NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal, and aging-associated interstitial lung disease with a poor prognosis and limited treatment options, while the pathogenesis remains elusive. In this study, we found that the expression of nuclear receptor subfamily 2 group F member 2 (NR2F2), a member of the steroid thyroid hormone superfamily of nuclear receptors, was reduced in both IPF and bleomycin-induced fibrotic lungs, markedly in bleomycin-induced senescent epithelial cells. Inhibition of NR2F2 expression increased the expression of senescence markers such as p21 and p16 in lung epithelial cells, and activated fibroblasts through epithelial-mesenchymal crosstalk, inversely overexpression of NR2F2 alleviated bleomycin-induced epithelial cell senescence and inhibited fibroblast activation. Subsequent mechanistic studies revealed that overexpression of NR2F2 alleviated DNA damage in lung epithelial cells and inhibited cell senescence. Adenovirus-mediated Nr2f2 overexpression attenuated bleomycin-induced lung fibrosis and cell senescence in mice. In summary, these data demonstrate that NR2F2 is involved in lung epithelial cell senescence, and targeting NR2F2 may be a promising therapeutic approach against lung cell senescence and fibrosis.

Ticagrelor vs clopidogrel when coadministered with bivalirudin in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Background: The optimal perioperative antithrombotic strategy for patients with acute coronary syndrome (ACS) during percutaneous coronary intervention (PCI) remains controversial. Objectives: To determine the safety and effectiveness of bivalirudin plus ticagrelor vs bivalirudin plus clopidogrel in patients with ACS undergoing PCI in the real world. Methods: Between March 2016 and March 2019, 7234 patients with ACS who had undergone PCI, received bivalirudin periprocedurally, and were prescribed ticagrelor or clopidogrel were enrolled in a single-center, all-comer, modern, retrospective cohort study. Incidence rates of 12-month ischemia (cardiac death, myocardial infarction, or stroke), all-cause death, Bleeding Academic Research Consortium (BARC) type 2,3,5 bleeding, and BARC type 3,5 bleeding were compared between different groups. Results: In total, 4960 patients received bivalirudin plus clopidogrel and 2274 patients received bivalirudin plus ticagrelor. Compared with bivalirudin plus clopidogrel, bivalirudin plus ticagrelor was associated with lower ischemic events (1.74% vs 2.84%; relative risk, 0.61; 95% CI, 0.41-0.91; P = .02) and stroke (0.05% vs 1.01%, P < .001) within 12 months after PCI without excessive risk of bleeding (BARC type 2,3,5 bleeding: 4.49% vs 3.76%, P = .22; BARC type 3,5 bleeding: 2.84% vs 2.02%, P = .08). The beneficial effects of bivalirudin plus ticagrelor were consistent among subgroups. Conclusion: As an initial treatment strategy, bivalirudin plus ticagrelor could reduce the 12-month risk of ischemic events compared with bivalirudin plus clopidogrel significantly without increasing the bleeding risk in ACS patients undergoing PCI.

A progress update on the biological effects of biodegradable microplastics on soil and ocean environment: a perfect substitute or new threat?

Conventional plastics are inherently difficult to degrade, causing serious plastic pollution. With the development of society, biodegradable plastics (BPs) are considered as an alternative to traditional plastics. However, current research indicated that BPs do not undergo complete degradation in natural environments. Instead, they may convert into biodegradable microplastics (BMPs) at an accelerated rate, thereby posing a significant threat to environment. In this paper, the definition, application, distribution, degradation behaviors, bioaccumulation and biomagnification of BPs were reviewed. And the impacts of BMPs on soil and marine ecosystems, in terms of physicochemical property, nutrient cycling, microorganisms, plants and animals were comprehensively summarized. The effects of combined exposure of BMPs with other pollutants, and the mechanism of ecotoxicity induced by BMPs were also addressed. It was found that BMPs reduced pH, increased DOC content, and disrupted the nitrification of nitrogen cycle in soil ecosystem. The shoot dry weight, pod number and root growth of soil plants, and reproduction and body length of soil animals were inhibited by BMPs. Furthermore, the growth of marine plant, and locomotion, body length and survival of marine animals were suppressed by BMPs. Additionally, the ecotoxicity of combined exposure of BMPs with other pollutants has not been uniformly concluded. Exposure to BMPs induced several types of toxicity, including neurotoxicity, gastrointestinal toxicity, reproductive toxicity, immunotoxicity and genotoxicity. The future calls for heightened attention towards the regulation of the degradation of BPs in the environment, and pursuit of interventions aimed at mitigating their ecotoxicity and potential health risks to human.

