Coronary microvascular dysfunction and myocardial area at risk assessed by cadmium zinc telluride single photon emission computed tomography after primary percutaneous coronary intervention in acute myocardial infarction patients.

Background: A high proportion of coronary microvascular dysfunction (CMD) has been observed in patients with acute myocardial infarction (AMI) who have received primary percutaneous coronary intervention (PCI), which may affect their prognosis. This study used cadmium zinc telluride (CZT) single photon emission computed tomography (SPECT) to evaluate the prevalence and characteristics of CMD and myocardial area at risk (AAR) in AMI patients who had undergone primary PCI. Methods: We conducted a single-center cross-sectional retrospective study at TEDA International Cardiovascular Hospital from September 2021 to June 2022. A total of 83 patients received primary PCI for AMI. Subsequently, a rest/stress dynamic and routine gated myocardial perfusion imaging (MPI) were performed 1 week after PCI. The CMD group was defined as having a residual stenosis of infarct-related artery (IRA) <50% and myocardial flow reserve (MFR) <2.0 in this corresponding territory, whereas MFR ≥2.0 of IRA pertained to the normal control group. Rest-AAR of infarction (%) and stress-AAR (%) were expressed by the percentage of measured rest-defect-size and stress-defect-size in the left ventricular area, respectively. Logistic regression analyses were performed to identify significant predictors of CMD. Results: A total of 53 patients with a mean age of 57.06±11.99 years were recruited, of whom 81.1% were ST-segment elevation myocardial infarction (STEMI). The proportion of patients with CMD was 79.2% (42/53). The time of pain to SPECT imaging was 7.50±1.27 days in the CMD group and 7.45±1.86 days among controls. CMD patients had a higher body mass index (BMI) than controls (26.48±3.26 vs. 24.36±2.73 kg/m2, P=0.053), and a higher proportion of STEMI, thrombolysis in myocardial infarction (TIMI) 0 grade of IRA prior PCI than controls (88.1% vs. 54.5%, P=0.011; 61.9% vs. 18.2%, P=0.004, respectively). No significant difference was identified in the rest-myocardial blood flow (MBF) of IRA between the 2 groups, whereas the stress-MBF and MFR of IRA, rest-AAR, and stress-AAR in the CMD group were remarkably lowered. Higher BMI [odds ratio (OR): 1.332, 95% confidence interval (CI): 1.008-1.760, P=0.044] and stress-AAR (OR: 1.994, 95% CI: 1.122-3.543, P=0.019) were used as independent predictors of CMD occurrence. Conclusions: The prevalence of CMD is high in AMI patients who received primary PCI. Each 1 kg/m2 increase in BMI was associated with a 1.3-fold increase in CMD risk. A 5% increase in stress-AAR was associated with a nearly 2-fold increase in CMD risk. Increased BMI and stress-AAR predicts decreased coronary reserve function.

Integration of Epigenome and Lactylome Reveals the Regulation of Lipid Production in Nannochloropsis oceanica.

Lysine lactylation (Kla) is a kind of novel post-translational modification (PTM) that participates in gene expression and various metabolic processes. Nannochloropsis has a remarkable capacity for triacylglycerol (TAG) production under nitrogen stress. To elucidate the involvement of lactylation in lipid synthesis, we conducted chromatin immunoprecipitation sequencing (ChIP-seq) and mRNA-seq analyses to monitor lactylation modifications and transcriptome alterations in Nannochloropsis oceanica. In all, 2057 genes showed considerable variation between nitrogen deprivation (ND) and nitrogen repletion (NR) conditions. Moreover, a total of 5375 differential Kla peaks were identified, including 5331 gain peaks and 44 loss peaks under ND vs NR. The differential Kla peaks were primarily distributed in the promoter (≤1 kb) (71.07%), 5'UTR (22.64%), and exon (4.25%). Integrative analysis of ChIP-seq, transcriptome, and previous proteome and lactylome data elucidates the potential mechanism by which lactylation promotes lipid accumulation under ND. Lactylation facilitates autophagy and protein degradation, leading to the recycling of carbon into the tricarboxylic acid (TCA) cycle, thereby providing carbon precursors for lipid synthesis. Additionally, lactylation induces the redirection of carbon from membrane lipids to TAG by upregulating lipases and enhancing the TCA cycle and ß-oxidation pathways. This research offers a new perspective for the investigation of lipid biosynthesis in Nannochloropsis.

