and effective for T2-3 thymic malignancies and could be an alternative for selected patients with locally advanced thymic diseases. Further prospective studies are needed to evaluate the long-term survival of those undergoing modified subxiphoid approach thoracoscopic thymectomy.

Optimized Antibiotic Resistance Genes Monitoring Scenarios Promote Sustainability of Urban Water Cycle.

Dissemination of antibiotic resistance genes (ARGs) in urban water bodies has become a significant environmental and health concern. Many approaches based on real-time quantitative PCR (qPCR) have been developed to offer rapid and highly specific detection of ARGs in water environments, but the complicated and time-consuming procedures have hindered their widespread use. Herein, we developed a facile one-step approach for rapid detection of ARGs by leveraging the trans-cleavage activity of Cas12a and recombinase polymerase amplification (RPA). This efficient method matches the sensitivity and specificity of qPCR and requires no complex equipment. The results show a strong correlation between the prevalence of four ARG markers (ARGs: sul1, qnrA-1, mcr-1, and class 1 integrons: intl1) in tap water, human urine, farm wastewater, hospital wastewater, municipal wastewater treatment plants (WWTPs), and proximate natural aquatic ecosystems, indicating the circulation of ARGs within the urban water cycle. Through monitoring the ARG markers in 18 WWTPs in 9 cities across China during both peak and declining stages of the COVID epidemic, we found an increased detection frequency of mcr-1 and qnrA-1 in wastewater during peak periods. The ARG detection method developed in this work may offer a useful tool for promoting a sustainable urban water cycle.

Status and influencing factors of nurses' burnout: A cross-sectional study during COVID-19 regular prevention and control in Jiangsu Province, China.

Background: Chinese nurses working with immense stress may have issues with burnout during COVID-19 regular prevention and control. There were a few studies investigating status of burnout and associated factors among Chinese nurses. However, the relationships remained unclear. Objectives: To investigate status and associated factors of nurses' burnout during COVID-19 regular prevention and control. Methods: 784 nurses completed questionnaires including demographics, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Insomnia Severity Index, Impact of Event Scale-revised, Perceived Social Support Scale, Connor-Davidson Resilience Scale, General Self-efficacy Scale and Maslach Burnout Inventory. Results: 310 (39.5%), 393 (50.1%) and 576 (73.5%) of respondents were at high risk of emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (PA). The risk of EE, DP and reduced PA were moderate, high and high. Nurses with intermediate and senior professional rank and title and worked >40 h every week had lower scores in EE. Those worked in low-risk department reported lower scores in PA. Anxiety, post-traumatic stress disorder (PTSD), self-efficacy and social support were influencing factors of EE and DP, while social support and resilience were associated factors of PA. Conclusion: Chinese nurses' burnout during COVID-19 regular prevention and control was serious. Professional rank and title, working unit, weekly working hours, anxiety, PTSD, self-efficacy, social support and resilience were associated factors of burnout.

Transformation of Coherent Twin Boundary into Basal-Prismatic Boundary in HCP-Ti: A Molecular Dynamics Study.

The manufacturing process for wrought Ti alloys with the hexagonal close-packed (HCP) structure introduces a complicated microstructure with abundant intra- and inter-grain boundaries, which greatly influence performance. In the hexagonal close-packed (HCP) structure, two types of grain boundaries are commonly observed between grains with ~90° misorientation: the basal/prismatic boundary (BPB) and the coherent twin boundary (CTB). The mechanical response of the BPB and CTB under external loading was studied through molecular dynamic simulations of HCP-Ti. The results revealed that CTB undergoes transformation into BPB through the accumulation of twin boundary (TB) steps and subsequent emission of Shockley partial dislocations. When the total mismatch vector is close to the Burgers vector of a Shockley partial dislocation, BPB emits partial dislocations and further grows along the stacking faults. When a pair of CTBs are close to each other, severe boundary distortion occurs, facilitating the emission and absorption of partial dislocations, which further assists the CTB-BPB transformation. The present results thus help to explain the frequent observation of coexisting CTB and BPB in HCP alloys and further contribute to the understanding of their microstructure and property regulation.

Reconstructing Kaolinite Compounds for Remarkably Enhanced Adsorption of Congo Red.

