Neurotoxicity from long-term exposure to 6-PPDQ: Recent advances.

The recent acceleration of industrialization and urbanization has brought significant attention to N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6-PPDQ), an emerging environmental pollutant from tire wear, due to its long-term effects on the environment and organisms. Recent studies suggest that 6-PPDQ can disrupt neurotransmitter synthesis and release, impact receptor function, and alter signaling pathways, potentially causing oxidative stress, inflammation, and apoptosis. This review investigates the potential neurotoxic effects of prolonged 6-PPDQ exposure, the mechanisms underlying its cytotoxicity, and the associated health risks. We emphasize the need for future research, including precise exposure assessments, identification of individual differences, and development of risk assessments and intervention strategies. This article provides a comprehensive overview of 6-PPDQ's behavior, impact, and neurotoxicity in the environment, highlighting key areas and challenges for future research.

Nonlinear compliance of NompC gating spring and its implication in mechanotransduction.

Cytoskeleton-tethered mechanosensitive channels (MSCs) utilize compliant proteins or protein domains called gating springs to convert mechanical stimuli into electric signals, enabling sound and touch sensation and proprioception. The mechanical properties of these gating springs, however, remain elusive. Here, we explored the mechanical properties of the homotetrameric NompC complex containing long ankyrin-repeat domains (ARDs). We developed a toehold-mediated strand displacement approach to tether single membrane proteins, allowing us to exert force on them and precisely measure their absolute extension using optical tweezers. Our findings revealed that each ARD has a low stiffness of ~0.7 pN/nm and begins to unfold stepwise at ~7 pN, leading to nonlinear compliance. Our calculations indicate that this nonlinear compliance may help regulate NompC's sensitivity, dynamic range, and kinetics to detect mechanical stimuli. Overall, our research highlights the importance of a compliant and unfolding-refolding gating spring in facilitating a graded response of MSC ion transduction across a wide spectrum of mechanical stimuli.

Habitat radiomics and deep learning fusion nomogram to predict EGFR mutation status in stage I non-small cell lung cancer: a multicenter study.

Develop a radiomics nomogram that integrates deep learning, radiomics, and clinical variables to predict epidermal growth factor receptor (EGFR) mutation status in patients with stage I non-small cell lung cancer (NSCLC). We retrospectively included 438 patients who underwent curative surgery and completed driver-gene mutation tests for stage I NSCLC from four academic medical centers. Predictive models were established by extracting and analyzing radiomic features in intratumoral, peritumoral, and habitat regions of CT images to identify EGFR mutation status in stage I NSCLC. Additionally, three deep learning models based on the intratumoral region were constructed. A nomogram was developed by integrating representative radiomic signatures, deep learning, and clinical features. Model performance was assessed by calculating the area under the receiver operating characteristic (ROC) curve. The established habitat radiomics features demonstrated encouraging performance in discriminating between EGFR mutant and wild-type, with predictive ability superior to other single models (AUC 0.886, 0.812, and 0.790 for the training, validation, and external test sets, respectively). The radiomics-based nomogram exhibited excellent performance, achieving the highest AUC values of 0.917, 0.837, and 0.809 in the training, validation, and external test sets, respectively. Decision curve analysis (DCA) indicated that the nomogram provided a higher net benefit than other radiomics models, offering valuable information for treatment.

Decoding the role of DNA methylation in allergic diseases: from pathogenesis to therapy.

Allergic diseases, characterized by a broad spectrum of clinical manifestations and symptoms, encompass a significant category of IgE-mediated atopic disorders, including asthma, allergic rhinitis, atopic dermatitis, and food allergies. These complex conditions arise from the intricate interplay between genetic and environmental factors and are known to contribute to socioeconomic burdens globally. Recent advancements in the study of allergic diseases have illuminated the crucial role of DNA methylation (DNAm) in their pathogenesis. This review explores the factors influencing DNAm in allergic diseases and delves into their mechanisms, offering valuable perspectives for clinicians. Understanding these epigenetic modifications aims to lay the groundwork for improved early prevention strategies. Moreover, our analysis of DNAm mechanisms in these conditions seeks to enhance diagnostic and therapeutic approaches, paving the way for more effective management of allergic diseases in the future.

NAD metabolism-related genes provide prognostic value and potential therapeutic insights for acute myeloid leukemia.