Efficient removal of methyl orange and ciprofloxacin by reusable Eu-TiO2/PVDF membranes with adsorption and photocatalysis methods.

The presence of methyl orange (MO) and ciprofloxacin (CIP) in wastewater poses a serious threat to the environment and human health. Titanium dioxide nanoparticles (TiO2 NPs) are widely studied as photocatalysts for wastewater treatment. However, TiO2 NPs have the drawbacks of high energy required for activation, fast electron-hole pair recombination and difficulty in recovering from water. To overcome these problems, europium decorated titanium dioxide/poly(vinylidene fluoride) (Eu-TiO2/PVDF) membranes were successful prepared in this work by combining the modified sol-gel method and the immersion phase inversion method. The Eu-TiO2/PVDF membranes obtained with the increase of Eu-TiO2 NPs content during the preparation process were named M1, M2 and M3, respectively. The pure PVDF membrane without the addition of Eu-TiO2 NPs was named M0, which was prepared by the immersion phase inversion method and served as a reference. The prepared Eu-TiO2/PVDF membranes could not only adsorb MO, but also degrade CIP under visible-light irradiation. Moreover, the Eu-TiO2/PVDF membranes exhibited adsorption-photocatalytic activity towards a mixture of MO and CIP under visible-light irradiation. Last but not the least, the Eu-TiO2/PVDF membranes exhibited excellent recyclability and reusability, opening the avenue for a possible use of these membranes in sewage-treatment plants.

Effects of long-term intake of carotenoid-enriched eggs on healthy people: a randomized controlled study.

Red palm oil, a natural repository abundant in tocotrienols, tocopherols and carotenoids, is frequently employed as a pigment and nutritional enhancer in food products. The principal aim of this study is to explore the disparities in vitamin A levels, fatty acid profiles and gut microbiota among healthy adults who consume carotenoid-enriched eggs compared to those who consume normal eggs. A total of 200 hens were randomly assigned to either the red palm oil group or the soybean oil group, with the objective of producing carotenoid-enriched eggs and normal eggs. Throughout a six-month, double-blinded, randomized controlled trial, participants were instructed to consume one carotenoid-enriched or normal egg daily at a fixed time. Fecal and blood samples were collected from the participants at the start and conclusion of the six-month intervention period for further analysis. Our findings indicated that there was no significant change in the vitamin A level for daily supplementation with one carotenoid-enriched egg, but there were significant changes in some indicators of fatty acid profiles and gut microbiota compared to the control group of the population. Nonetheless, the consumption of eggs, regardless of carotenoid-enriched eggs or normal eggs, positively influenced dietary habits by reducing the intake of saturated fatty acids and enhancing the intake of monounsaturated and polyunsaturated fatty acids of the population.

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B.

BACKGROUND: LncRNAs regulate tumorigenesis and development in a variety of cancers. We substantiate for the first time that LINC00606 is considerably expressed in glioblastoma (GBM) patient specimens and is linked with adverse prognosis. This suggests that LINC00606 may have the potential to regulate glioma genesis and progression, and that the biological functions and molecular mechanisms of LINC00606 in GBM remain largely unknown. METHODS: The expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivo experiments. The molecular mechanism of LINC00606 was elucidated by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay. RESULTS: We demonstrated that LINC00606 promotes glioma cell proliferation, clonal expansion and migration, while reducing apoptosis levels. Mechanistically, on the one hand, LINC00606 can sponge miR-486-3p; the target gene TCF12 of miR-486-3p affects the transcriptional initiation of LINC00606, PTEN and KLLN. On the other hand, it can also regulate the PI3K/AKT signaling pathway to mediate glioma cell proliferation, migration and apoptosis by binding to ATP11B protein. CONCLUSIONS: Overall, the LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of GBM progression and plays a role in tumor regulation at transcriptional and post-transcriptional levels primarily through LINC00606 sponging miR-486-3p and targeted binding to ATP11B. Therefore, our research on the regulatory network LINC00606 could be a novel therapeutic strategy for the treatment of GBM.

Enhancing antitumor efficacy of NIR-I region zinc phthalocyanine@upconversion nanoparticle through lysosomal escape and mitochondria targeting.