Organic dyes are widely used in many important areas, but they also bring many issues for water pollution. To address the above issues, a reconstructed kaolinite hybrid compound (γ-AlOOH@A-Kaol) was obtained from raw kaolinite (Kaol) in this work. The product was then characterized by X-ray diffraction (XRD), Fourier-transform infrared (ATR-FTIR), Brunauer-Emmett-Teller (BET), and scanning electron microscopy (SEM), and the absorption properties of γ-AlOOH@A-Kaol for congo red were further studied. The results demonstrated that flower-like γ-AlOOH with nanolamellae were uniformly loaded on the surface of acid-treated Kaol with a porous structure (A-Kaol). In addition, the surface area (36.5 m2/g), pore volume (0.146 cm3/g), and pore size (13.0 nm) of γ-AlOOH@A-Kaol were different from those of A-Kaol (127.4 m2/g, 0.127 cm3/g, and 4.28 nm, respectively) and γ-AlOOH (34.1 m2/g, 0.315 cm3/g, and 21.5 nm, respectively). The unique structure could significantly enhance the sorption capacity for congo red, which could exceed 1000 mg/g. The reasons may be ascribed to the abundant groups of -OH, large specific surface area, and porous structure of γ-AlOOH@A-Kaol. This work provides an efficient route for comprehensive utilization and production of Kaol-based compound materials that could be used in the field of environmental conservation.

Preparation of a Polymeric Phosphoramide Flame-Retardant and Its Effect on the Flame-Retardant Properties of Epoxy Resin.

The flammability of epoxy resins and knowing how to achieve curing are particularly important factors during use. A novel approach for enhancing the fire resistance and reducing the smoke emission of epoxy resin during the curing process is suggested, which involves the utilization of a three-source integrated polymerization intumescent flame-retardant. In this study, the synthesis of poly 4,4-diaminodiphenylsulfone spirocyclic pentaerythritol bisphosphonate (PCS) is achieved through using solution polymerization, utilizing 4,4'-diaminodiphenylsulfone (DDS) and spirocyclic pentaerythritol bisphosphorate disphosphoryl chloride (SPDPC) as initial components. Following that, the EP underwent the inclusion of PCS to examine its resistance to heat, its ability to prevent flames, its effectiveness in reducing smoke and its curing effect. Compared to the unmodified epoxy resin, the addition of PCS can not only cure the epoxy resin, but also decompose before the epoxy resin and has a good carbonization effect. With the addition of 7 wt.% PCS, the LOI value can achieve 31.2% and successfully pass the UL-94 test with a V-0 rating. Moreover, the cone calorimeter experiment demonstrated a noteworthy decline of 59.7% in the maximum heat release rate (pHRR), 63.7% in overall heat release (THR), and 42.3% in total smoke generation (TSP). Based on the examination of TG-FTIR and SEM findings, there is ample evidence to suggest that PCS, functioning as a phosphorus-nitrogen intumescent flame-retardant that combines three origins, has the potential to exhibit a favorable flame-retardant impact in both its gas and condensed phases.

Development and Validation of an Explainable Deep Learning Model to Predict In-Hospital Mortality for Patients With Acute Myocardial Infarction: Algorithm Development and Validation Study.