Lymph node dissection in small-sized pulmonary metastasectomy: Impact on the long-term survival.

INTRODUCTION: Pulmonary metastasectomy has been clarified in improving long-term survival in most primary malignancies with pulmonary metastasis, while the role of additional lymph node dissection remained controversial. We aimed to investigate the prognosis of lymph node involvement and identify the role of lymph node dissection during pulmonary metastasectomy in a real-world cohort. METHODS: We identified patients diagnosed with pulmonary metastases with ≤3 cm in size and received pulmonary metastasectomy between 2004 and 2017 in the Surveillance, Epidemiology, and End Results database. We compared the survival via Kaplan-Meier analysis and propensity score matching method, and the multivariable analysis was conducted by cox regression analysis. RESULTS: A total of 3452 patients were included, of which 2268(65.7%) received lymph node dissection, and the incidence of node-positive was 11.3%(256/2268). In total, the median overall survival was 62.8 months(interquartile range, 28.6-118.9 months), and the lymph node involvement was referred to an impaired survival compared to node-negative diseases(5-year overall survival rate, 58.0% versus 38.6%), with comparable survival between N1 and N2 diseases(P = 0.774). Lymph node dissection was associated with improved survival(HR = 0.80; 95%CI, 0.71-0.90; P < 0.001), and the survival benefits remained regardless of age, sex, the number of metastases, and surgical procedures, even in those with node-negative diseases. At least eight LNDs might lead to a significant improvement in survival, and additional survival benefits might be limited with additional dissected lymph nodes. CONCLUSIONS: Lymph node involvement was associated with impaired survival, and lymph node dissection during pulmonary metastasectomy could improve long-term survival and more accurate staging.

Single-cell transcriptomics in MI identify Slc25a4 as a new modulator of mitochondrial malfunction and apoptosis-associated cardiomyocyte subcluster.

Myocardial infarction (MI) is the leading cause of premature death. The death of cardiomyocytes (CMs) and the dysfunction of the remaining viable CMs are the main pathological factors contributing to heart failure (HF) following MI. This study aims to determine the transcriptional profile of CMs and investigate the heterogeneity among CMs under hypoxic conditions. Single-cell atlases of the heart in both the sham and MI groups were developed using single-cell data (GSE214611) downloaded from Gene Expression Omnibus (GEO) database ( https://www.ncbi.nlm.nih.gov/geo/ ). The heterogeneity among CMs was explored through various analyses including enrichment, pseudo time, and intercellular communication analysis. The marker gene of C5 was identified using differential expression analysis (DEA). Real-time polymerase chain reaction (RT-PCR), bulk RNA-sequencing dataset analysis, western blotting, immunohistochemical and immunofluorescence staining, Mito-Tracker staining, TUNEL staining, and flow cytometry analysis were conducted to validate the impact of the marker gene on mitochondrial function and cell apoptosis of CMs under hypoxic conditions. We identified a cell subcluster named C5 that exhibited a close association with mitochondrial malfunction and cellular apoptosis characteristics, and identified Slc25a4 as a significant biomarker of C5. Furthermore, our findings indicated that the expression of Slc25a4 was increased in failing hearts, and the downregulation of Slc25a4 improved mitochondrial function and reduced cell apoptosis. Our study significantly identified a distinct subcluster of CMs that exhibited strong associations with ventricular remodeling following MI. Slc25a4 served as the hub gene for C5, highlighting its significant potential as a novel therapeutic target for MI.

Exosomal miR-1202 mediates Brodmann Area 44 functional connectivity changes in medication-free patients with major depressive disorder: An fMRI study.