Accurately visualizing the intracellular trafficking of upconversion nanoparticles (UCNPs) loaded with phthalocyanines and achieving precise photodynamic therapy (PDT) using near-infrared (NIR) laser irradiation still present challenges. In this study, a novel NIR laser-triggered upconversion luminescence (UCL) imaging-guided nanoparticle called FA@TPA-NH-ZnPc@UCNPs (FTU) was developed for PDT. FTU consisted of UCNPs, folic acid (FA), and triphenylamino-phenylaniline zinc phthalocyanine (TPA-NH-ZnPc). Notably, TPA-NH-ZnPc showcases aggregation-induced emission (AIE) characteristic and NIR absorption properties at 741 nm, synthesized initially via molybdenum-catalyzed condensation reaction. The UCL emitted by FTU enable real-time visualization of their subcellular localization and intracellular trafficking within ovarian cancer HO-8910 cells. Fluorescence images revealed that FTU managed to escape from lysosomes due to the "proton sponge" effect of TPA-NH-ZnPc. The FA ligands on the surface of FTU further directed their transport and accumulation within mitochondria. When excited by a 980 nm laser, FTU exhibited UCL and activated TPA-NH-ZnPc, consequently generating cytotoxic singlet oxygen (1O2), disrupted mitochondrial function and induced apoptosis in cancer cells, which demonstrated great potential for tumor ablation.

Supramolecular interaction between berberine hydrochloride and baicalin in aqueous solution: Reaction kinetics, spectral analysis and dynamic simulation.

The current study presents a comprehensive investigation on the precipitation reaction and supramolecular interactions between berberine hydrochloride (BBR) and baicalin (BA) in an aqueous system. Utilizing a combination of multi-spectral analytical techniques and molecular dynamic simulations, we elucidated the mechanism of the complexion process. The precipitate formation was observed within a drug concentration range of 0.1-1.0 mM, and a 1:1 stoichiometry ratio of BBR to BA was established by the Job's plot method. Morphological and structural characterizations of the precipitates were conducted using DSC, FTIR and PXRD. Additionally, UV-Vis absorption and 1H NMR spectroscopy were employed to compare the spectral characteristics of the precipitates with those of individual drug solution. Molecular dynamic simulations further dissected the intermolecular interactions and self-assembly mechanisms. The precipitates formed were amorphous microparticles with an average diameter of approximately 20 µm, primarily stabilized by hydrogen bonding and π-π stacking. This study contributes foundational insights into the supramolecular interactions between BBR and BA, therefore facilitated a better understanding of the precipitation process involving flavonoid-alkaloid pairs in mixed aqueous solutions.

Senolytic combination of dasatinib and quercetin attenuates renal damage in diabetic kidney disease.

BACKGROUND: Senolytic combination of dasatinib and quercetin (DQ) is the most studied senolytics drugs used to treat various age-related diseases. However, its protective activity against diabetic kidney disease (DKD) and underlying mechanisms are uncertain. PURPOSE: To investigate the functions and potential mechanisms of the senolytics DQ on DKD. METHODS: Diabetic db/db mice were administrated DQ or transfected with over-expressed PPARα or shPPARα vector. The positive control group was administered irbesartan. Renal function and fibrotic changes in kidney tissue were tested. Single-cell RNA-seq (scRNA-seq) was conducted to analyze the differential transcriptome between the diabetic and control mice. Molecular docking simulation was used to assess the combination of DQ and potential factors. Moreover, tubular epithelial cells under high-glucose (HG) conditions were incubated with DQ and transfected with or without over-expressed PPARα/siPPARα vector. RESULTS: DQ significantly improved renal function, histopathological and fibrotic changes, alleviated lipid deposition, and increased ATP levels in mice with DKD. DQ reduced multiple fatty acid oxidation (FAO) pathway-related proteins and up-regulated PPARα in db/db mice. Overexpression of PPARα upregulated the expression of PPARα-targeting downstream FAO pathway-related proteins, restored renal function, and inhibited renal fibrosis in vitro and in vivo. Moreover, molecular docking and dynamics simulation analyses indicated the nephroprotective effect of DQ via binding to PPARα. Knockdown of PPARα reversed the effect of DQ on the FAO pathway and impaired the protective effect of DQ during DKD. CONCLUSION: For the first time, DQ was found to exert a renal protective effect by binding to PPARα and attenuating renal damage through the promotion of FAO in DKD.