BACKGROUND: Acute myocardial infarction (AMI) is one of the most severe cardiovascular diseases and is associated with a high risk of in-hospital mortality. However, the current deep learning models for in-hospital mortality prediction lack interpretability. OBJECTIVE: This study aims to establish an explainable deep learning model to provide individualized in-hospital mortality prediction and risk factor assessment for patients with AMI. METHODS: In this retrospective multicenter study, we used data for consecutive patients hospitalized with AMI from the Chongqing University Central Hospital between July 2016 and December 2022 and the Electronic Intensive Care Unit Collaborative Research Database. These patients were randomly divided into training (7668/10,955, 70%) and internal test (3287/10,955, 30%) data sets. In addition, data of patients with AMI from the Medical Information Mart for Intensive Care database were used for external validation. Deep learning models were used to predict in-hospital mortality in patients with AMI, and they were compared with linear and tree-based models. The Shapley Additive Explanations method was used to explain the model with the highest area under the receiver operating characteristic curve in both the internal test and external validation data sets to quantify and visualize the features that drive predictions. RESULTS: A total of 10,955 patients with AMI who were admitted to Chongqing University Central Hospital or included in the Electronic Intensive Care Unit Collaborative Research Database were randomly divided into a training data set of 7668 (70%) patients and an internal test data set of 3287 (30%) patients. A total of 9355 patients from the Medical Information Mart for Intensive Care database were included for independent external validation. In-hospital mortality occurred in 8.74% (670/7668), 8.73% (287/3287), and 9.12% (853/9355) of the patients in the training, internal test, and external validation cohorts, respectively. The Self-Attention and Intersample Attention Transformer model performed best in both the internal test data set and the external validation data set among the 9 prediction models, with the highest area under the receiver operating characteristic curve of 0.86 (95% CI 0.84-0.88) and 0.85 (95% CI 0.84-0.87), respectively. Older age, high heart rate, and low body temperature were the 3 most important predictors of increased mortality, according to the explanations of the Self-Attention and Intersample Attention Transformer model. CONCLUSIONS: The explainable deep learning model that we developed could provide estimates of mortality and visual contribution of the features to the prediction for a patient with AMI. The explanations suggested that older age, unstable vital signs, and metabolic disorders may increase the risk of mortality in patients with AMI.

The loss of dissolved organic matter from biological soil crust at various successional stages under rainfall of different intensities: Insights into the changes of molecular components at different rainfall stages.

Biological soil crusts (BSCs) are typical covers in arid and semiarid regions. The dissolved organic matter (DOM) of BSCs can be transported to various aquatic ecosystems by rainfall-runoff processes. However, the spatiotemporal variation in quality and quantity of DOM in runoff remains unclear. Herein, four kinds of runoff plots covered by four successional stages of BSCs were set up on slopes, including bare runoff plot (BR), cyanobacteria crust covered runoff plot (CR), mixed crust covered runoff plot (MIR), and moss crust covered runoff plot (MOR). The quantity and quality of DOM in runoff during rainfall was investigated based on the stimulated rainfall experiments combined with optical spectroscopy and ultra-high resolution mass spectrometry analyses. The results showed that the DOM concentrations (i.e., 0.30 to 45.25 mg L-1) in runoff followed the pattern of MOR>MIR>CR>BR, and they were exponentially decreased with rainfall duration. The DOM loss rate of BR (8.26 to 11.64 %) was significantly greater than those of CR, MIR, and MOR (0.84 to 3.22 %). Highly unsaturated compounds (HUCs), unsaturated aliphatic compounds (UACs), saturated compounds (SCs), and peptide-like compounds (PLCs) were the dominated compounds of the water extractable DOM from the original soils. Thereinto, PLCs and UACs were more easily leached into runoff during rainfall. The relatively intensity of HUCs in runoff generally decreased with rainfall duration, while the relatively intensities of UACs, PLCs, and SCs slightly increased with rainfall duration. These findings suggested that the DOM loss rate was effectively decreased with the successional of BSCs during rainfall; meanwhile, some labile compounds (e.g., PLCs and UACs) were transported into various aquatic ecosystems by rainfall-runoff processes.

Hybrid supercapacitors using metal-organic framework derived nickel-sulfur compounds.

HYPOTHESIS: Metal-organic frameworks (MOFs) are highly suitable precursors for supercapacitor electrode materials owing to their high porosity and stable backbone structures that offer several advantages for redox reactions and rapid ion transport. EXPERIMENTS: In this study, a carbon-coated Ni9S8 composite (Ni9S8@C-5) was prepared via sulfuration at 500 ℃ using a spherical Ni-MOF as the sacrificial template. FINDING: The stable carbon skeleton derived from Ni-MOF and positive structure-activity relationship due to the multinuclear Ni9S8 components resulted in a specific capacity of 278.06 mAh·g-1 at 1 A·g-1. Additionally, the hybrid supercapacitor (HSC) constructed using Ni9S8@C-5 as the positive electrode and the laboratory-prepared coal pitch-based activated carbon (CTP-AC) as the negative electrode achieved an energy density of 69.32 Wh·kg-1 at a power density of 800.06 W·kg-1, and capacity retention of 83.06 % after 5000 cycles of charging and discharging at 5 A·g-1. The Ni-MOF sacrificial template method proposed in this study effectively addresses the challenges associated with structural collapse and agglomeration of Ni9S8 during electrochemical reactions, thus improving its electrochemical performance. Hence, a simple preparation method is demonstrated, with broad application prospects in supercapacitor electrodes.