Introduction: Acute myeloid leukemia (AML) is an aggressive blood cancer with high heterogeneity and poor prognosis. Although the metabolic reprogramming of nicotinamide adenine dinucleotide (NAD) has been reported to play a pivotal role in the pathogenesis of acute myeloid leukemia (AML), the prognostic value of NAD metabolism and its correlation with the immune microenvironment in AML remains unclear. Methods: We utilized our large-scale RNA-seq data on 655 patients with AML and the NAD metabolism-related genes to establish a prognostic NAD metabolism score based on the sparse regression analysis. The signature was validated across three independent datasets including a total of 1,215 AML patients. ssGSEA and ESTIMATE algorithms were employed to dissect the tumor immune microenvironment. Ex vivo drug screening and in vitro experimental validation were performed to identify potential therapeutic approaches for the high-risk patients. In vitro knockdown and functional experiments were employed to investigate the role of SLC25A51, a mitochondrial NAD+ transporter gene implicated in the signature. Results: An 8-gene NAD metabolism signature (NADM8) was generated and demonstrated a robust prognostic value in more than 1,800 patients with AML. High NADM8 score could efficiently discriminate AML patients with adverse clinical characteristics and genetic lesions and serve as an independent factor predicting a poor prognosis. Immune microenvironment analysis revealed significant enrichment of distinct tumor-infiltrating immune cells and activation of immune checkpoints in patients with high NADM8 scores, acting as a potential biomarker for immune response evaluation in AML. Furthermore, ex vivo drug screening and in vitro experimental validation in a panel of 9 AML cell lines demonstrated that the patients with high NADM8 scores were more sensitive to the PI3K inhibitor, GDC-0914. Finally, functional experiments also substantiated the critical pathogenic role of the SLC25A51 in AML, which could be a promising therapeutic target. Conclusion: Our study demonstrated that NAD metabolism-related signature can facilitate risk stratification and prognosis prediction in AML and guide therapeutic decisions including both immunotherapy and targeted therapies.

γ-aminobutyric acid treatment inhibits browning and promotes storage quality by regulating reactive oxygen species and membrane lipid metabolism in fresh-cut stem lettuce.

The effects of γ-aminobutyric (GABA) on enzymatic browning, storage quality, membrane and reactive oxygen species (ROS) metabolism in fresh-cut stem lettuce were investigated. The results illustrated that GABA treatment delayed browning degree, polyphenol oxidase (PPO) activity and the expression of LsPPO. Meanwhile, higher chlorophyll and ascorbic acid contents were exhibited in GABA-treated stem lettuce, as well as the slower microbial propagation. Further investigation revealed that exogenous GABA application declined malondialdehyde content, electrolyte leakage and the enzyme activities of membrane metabolism, and the expression levels of related genes were also downregulated. In addition, GABA treatment scavenged ROS and strengthened the enzyme activities of ROS metabolism, as well as the expression levels of corresponding genes. Taken together, these findings implied that the repressed enzymatic browning and microbial propagation in GABA-treated stem lettuce were due to the inhibition of ROS accumulation, enhancement of membrane stability and increased resistance to oxidation.

"Top-down" overexpression optimization of Butelase 1 in Escherichia coli and its application in anti-tumor peptides.

Butelase 1, the fastest known Asn/Asp-specific peptide ligase capable of catalyzing peptide ligation and cyclization, holds promising application prospects in the fields of food and biology. However, limited research exists on its recombinant expression and potential applications in peptide drugs. In this study, the activity of recombinantly-produced butelase 1 was enhanced by co-expressing it with a molecular chaperone in the SHuffle T7 strain. By introducing single or multiple synonymous rare codons at the beginning of the coding regions of beta-strand or alpha-helix, in combination with ribosomal binding site engineering, the activity of butelase 1 could be further improved. Consequently, the butelase 1 with a specific activity of 386.93 U/mg and a catalytic efficiency of 11,048 M-1 s-1 was successfully prepared in E. coli, resulting in a total activity of 8183.54 U/L and a yield of about 100 mg/L. This optimized butelase 1 was then used to efficiently cyclize the redesigned anti-cancer peptide lunasin, leading to enhanced bioavailability and anti-cancer effects. Overall, this study not only provided valuable biotechnology strategies for improving the recombinant expression of butelase 1 but also demonstrated a successful application for enhancing the biological efficacy of anti-cancer peptides.