Previous large-sample postmortem study revealed that the expression of miR-1202 in brain tissues from Brodmann area 44 (BA44) was dysregulated in patients with major depressive disorder (MDDs). However, the specific in vivo neuropathological mechanism of miR-1202 as well as its interplay with BA44 circuits in the depressed brain are still unclear. Here, we performed a case-control study with imaging-genetic approach based on resting-state functional magnetic resonance imaging (MRI) data and miR-1202 quantification from 110 medication-free MDDs and 102 healthy controls. Serum-derived circulating exosomes that readily cross the blood-brain barrier were isolated to quantify miR-1202. For validation, repeated MR scans were performed after a six-week follow-up of antidepressant treatment on a cohort of MDDs. Voxelwise factorial analysis revealed two brain areas (including the striatal-thalamic region) in which the effect of depression on the functional connectivity with BA44 was significantly dependent on the expression level of exosomal miR-1202. Moreover, longitudinal change of the BA44 connectivity with the striatal-thalamic region in MDDs after antidepressant treatment was found to be significantly related to the level of miR-1202 expression. These findings revealed that the in vivo neuropathological effect of miR-1202 dysregulation in depression is possibly exerted by mediating neural functional abnormalities in BA44-striatal-thalamic circuits.

ß cell acetate production and release are negligible.

BACKGROUND: Studies suggest that short chain fatty acids (SCFAs), which are primarily produced from fermentation of fiber, regulate insulin secretion through free fatty acid receptors 2 and 3 (FFA2 and FFA3). As these are G-protein coupled receptors (GPCRs), they have potential therapeutic value as targets for treating type 2 diabetes (T2D). The exact mechanism by which these receptors regulate insulin secretion and other aspects of pancreatic ß cell function is unclear. It has been reported that glucose-dependent release of acetate from pancreatic ß cells negatively regulates glucose stimulated insulin secretion. While these data raise the possibility of acetate's potential autocrine action on these receptors, these findings have not been independently confirmed, and multiple concerns exist with this observation, particularly the lack of specificity and precision of the acetate detection methodology used. METHODS: Using Min6 cells and mouse islets, we assessed acetate and pyruvate production and secretion in response to different glucose concentrations, via liquid chromatography mass spectrometry. RESULTS: Using Min6 cells and mouse islets, we showed that both intracellular pyruvate and acetate increased with high glucose conditions; however, intracellular acetate level increased only slightly and exclusively in Min6 cells but not in the islets. Further, extracellular acetate levels were not affected by the concentration of glucose in the incubation medium of either Min6 cells or islets. CONCLUSIONS: Our findings do not substantiate the glucose-dependent release of acetate from pancreatic ß cells, and therefore, invalidate the possibility of an autocrine inhibitory effect on glucose stimulated insulin secretion.

Novel Ag3PO4/ZnWO4-modified graphite felt electrode for photoelectrocatalytic removal of harmful algae: Performance and mechanism.

A novel Ag3PO4/ZnWO4-modified graphite felt electrode (AZW@GF) was prepared by drop coating method and applied to photoelectrocatalytic removal of harmful algae. Results showed that approximately 99.21% of chlorophyll a and 91.57% of Microcystin-LR (MCLR) were degraded by the AZW@GF-Pt photoelectrocatalytic system under the optimal operating conditions with a rate constant of 0.02617 min-1 and 0.01416 min-1, respectively. The calculated synergistic coefficient of photoelectrocatalytic algal removal and MC-LR degradation by the AZW@GF-Pt system was both larger than 1.9. In addition, the experiments of quenching experiments and electron spin resonance (ESR) revealed that the photoelectrocatalytic reaction mainly generated •OH and •O2- for algal removal and MC-LR degradation. Furthermore, the potential pathway for photoelectrocatalytic degradation of MC-LR was proposed. Finally, the photoelectrocatalytic cycle algae removal experiments were carried out on AZW@GF electrode, which was found to maintain the algae removal efficiency at about 91% after three cycles of use, indicating that the photoelectrocatalysis of AZW@GF electrode is an effective emergency algae removal technology.

Heat's Role in Solution Electrospinning: A Novel Approach to Nanofiber Structure Optimization.