Synchronously Sensitive Immunoassay and Efficient Inactivation of Living Zika Virus via DNAzyme Catalytic Amplification and In Situ Aggregation-Induced Emission Photosensitizer Generation.

Sensitive identification and effective inactivation of the virus are paramount for the early diagnosis and treatment of viral infections to prevent the risk of secondary transmission of viruses in the environment. Herein, we developed a novel two-step fluorescence immunoassay using antibody/streptavidin dual-labeled polystyrene nanobeads and biotin-labeled G-quadruplex/hemin DNAzymes with peroxidase-mimicking activity for sensitive quantitation and efficient inactivation of living Zika virus (ZIKV). The dual-labeled nanobeads can specifically bind ZIKV through E protein targeting and simultaneously accumulate DNAzymes, leading to the catalytic oxidation of Amplex Red indicators and generation of intensified aggregation-induced emission fluorescence signals, with a detection limit down to 66.3 PFU/mL and 100% accuracy. Furthermore, robust reactive oxygen species generated in situ by oxidized Amplex Red upon irradiation can completely kill the virus. This sensitive and efficient detection-inactivation integrated system will expand the viral diagnostic tools and reduce the risk of virus transmission in the environment.

Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production.

Psoriasis is a common chronic inflammatory skin disease driven by the aberrant activation of dendritic cells (DCs) and T cells, ultimately leading to increased production of cytokines such as interleukin (IL)-23 and IL-17A. It is established that the cGAS-STING pathway is essential for psoriatic inflammation, however, the specific role of cGAS-STING signaling in DCs within this context remains unclear. In this study, we demonstrated the upregulation of cGAS-STING signaling in psoriatic lesions by analyzing samples from both clinical patients and imiquimod (IMQ)-treated mice. Using a conditional Sting-knockout transgenic mouse model, we elucidated the impact of cGAS-STING signaling in DCs on the activation of IL-17- and IFN-γ-producing T cells in psoriatic inflammation. Ablation of the Sting hampers DC activation leads to decreased numbers of IL-17-producing T cells and Th1 cells, and thus subsequently attenuates psoriatic inflammation in the IMQ-induced mouse model. Furthermore, we explored the therapeutic potential of the STING inhibitor C-176, which reduces psoriatic inflammation and enhances the anti-IL-17A therapeutic response. Our results underscore the critical role of cGAS-STING signaling in DCs in driving psoriatic inflammation and highlight a promising psoriasis treatment.

Activation of Pink1/Parkin-mediated mitochondrial autophagy alleviates exertional heat stroke-induced acute lung injury in rats.

OBJECTIVE: To investigate the role of Pink1/Parkin-mediated mitochondrial autophagy in exertional heat stroke-induced acute lung injury in rats. METHODS: Sixty SD rats were divided into four groups: normal group (CON group), normal Parkin overexpression group (CON + Parkin group), exertional heat stroke group (EHS group), and exertional heat stroke Parkin overexpression group (EHS + Parkin group). Adeno-associated virus carrying the Parkin gene was intravenously injected into the rats to overexpress Parkin in the lung tissue. An exertional heat stroke rat model was established, and survival curves were plotted. Lung micro-CT was performed, and lung coefficient and pulmonary microvascular permeability were measured. RESULTS: Compared with the EHS group, the survival rate of rats in the EHS + Parkin overexpression group was significantly increased, lung coefficient and pulmonary microvascular permeability were reduced, and pathological changes such as exudation and consolidation were significantly reduced. The levels of inflammatory factors IL-6, IL-1ß, TNF- α, and ROS were significantly decreased; the degree of mitochondrial swelling in type II alveolar epithelial cells was reduced, and no vacuolization was observed. Lung tissue apoptosis was reduced, and the colocalization fluorescence of Pink1 and Parkin, as well as LC3 and Tom20, were increased. The expression of Parkin and LC3-II/LC3-I ratio in lung tissue were both increased, while the expression of P62, Pink1, MFN2, and PTEN-L was decreased. CONCLUSION: Impairment of Pink1/Parkin-mediated mitochondrial autophagy function is one of the mechanisms of exertional heat stroke-induced acute lung injury in rats. Activation of the Pink1/Parkin pathway can alleviate acute lung injury caused by exertional heat stroke.