Synthesis of N-propanol from CO2 Electroreduction on Bicontinuous Cu2O/Cu Nanodomains.

n-propanol is an important pharmaceutical and pesticide intermediate. To produce n-propanol by electrochemical reduction of CO2 is a promising way, but is largely restricted by the very low selectivity and activity. How to promote the coupling of *C1 and *C2 intermediates to form the *C3 intermediate for n-propanol formation is challenging. Here, we propose the construction of bicontinuous structure of Cu2O/Cu electrocatalyst, which consists of ultra-small Cu2O nanodomains, Cu nanodomains and large amounts of grain boundaries between Cu2O and Cu nanodomains. The n-propanol current density is as high as 101.6 mA cm-2 at the applied potential of -1.1 V vs. reversible hydrogen electrode in flow cell, with the Faradaic efficiency up to 12.1%. Moreover, the catalyst keeps relatively stable during electrochemical CO2 reduction process. Experimental studies and theoretical calculations reveal that the bicontinuous structure of Cu2O/Cu can facilitate the *CO formation, *CO-*CO coupling and *CO-*OCCO coupling for the final generation of n-propanol.

Improvements in advanced hepatocellular carcinoma to repeat implementation of primary protocol after cancer progression occurs following sequential systemic therapy and a clinical trial: A case report.

INTRODUCTION: Systemic therapy is recommended for patients with advanced hepatocellular carcinoma (aHCC). However, drug resistance occurs over time when patients receive systemic therapy, resulting in cancer progression. Due to the lack of relevant clinical trials, optimizing subsequent treatments after cancer progression remains elusive. PATIENT CONCERNS: A 52-year-old male patient presented with epigastric discomfort and fatigue for almost 1 month with a past history of chronic hepatitis B virus infection for 30 years. DIAGNOSIS: Based on the patient's performance status, tumor status assessed by computed tomography, liver function, he was diagnosed with HCC at BCLC stage C. INTERVENTIONS AND OUTCOMES: He first received transarterial chemoembolization (TACE) combined with sintilimab and lenvatinib as first-line treatment and experienced 10-month progression-free survival. After cancer progression, the patient participated in a clinical trial of ABSK-011, a novel fibroblast growth factor receptor 4 inhibitor, with a frustrating result. Then, the patient underwent TACE and received sintilimab plus lenvatinib again. Surprisingly, the tumor had a partial response, and the patient's serum alpha-fetoprotein returned to normal. LESSONS: The combined treatment of TACE plus systemic therapy might be an appropriate subsequent treatment.

Exploring the molecular mechanism of Epimedium for the treatment of ankylosing spondylitis based on network pharmacology, molecular docking, and molecular dynamics simulations.

Ankylosing spondylitis (AS) is a rheumatic disease that causes inflammation and bone formation in the spine. Despite significant advances in treatment, adverse side effects have triggered research into natural compounds. Epimedium (EP) is a traditional Chinese herb with a variety of pharmacological activities, including antirheumatic, anti-inflammatory, and immunomodulatory activities; however, its direct effects on AS treatment and the underlying molecular mechanisms have not been systematically studied. Thus, here, we used network pharmacology, molecular docking, and molecular dynamics simulations to explore the targets of EP for treating AS. We constructed an interaction network to elucidate the complex relationship between EP and AS. Sixteen active ingredients in EP were screened; 80 potential targets were identified. In particular, 8-(3-methylbut-2-enyl)-2-phenylchromone, anhydroicaritin, and luteolin were the core components and TNF, IL-6, IL-1ß, MMP9, and PTGS2 were the core targets. The GO and KEGG analyses indicated that EP may modulate multiple biological processes and pathways, including the AGE-RAGE, TNF, NF-κB/MAPK, and TLR signaling pathways, for AS treatment. Molecular docking and molecular dynamics simulations showed good affinity between the active components and core targets of EP, with stable binding within 100 nanoseconds. In particular, 8-(3-methylbut-2-enyl)-2-phenylchromone possessed the highest free energy of binding to PTGS2 and TNF (-115.575 and - 87.676 kcal/mol, respectively). Thus, EP may affect AS through multiple pathways, including the alleviation of inflammation, oxidative stress, and immune responses. In summary, we identified the active components and potential targets of EP, highlighting new strategies for the further experimental validation and exploration of lead compounds for treating AS.