A syrup containing L-arabinose and D-xylose appears superior to PEG-4000 as a bowel cleansing agent.

Adequate bowel cleansing is crucial for endoscopic diagnosis and treatment, and the recovery of gut microbiota after intestinal cleansing is also important. A hypertonic syrup predominantly comprising L-arabinose and D-xylose (20% xylo-oligosaccharides) can be extracted from the hemicellulose of corn husks and cobs. L-Arabinose and xylo-oligosaccharides have been reported to relieve constipation and improve the gut microbial environment. This study evaluated the bowel cleansing effect of the aforementioned syrup and its influence on the organism and intestinal microbiota after cleansing in comparison with polyethylene glycol-4000 (PEG-4000) in mice. Bowel cleansing was performed using syrup or PEG-4000 in C57BL/6J mice, and the effect of intestinal preparation and its influence on serum electrolytes and gut microbiota after bowel cleansing were evaluated. The volume of intestinal residual feces in the syrup group was significantly lower than that in the PEG-4000 group. Additionally, syrup disturbed serum electrolytes more mildly than PEG-4000. Alpha diversity in the gut microbiota was significantly higher in the syrup group than in the PEG-4000 group on the first day after bowel cleansing. However, no difference in beta diversity was observed between the two groups. Syrup increased the abundance of Bifidobacteria and Christensenella and decreased the abundance of Akkermansia in comparison with PEG-4000 on the first day after bowel cleansing. Thus, this syrup has potential clinical use as a bowel cleansing agent given the above effects, its benefits and safety, and better taste and acceptability.

The adaptive mechanisms of the marine diatom Thalassiosira weissflogii to long-term high CO2 and warming.

While it is known that increased dissolved CO2 concentrations and rising sea surface temperature (ocean warming) can act interactively on marine phytoplankton, the ultimate molecular mechanisms underlying this interaction on a long-term evolutionary scale are relatively unexplored. Here, we performed transcriptomics and quantitative metabolomics analyses, along with a physiological trait analysis, on the marine diatom Thalassiosira weissflogii adapted for approximately 3.5 years to warming and/or high CO2 conditions. We show that long-term warming has more pronounced impacts than elevated CO2 on gene expression, resulting in a greater number of differentially expressed genes (DEGs). The largest number of DEGs was observed in populations adapted to warming + high CO2, indicating a potential synergistic interaction between these factors. We further identified the metabolic pathways in which the DEGs function and the metabolites with significantly changed abundances. We found that ribosome biosynthesis-related pathways were upregulated to meet the increased material and energy demands after warming or warming in combination with high CO2. This resulted in the upregulation of energy metabolism pathways such as glycolysis, photorespiration, the tricarboxylic acid cycle, and the oxidative pentose phosphate pathway, as well as the associated metabolites. These metabolic changes help compensate for reduced photochemical efficiency and photosynthesis. Our study emphasizes that the upregulation of ribosome biosynthesis plays an essential role in facilitating the adaptation of phytoplankton to global ocean changes and elucidates the interactive effects of warming and high CO2 on the adaptation of marine phytoplankton in the context of global change.

Establishment of a Mouse Model of Mycoplasma pneumoniae-Induced Plastic Bronchitis.

Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed to Mycoplasma pneumoniae (MP) infection. The pathogenic mechanisms involved remain largely unexplored, leading to the absence of reliable approaches for early diagnosis and clear treatment. Thus, the present investigation aimed to develop an MP-induced mouse model of PB, thereby enhancing our understanding of this complex condition. In the first stage, healthy BALB/c mice were utilized to investigate the optimal methods for establishing PB. This involved the application of nebulization (15-20 min) and intratracheal administration (6-50 µL) with 2-chloroethyl ethyl sulfide (CEES) concentrations ranging from 4.5% to 7.5%. Subsequently, the MP model was induced by administering an MP solution (2 mL/kg/day, 108 CFU/50 µL) via the intranasal route for a duration of five consecutive days. Ultimately, suitable techniques were employed to induce plastic bronchitis in the MP model. Pathological changes in lung tissue were analyzed, and immunohistochemistry was employed to ascertain the expression levels of vascular endothelial growth factor receptor 3 (VEGFR-3) and the PI3K/AKT/mTOR signaling pathway. The administration of 4.5% CEES via a 6 µL trachea was the optimal approach to establishing a PB model. This method primarily induced neutrophilic inflammation and fibrinous exudate. The MP-infected group manifested symptoms indicative of respiratory infection, including erect hair, oral and nasal secretions, and a decrease in body weight. Furthermore, the pathological score of the MP+CEES group surpassed that of the groups treated with MP or CEES independently. Notably, the MP+CEES group demonstrated significant activation of the VEGFR-3 and PI3K/AKT/mTOR signaling pathways, implying a substantial involvement of lymphatic vessel impairment in this pathology. This study successfully established a mouse model of PB induced by MP using a two-step method. Lymphatic vessel impairment is a pivotal element in the pathogenetic mechanisms underlying this disease entity. This accomplishment will aid in further research into treatment methods for patients with PB caused by MP.

Standard-definition White-light, High-definition White-light versus Narrow-band Imaging Endoscopy for Detecting Colorectal Adenomas: A Multicenter Randomized Controlled Trial.

OBJECTIVE: This study aimed to compare the performance of standard-definition white-light endoscopy (SD-WL), high-definition white-light endoscopy (HD-WL), and high-definition narrow-band imaging (HD-NBI) in detecting colorectal lesions in the Chinese population. METHODS: This was a multicenter, single-blind, randomized, controlled trial with a non-inferiority design. Patients undergoing endoscopy for physical examination, screening, and surveillance were enrolled from July 2017 to December 2020. The primary outcome measure was the adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma detected. The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression. RESULTS: Out of 653 eligible patients enrolled, data from 596 patients were analyzed. The ADRs were 34.5% in the SD-WL group, 33.5% in the HD-WL group, and 37.5% in the HD-NBI group (P=0.72). The advanced neoplasm detection rates (ANDRs) in the three arms were 17.1%, 15.5%, and 10.4% (P=0.17). No significant differences were found between the SD group and HD group regarding ADR or ANDR (ADR: 34.5% vs. 35.6%, P=0.79; ANDR: 17.1% vs. 13.0%, P=0.16, respectively). Similar results were observed between the HD-WL group and HD-NBI group (ADR: 33.5% vs. 37.7%, P=0.45; ANDR: 15.5% vs. 10.4%, P=0.18, respectively). In the univariate and multivariate logistic regression analyses, neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL (HD-WL: OR 0.91, P=0.69; HD-NBI: OR 1.15, P=0.80). CONCLUSION: HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients. It can be concluded that HD-NBI or HD-WL is not superior to SD-WL, but more effective instruction may be needed to guide the selection of different endoscopic methods in the future. Our study's conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources, especially advanced imaging technologies.

The sphingosine-1-phosphate receptor 1 mediates the atheroprotective effect of eicosapentaenoic acid.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been associated with potential cardiovascular benefits, partly attributed to their bioactive metabolites. However, the underlying mechanisms responsible for these advantages are not fully understood. We previously reported that metabolites of the cytochrome P450 pathway derived from eicosapentaenoic acid (EPA) mediated the atheroprotective effect of ω-3 PUFAs. Here, we show that 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and its receptor, sphingosine-1-phosphate receptor 1 (S1PR1), in endothelial cells (ECs) can inhibit oscillatory shear stress- or tumor necrosis factor-α-induced endothelial activation in cultured human ECs. Notably, the atheroprotective effect of 17,18-EEQ and purified EPA is circumvented in male mice with endothelial S1PR1 deficiency. Mechanistically, the anti-inflammatory effect of 17,18-EEQ relies on calcium release-mediated endothelial nitric oxide synthase (eNOS) activation, which is abolished upon inhibition of S1PR1 or Gq signaling. Furthermore, 17,18-EEQ allosterically regulates the conformation of S1PR1 through a polar interaction with Lys34Nter. Finally, we show that Vascepa, a prescription drug containing highly purified and stable EPA ethyl ester, exerts its cardiovascular protective effect through the 17,18-EEQ-S1PR1 pathway in male and female mice. Collectively, our findings indicate that the anti-inflammatory effect of 17,18-EEQ involves the activation of the S1PR1-Gq-Ca2+-eNOS axis in ECs, offering a potential therapeutic target against atherosclerosis.