Influenza A virus infection disrupts the function of syncytiotrophoblast cells and contributes to adverse pregnancy outcomes.

Pregnancy heightens susceptibility to influenza A virus (IAV) infection, thereby increasing the risk of severe pneumonia and maternal mortality. It also raises the chances of adverse outcomes in offspring, such as fetal growth restriction, preterm birth, miscarriage, and stillbirth in offsprings. However, the underlying mechanisms behind these effects remain largely unknown. Syncytiotrophoblast cells, crucial in forming the placental barrier, nutrient exchange and hormone secretion, have not been extensively studied for their responses to IAV. In our experiment, we used Forskolin-treated BeWo cells to mimic syncytiotrophoblast cells in vitro, and infected them with H1N1, H5N1 and H7N9 virus stains. Our results showed that syncytiotrophoblast cells, with their higher intensity of sialic acid receptors, strongly support IAV infection and replication. Notably, high-dose viral infection and prolonged exposure resulted in a significant decrease in fusion index, as well as gene and protein expression levels associated with trophoblast differentiation, ß-human chorionic gonadotropin secretion, estrogen and progesterone biosynthesis, and nutrient transport. In pregnant BALB/c mice infected with the H1N1 virus, we observed significant decreases in trophoblast differentiation and hormone secretion gene expression levels. IAV infection also resulted in preterm labor, fetal growth restriction, and increased maternal and fetal morbidity and mortality. Our findings indicate that IAV infection in syncytiotrophoblastic cells can result in adverse pregnancy outcomes by altering trophoblast differentiation, suppressing of ß-hCG secretion, and disrupting placental barrier function.

Persimmon leaf polyphenols as potential ingredients for modulating starch digestibility: Effect of starch-polyphenol interaction.

The interaction mode between persimmon leaf polyphenols (PLP) and corn starch with different amylose content and its effect on starch digestibility was studied. Results of iodine binding test, TGA, and DSC revealed that PLP interacted with starch and reduced the iodine binding capacity and thermal stability of starch. High amylopectin corn starch (HAPS) interacted with PLP mainly via hydrogen bonds, since the FT-IR of HAPS-PLP complex showed higher intensity at 3400 cm-1 and an obvious shift of 21 cm-1 to shorter wavelength, and the chemical shifts of protons in 1H NMR and the shift of C-6 peak in 13C NMR of HAPS moved to low field with the addition of PLP. Results of 1H NMR also showed the preferential formation of hydrogen bonds between PLP and OH-3 of HAPS. Different from HAPS, PLP formed V-type inclusion complex with high amylose corn starch (HAS) because XRD of HAS-PLP complex showed characteristic feature peaks of V-type inclusion complex and C-1 signal in 13C NMR of PLP-complexed HAS shifted to low field. Interaction with PLP reduced starch digestibility and HAS-PLP complex resulted in more resistant starch production than HAPS-PLP complex. To complex PLP with starch might be a potential way to prepare functional starch with slower digestion.

Cytochrome GmGLY1 is Involved in the Biosynthesis of Glycitein in Soybean.

Isoflavones, the major secondary metabolites of interest due to their benefits to both human and plant health, are exclusively produced by legumes. In this study, we profiled the isoflavone content in dry seeds from 211 soybean [Glycine max (L.) Merr.] accessions grown across five environments. Broad and discernible phenotypic variations were observed among accessions, regions, and years of growth. Twenty-six single-nucleotide polymorphisms (SNPs) associated with the sum of glycitein (GLE), glycitin (GL), 6″-O-acetylglycitin (AGL), and 6″-O-malonylglycitin (MGL) contents were detected in multiple environments via a genome-wide association study (GWAS). These SNPs were located on chromosome 11 (8,148,438 bp to 8,296,956 bp, renamed qGly11-01). Glyma.11g108300 (GmGLY1), a gene that encodes a P450 family protein, was identified via sequence variation analysis, functional annotation, weighted gene coexpression network analysis (WGCNA), and expression profile analysis of candidate gene, and hairy roots transformation in soybean. Overexpression of GmGLY1 increased the glycitein content (GLC) in soybean hairy roots and transgenic seeds, while CRISPR/Cas9-generated mutants exhibited decreased GLC and increased daidzein content (DAC). Haplotype analysis revealed that GmGLY1 allelic variations significantly affect the GLC accumulation. These findings enhance our understanding of genes influencing GLC in soybean and may guide breeding for lines with high and stable GLC.