In this study, we explored an innovative application of heat-assisted solution electrospinning, a technique that significantly advances the control of phase separation in polystyrene (PS) fibers. Our experimental approach involved the use of direct heating and a convection air sheath applied through a coaxial needle, focusing on solvents with varying vapor pressures. This method enabled a detailed investigation into how solvent evaporation rates affect the morphology of the electrospun fibers. SEM and AFM measurements revealed that the application of direct heating and a heated air sheath offered precise control over the fiber morphology, significantly influencing both the surface and internal structure of the fibers. Additionally, we observed notable changes in fiber diameter, indicating that heat-assisted electrospinning can be effectively utilized to tailor fiber dimensions according to specific application requirements. Moreover, our research demonstrated the critical role of solvent properties, particularly vapor pressure, in determining the final characteristics of the electrospun fibers. By comparing fibers produced with different solvents, we gained insights into the complex interplay between solvent dynamics and heat application in fiber formation. The implications of these findings are far-reaching, offering new possibilities for the fabrication of nanofibers with customized properties. Furthermore, this could have profound impacts on various applications, from biomedical to environmental, where specific fiber characteristics are crucial. This study not only contributes to the understanding of phase separation in electrospinning but also opens avenues for further research on the optimization of fiber properties for diverse industrial and scientific applications.

Small regulatory RNA RSaX28 promotes virulence by reinforcing the stability of RNAIII in community-associated ST398 clonotype Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a notorious pathogen that cause metastatic or complicated infections. Hypervirulent ST398 clonotype strains, remarkably increased in recent years, dominated Community-associated S. aureus (CA-SA) infections in the past decade in China. Small RNAs like RNAIII have been demonstrated to play important roles in regulating the virulence of S. aureus, however, the regulatory roles played by many of these sRNAs in the ST398 clonotype strains are still unclear. Through transcriptome screening and combined with knockout phenotype analysis, we have identified a highly transcribed sRNA, RSaX28, in the ST398 clonotype strains. Sequence analysis revealed that RSaX28 is highly conserved in the most epidemic clonotypes of S. aureus, but its high transcription level is particularly prominent in the ST398 clonotype strains. Characterization of RSaX28 through RACE and Northern blot revealed its length to be 533nt. RSaX28 is capable of promoting the hemolytic ability, reducing biofilm formation capacity, and enhancing virulence of S. aureus in the in vivo murine infection model. Through IntaRNA prediction and EMSA validation, we found that RSaX28 can specifically interact with RNAIII, promoting its stability and positively regulating the translation of downstream alpha-toxin while inhibiting the translation of Sbi, thereby regulating the virulence and biofilm formation capacity of the ST398 clonotype strains. RSaX28 is an important virulence regulatory factor in the ST398 clonotype S. aureus and represents a potential important target for future treatment and immune intervention against S. aureus infections.

A nomogram model for predicting intramyocardial hemorrhage post-PCI based on SYNTAX score and clinical features.

OBJECTIVE: The aim of this study is to develop a nomogram model for predicting the occurrence of intramyocardial hemorrhage (IMH) in patients with Acute Myocardial Infarction (AMI) following Percutaneous Coronary Intervention (PCI). The model is constructed utilizing clinical data and the SYNTAX Score (SS), and its predictive value is thoroughly evaluated. METHODS: A retrospective study was conducted, including 216 patients with AMI who underwent Cardiac Magnetic Resonance (CMR) within a week post-PCI. Clinical data were collected for all patients, and their SS were calculated based on coronary angiography results. Based on the presence or absence of IMH as indicated by CMR, patients were categorized into two groups: the IMH group (109 patients) and the non-IMH group (107 patients). The patients were randomly divided in a 7:3 ratio into a training set (151 patients) and a validation set (65 patients). A nomogram model was constructed using univariate and multivariate logistic regression analyses. The predictive capability of the model was assessed using Receiver Operating Characteristic (ROC) curve analysis, comparing the predictive value based on the area under the ROC curve (AUC). RESULTS: In the training set, IMH post-PCI was observed in 78 AMI patients on CMR, while 73 did not show IMH. Variables with a significance level of P < 0.05 were screened using univariate logistic regression analysis. Twelve indicators were selected for multivariate logistic regression analysis: heart rate, diastolic blood pressure, ST segment elevation on electrocardiogram, culprit vessel, symptom onset to reperfusion time, C-reactive protein, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, creatine kinase-MB, high-sensitivity troponin T (HS-TnT), and SYNTAX Score. Based on multivariate logistic regression results, two independent predictive factors were identified: HS-TnT (Odds Ratio [OR] = 1.61, 95% Confidence Interval [CI]: 1.21-2.25, P = 0.003) and SS (OR = 2.54, 95% CI: 1.42-4.90, P = 0.003). Consequently, a nomogram model was constructed based on these findings. The AUC of the nomogram model in the training set was 0.893 (95% CI: 0.840-0.946), and in the validation set, it was 0.910 (95% CI: 0.823-0.970). Good consistency and accuracy of the model were demonstrated by calibration and decision curve analysis. CONCLUSION: The nomogram model, constructed utilizing HS-TnT and SS, demonstrates accurate predictive capability for the risk of IMH post-PCI in patients with AMI. This model offers significant guidance and theoretical support for the clinical diagnosis and treatment of these patients.