JMJD6 Autoantibodies as a Potential Biomarker for Inflammation-Related Diseases.

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima-media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.

Quercetin promotes the proportion and maturation of NK cells by binding to MYH9 and improves cognitive functions in aged mice.

BACKGROUND: Quercetin is a flavonol compound widely distributed in plants that possesses diverse biological properties, including antioxidative, anti-inflammatory, anticancer, neuroprotective and senescent cell-clearing activities. It has been shown to effectively alleviate neurodegenerative diseases and enhance cognitive functions in various models. The immune system has been implicated in the regulation of brain function and cognitive abilities. However, it remains unclear whether quercetin enhances cognitive functions by interacting with the immune system. RESULTS: In this study, middle-aged female mice were administered quercetin via tail vein injection. Quercetin increased the proportion of NK cells, without affecting T or B cells, and improved cognitive performance. Depletion of NK cells significantly reduces cognitive ability in mice. RNA-seq analysis revealed that quercetin modulated the RNA profile of hippocampal tissues in aging animals towards a more youthful state. In vitro, quercetin significantly inhibited the differentiation of Lin-CD117+ hematopoietic stem cells into NK cells. Furthermore, quercetin promoted the proportion and maturation of NK cells by binding to the MYH9 protein. CONCLUSIONS: In summary, our findings suggest that quercetin promotes the proportion and maturation of NK cells by binding to the MYH9 protein, thereby improving cognitive performance in middle-aged mice.

Single-Cell Transcriptional Profile Construction of Rat Pituitary Glands before and after Sexual Maturation and Identification of Novel Marker Spp1 in Gonadotropes.

The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult pituitary gland tissues from different species or different sexes, and no research has yet resolved cellular differences in pituitary gland tissue before and after sexual maturation. Here, we identified a total of 15 cell clusters and constructed single-cell transcriptional profiles of rats before and after sexual maturation. Furthermore, focusing on the gonadotrope cluster, 106 genes were found to be differentially expressed before and after sexual maturation. It was verified that Spp1, which is specifically expressed in gonadotrope cells, could serve as a novel marker for this cell cluster and has a promotional effect on the synthesis and secretion of follicle-stimulating hormone. The results provide a new resource for further resolving the regulatory mechanism of pituitary gland development and pituitary hormone synthesis and secretion.

GnRH-driven FTO-mediated RNA m6A modification promotes gonadotropin synthesis and secretion.

BACKGROUND: Gonadotropin precisely controls mammalian reproductive activities. Systematic analysis of the mechanisms by which epigenetic modifications regulate the synthesis and secretion of gonadotropin can be useful for more precise regulation of the animal reproductive process. Previous studies have identified many differential m6A modifications in the GnRH-treated adenohypophysis. However, the molecular mechanism by which m6A modification regulates gonadotropin synthesis and secretion remains unclear. RESULTS: Herein, it was found that GnRH can promote gonadotropin synthesis and secretion by promoting the expression of FTO. Highly expressed FTO binds to Foxp2 mRNA in the nucleus, exerting a demethylation function and reducing m6A modification. After Foxp2 mRNA exits the nucleus, the lack of m6A modification prevents YTHDF3 from binding to it, resulting in increased stability and upregulation of Foxp2 mRNA expression, which activates the cAMP/PKA signaling pathway to promote gonadotropin synthesis and secretion. CONCLUSIONS: Overall, the study reveals the molecular mechanism of GnRH regulating the gonadotropin synthesis and secretion through FTO-mediated m6A modification. The results of this study allow systematic interpretation of the regulatory mechanism of gonadotropin synthesis and secretion in the pituitary at the epigenetic level and provide a theoretical basis for the application of reproductive hormones in the regulation of animal artificial reproduction.