Increased Cerebral Level of P2X7R in a Tauopathy Mouse Model by PET Using [18F]GSK1482160.

Neuroinflammation plays an important role in Alzheimer's disease and primary tauopathies. The aim of the current study was to map [18F]GSK1482160 for imaging of purinergic P2X7R in Alzheimer's disease and primary tauopathy mouse models. Small animal PET was performed using [18F]GSK1482160 in widely used mouse models of Alzheimer's disease (APP/PS1, 5×FAD, and 3×Tg), 4-repeat tauopathy (rTg4510) mice, and age-matched wild-type mice. Increased uptake of [18F]GSK1482160 was observed in the brains of 7-month-old rTg4510 mice compared to wild-type mice and compared to 3-month-old rTg4510 mice. A positive correlation between hippocampal tau [18F]APN-1607 and [18F]GSK1482160 uptake was found in rTg4510 mice. No significant differences in the uptake of [18F]GSK1482160 was observed for APP/PS1 mice, 5×FAD mice, or 3×Tg mice. Immunofluorescence staining further indicated the distribution of P2X7Rs in the brains of 7-month-old rTg4510 mice with accumulation of tau inclusion. These findings provide in vivo imaging evidence for an increased level of P2X7R in the brains of tauopathy mice.

Association of past and current sleep duration with structural brain differences: A large population-based study from the UK Biobank.

OBJECTIVE: This study aimed to examine the association between past/current sleep duration and macro-/micro-structural brain outcomes and explore whether hypertension or social activity plays a role in such association. METHODS: Within the UK Biobank, 40 436 dementia-free participants (age 40-70 years) underwent a baseline assessment followed by a brain magnetic resonance imaging (MRI) scan 9 years later. Past (baseline) and current (MRI scans) sleep duration (hours/day) were recorded and classified as short (≤5), intermediate (6-8), and long (≥9). Brain structural volumes and diffusion markers were assessed by MRI scans. RESULTS: Compared with past intermediate sleep, past short sleep was related to smaller cortex volumes (standardized ß [95 % CI]: -0.04 [-0.07, -0.02]) and lower regional fractional anisotropy (FA) (-0.08 [-0.13, -0.03]), while past long sleep was related to smaller regional subcortical volumes (standardized ß: -0.04 to -0.07 for thalamus, accumbens, and hippocampus). Compared to current intermediate sleep, current short sleep was associated with smaller cortex volumes (-0.03 [-0.05, -0.01]), greater white matter hyperintensities (WMH) volumes (0.04 [0.01, 0.08]), and lower regional FA (-0.07 [-0.11, -0.02]). However, current long sleep was related to smaller total brain (-0.03 [-0.05, -0.02]), grey matter (-0.05 [-0.07, -0.03]), cortex (-0.05 [-0.07, -0.03]), regional subcortical volumes [standardized ß: -0.05 to -0.09 for putamen, thalamus, hippocampus, and accumbens]), greater WMH volumes (0.06 [0.03, 0.09]), as well as lower regional FA (-0.05 [-0.09, -0.02]). The association between current long sleep duration and poor brain health was stronger among people with hypertension or low frequency of social activity (all Pinteraction <0.05). CONCLUSIONS: Both past and current short/long sleep are associated with smaller brain volume and poorer white matter health in the brain, especially in individuals with hypertension and low frequency of social activity. Our findings highlight the need to maintain 6-8 h' sleep duration for healthy brain aging.

17ß-estradiol Inhibits Oxidative Stress-Induced Apoptosis in Endometrial Cancer Cells by Promoting FOXM1 Expression.