Exploring temperature-responsive drug delivery with biocompatible fatty acids as phase change materials in ethyl cellulose nanofibers.

This study introduces a novel temperature-responsive drug delivery system using ethyl cellulose (EC) nanofibers encapsulating a eutectic mixture of lauric acid/stearic acid (LA/SA) as phase change materials (PCMs) and Rhodamine B (RhB) as a model drug. Employing blend electrospinning, the nanofibers achieved controlled drug release responsive to temperature changes. The peak shift of the carbonyl group in FTIR analysis confirmed drug-polymer compatibility, while the absence of RhB peaks in the XRD and DSC assessments revealed RhB's amorphous distribution within the fibers. Our findings demonstrate that RhB release is dependent on its loading, with a slow initial release (<2 %) for 1 % and 5 % RhB loadings and a burst release (~12 %) for 10 % loading. Notably, the release rate was tunable at 37 °C by adjusting LA/SA concentration. The optimal LA/SA loading for temperature-responsive release is identified as 10 %. Over 240 h, there is a 32 % increase in RhB release at 37 °C, and an additional 8 % increase at 40 °C, compared to 25 °C. This research illustrates the potential of PCM-integrated nanofibers in smart drug delivery, particularly for chemotherapy, antibiotics, and anti-inflammatory drugs, showcasing an innovative approach to improving therapeutic efficiency while reducing side effects.

2.5D UNet with context-aware feature sequence fusion for accurate esophageal tumor semantic segmentation.

Segmenting esophageal tumor from computed tomography (CT) sequence images can assist doctors in diagnosing and treating patients with this malignancy. However, accurately extracting esophageal tumor features from CT images often present challenges due to their small area, variable position, and shape, as well as the low contrast with surrounding tissues. This results in not achieving the level of accuracy required for practical applications in current methods. To address this problem, we propose a 2.5D context-aware feature sequence fusion UNet (2.5D CFSF-UNet) model for esophageal tumor segmentation in CT sequence images. Specifically, we embed intra-slice multiscale attention feature fusion (Intra-slice MAFF) in each skip connection of UNet to improve feature learning capabilities, better expressing the differences between anatomical structures within CT sequence images. Additionally, the inter-slice context fusion block (Inter-slice CFB) is utilized in the center bridge of UNet to enhance the depiction of context features between CT slices, thereby preventing the loss of structural information between slices. Experiments are conducted on a dataset of 430 esophageal tumor patients. The results show an 87.13% dice similarity coefficient, a 79.71% intersection over union and a 2.4758 mm Hausdorff distance, which demonstrates that our approach can improve contouring consistency and can be applied to clinical applications.

Identification and biochemical characterization of a carboxylesterase gene associated with ß-cypermethrin resistance in Dermanyssus gallinae.

Dermanyssus gallinae is a major hematophagous ectoparasite in layer hens. Although the acaricide ß-cypermethrin has been used to control mites worldwide, D. gallinae has developed resistance to this compound. Carboxylesterases (CarEs) are important detoxification enzymes that confer resistance to ß-cypermethrin in arthropods. However, CarEs associated with ß-cypermethrin resistance in D. gallinae have not yet been functionally characterized. Here, we isolated a CarE gene (Deg-CarE) from D. gallinae and assayed its activity. The results revealed significantly higher expression of Deg-CarE in the ß-cypermethrin-resistant strain (RS) than in the susceptible strain (SS) toward α-naphthyl acetate (α-NA) and ß-naphthyl acetate (ß-NA). These findings suggest that enhanced esterase activities might have contributed to ß-cypermethrin resistance in D. gallinae. Quantitative real-time PCR analysis revealed that Deg-CarE expression levels were significantly higher in adults than in other life stages. Although Deg-CarE was upregulated in the RS, significant differences in gene copy numbers were not observed. Additionally, Deg-CarE expression was significantly induced by ß-cypermethrin in both the SS and RS. Moreover, silencing Deg-CarE via RNA interference decreased the enzyme activity and increased the susceptibility of the RS to ß-cypermethrin, confirming that Deg-CarE is crucial for ß-cypermethrin detoxification. Finally, recombinant Deg-CarE (rDeg-CarE) expressed in Escherichia coli displayed high enzymatic activity toward α/ß-NA. However, metabolic analysis indicated that rDeg-CarE did not directly metabolize ß-cypermethrin. The collective findings indicate that D. gallinae resistance to ß-cypermethrin is associated with elevated CarEs protein activity and increased Deg-CarE expression levels. These findings provide insights into the metabolic resistance of D. gallinae and offer scientific guidance for the management and control of D. gallinae.

Strong Linearly Polarized Light Emission by Coupling Out-of-Plane Exciton to Anisotropic Gap Plasmon Nanocavity.

With exceptional quantum confinement, 2D monolayer semiconductors support a strong excitonic effect, making them an ideal platform for exploring light-matter interactions and as building blocks for novel optoelectronic devices. Different from the well-known in-plane excitons in transition metal dichalcogenides (TMD), the out-of-plane excitons in indium selenide (InSe) usually show weak emission, which limits their applications as light sources. Here, by embedding InSe in an anisotropic gap plasmon nanocavity, we have realized plasmon-enhanced linearly polarized photoluminescence with an anisotropic ratio up to ∼140, corresponding to degree of polarization (DoP) of ∼98.6%. Such polarization selectivity, originating from the polarization-dependent plasmonic enhancement supported by the "nanowire-on-mirror" nanocavity, can be well tuned by the InSe thickness. Moreover, we have also realized an InSe-based light-emitting diode with polarized electroluminescence. Our research highlights the role of excitonic dipole orientation in designing nanophotonic devices and paves the way for developing InSe-based optoelectronic devices with polarization control.

Interactions between nitrogen and phosphorus modulate the food quality of the marine crop Pyropia haitanensis (T. J. Chang & B. F. Zheng) N. Kikuchi & M. Miyata (Porphyra haitanensis).

The quality of Pyropia haitanensis (T. J. Chang & B. F. Zheng) N. Kikuchi & M. Miyata (Porphyra haitanensis) is directly affected by nutrient availability. However, the molecular mechanism underlying the synergistic regulatory effects of nitrogen (N) and phosphorus (P) availability on P. haitanensis quality is unknown. Here, we performed physiological and multi-omics analyses to reveal the combined effects of N and P on P. haitanensis quality. The pigments accumulated under high N because of increases in N metabolism and porphyrin metabolism, ultimately resulting in intensely colored thalli. High N also promoted amino acid metabolism and inosine 5'-mononucleotide (IMP) synthesis, but inhibited carbohydrates accumulation. This resulted in increased amino acid, IMP and decreased agaro-carrageenan and cellulose contents, thereby improving the nutritional value and taste. Furthermore, high P promoted carbon metabolism and amino acid metabolism.This study provided the basis for elucidating the mechanism behind N and P regulating the seaweed quality.

Intraoperative mechanical ventilation and incidence of pneumothorax in lymphangioleiomyomatosis.

Patients with lymphangioleiomyomatosis (LAM) are considered high risk for most surgeries and require specific anesthetic considerations mainly because of the common spontaneous pneumothorax (PTX). To explore whether intraoperative mechanical ventilation could increase the risk of PTX in those patients, we included 12 surgical patients with LAM in this study, of whom four (33.3%) experienced postoperative PTX. According to our results, patients with higher CT grade, poorer pulmonary function, and a history of preoperative PTX might be more likely to develop postoperative PTX. However, intraoperative mechanical ventilation did not show obvious influence, which might help clinicians reconsider the perioperative management of LAM patients.