The steroid hormone 17ß-estradiol (E2) has a significant impact on the development and progression of tumors. E2 stimulates tumor cell growth and metabolism, leading to an increase in reactive oxygen species (ROS) production. However, the rise in ROS levels is not sufficient to cause severe harm to cancer cells. and the mechanisms that regulate ROS are not well understood. Since FOXM1 plays a crucial role in the production of ROS, we aimed to investigate the impact of E2 on oxidative stress and the involvement of FOXM1 in the Ishikawa endometrial cancer cell line. Our research revealed that E2 controls the levels of ROS inside cells and safeguards them from apoptosis by promoting the expression of FOXM1. We observed a decrease in the expression of FOXM1 alongside an increase in oxidative damage. Moreover, cells demonstrated elevated levels of FOXM1 and ERα upon E2 treatment. Overall, our findings suggest that E2 prevents apoptosis induced by oxidative stress in endometrial cancer cells by encouraging the expression of FOXM1, potentially affecting ERα.

Predicting the Efficacy of Repeated Shockwave Lithotripsy for Treating Patients with Upper Urinary Tract Calculi Using an Artificial Neural Network Model.

PURPOSE: To establish a prediction model for repeated shockwave lithotripsy (SWL) efficacy to help choose an appropriate treatment plan for patients with a single failed lithotripsy, reducing their treatment burden. PATIENTS AND METHODS: The clinical records and imaging data of 304 patients who underwent repeat SWL for upper urinary tract calculi (UUTC) at the Urology Centre of Shiyan People's Hospital between April 2019 and April 2023 were retrospectively collected. This dataset was divided into training (N = 217; 146 males [67.3%] and 71 females [32.7%]) and validation (N = 87; 66 males [75.9%] and 21 females [24.1%]) sets. The overall predictive accuracy of the models was calculated separately for the training and validation.  Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC) was calculated. The normalized importance of each independent variable (derived from the one-way analyses) in the input layer of the artificial neural network (ANN) model for the dependent variable (success or failure in repeat SWL) in the output layer was plotted as a bar chart. RESULTS: This study included 304 patients, of whom 154 (50.7%) underwent successful repeat SWL. Predictive models were constructed in the training set and assessed in the validation set. Fourteen influencing factors were selected as input variables to build an ANN model: age, alcohol, body mass index, sex, hydronephrosis, hematuria, mean stone density (MSD), skin-to-stone distance (SSD), stone heterogeneity index (SHI), stone volume (SV), stone retention time, smoking, stone location, and urinary irritation symptom. The model's AUC was 0.852 (95% confidence interval (CI): 0.8-0.9), and its predictive accuracy for stone clearance in the validation group was 83.3%. The order of importance of the independent variables was MSD > SV > SSD > stone retention time > SHI. CONCLUSION: Establishing an ANN model for repeated SWL of UUTC is crucial for optimizing patient care. This model will be pivotal in providing accurate treatment plans for patients with an initial unsuccessful SWL treatment. Moreover, it can significantly enhance the success rate of subsequent SWL treatments, ultimately alleviating patients' treatment burden.

Isolation and identification of a novel phage targeting clinical multidrug-resistant Corynebacterium striatum isolates.

Introduction: Over the past decade, Corynebacterium striatum (C. striatum), an emerging multidrug-resistant (MDR) pathogen, has significantly challenged healthcare settings, especially those involving individuals with weakened immune systems. The rise of these superbugs necessitates innovative solutions. Methods: This study aimed to isolate and characterize bacteriophages targeting MDR-C. striatum. Utilizing 54 MDR-C. striatum isolates from a local hospital as target strains, samples were collected from restroom puddles for phage screening. Dot Plaque and Double-layer plate Assays were employed for screening. Results: A novel temperate bacteriophage, named CSP1, was identified through a series of procedures, including purification, genome extraction, sequencing, and one-step growth curves. CSP1 possesses a 39,752 base pair circular double-stranded DNA genome with HK97-like structural proteins and potential for site-specific recombination. It represents a new species within the unclassified Caudoviricetes class, as supported by transmission electron microscopy, genomic evolutionary analysis, and collinearity studies. Notably, CSP1 infected and lysed 21 clinical MDR-C. striatum isolates, demonstrating a wide host range. The phage remained stable in conditions ranging from -40 to 55°C, pH 4 to 12, and in 0.9% NaCl buffer, showing no cytotoxicity. Discussion: The identification of CSP1 as the first phage targeting clinical C. striatum strains opens new possibilities in bacteriophage therapy research, and the development of diagnostic and therapeutic tools against pathogenic bacteria.