Oncogenic and immunological role of EDIL3 in human tumours: From pan-cancer analysis to validation in gastric cancer.

Background: Epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) is a secreted extracellular matrix protein implicated in diverse physiological and pathological processes including embryonic development, angiogenesis, and anti-inflammatory responses. Recent reports have indicated that EDIL3 play critical roles in carcinogenesis and progression of many cancers. Herein, we performed a pan-cancer investigation to study the potential functions of EDIL3 in various cancers and experimentally validate its function in gastric cancer (GC). Methods: We analysed EDIL3 expression profiles in different tumours using The Cancer Genome Atlas database. The Kaplan-Meier Plotter was used to investigate the prognostic value of EDIL3, while receiver operating characteristic curve was performed to analyze its diagnostic efficacy. Several bioinformatics tools were used to study the association between EDIL3 and promoter methylation, gene enrichment analysis, immune infiltration, immune-related genes, and drug sensitivity. Molecular biology experiments were conducted to validate the tumorigenic effects of EDIL3. Results: EDIL3 is variably expressed in different cancers and is closely associated with clinical outcomes. An inverse correlation between EDIL3 and DNA methylation has been observed in 13 cancers. Enrichment analysis indicated that EDIL3 is correlated with many cellular pathways such as extracellular matrix receptor interactions and focal adhesion. EDIL3 was tightly associated with immune infiltration and immune checkpoints. EDIL3 knockdown can promote GC calls apoptosis while preventing proliferation, migration, and invasion in vitro. Conclusion: EDIL3 is a promising prognostic, diagnostic, and immunological biomarker in various cancers, which could be applied as a new target for cancer therapy.

Mycoplasma pneumoniae pneumonia-associated thromboembolism with plastic bronchitis: a series of five case reports and literature review.

BACKGROUND: Mycoplasma pneumoniae pneumonia is a common respiratory infection among children. However, the occurrence of thromboembolism with plastic bronchitis in association with Mycoplasma pneumoniae pneumonia is extremely rare. This case series presents five cases of children with Mycoplasma pneumoniae pneumonia who developed thromboembolism and plastic bronchitis. The clinical presentation, diagnostic approach, and management strategies are discussed. METHODS: A retrospective analysis was conducted on medical records from a pediatric hospital. Patient demographics, clinical features, laboratory findings, imaging results, treatment modalities, and outcomes were collected. RESULTS: The patients in our case series presented with varying degrees of respiratory distress, cough, and fever. Imaging studies revealed evidence of thromboembolism based on pulmonary artery occlusion. Bronchial casts were observed by bronchoscopy. Laboratory tests demonstrated elevated D-dimer levels and fibrinogen degradation products. All patients received a combination of low molecular weight heparin anticoagulation and supportive care. CONCLUSION: Thromboembolism with plastic bronchitis associated with Mycoplasma pneumoniae pneumonia is a rare but potentially serious complication in children. Prompt recognition and management are crucial for improving patient outcomes. This case series highlights the diverse clinical presentations, diagnostic challenges, and treatment strategies for this unique clinical entity. Further research is needed to better understand the pathogenesis and optimal management of this condition.

Experimental and Numerical Investigation Integrated with Machine Learning (ML) for the Prediction Strategy of DP590/CFRP Composite Laminates.

This study unveils a machine learning (ML)-assisted framework designed to optimize the stacking sequence and orientation of carbon fiber-reinforced polymer (CFRP)/metal composite laminates, aiming to enhance their mechanical properties under quasi-static loading conditions. This work pioneers the expansion of initial datasets for ML analysis in the field by uniquely integrating the experimental results with finite element simulations. Nine ML models, including XGBoost and gradient boosting, were assessed for their precision in predicting tensile and bending strengths. The findings reveal that the XGBoost and gradient boosting models excel in tensile strength prediction due to their low error rates and high interpretability. In contrast, the decision trees, K-nearest neighbors (KNN), and random forest models show the highest accuracy in bending strength predictions. Tree-based models demonstrated exceptional performance across various metrics, notably for CFRP/DP590 laminates. Additionally, this study investigates the impact of layup sequences on mechanical properties, employing an innovative combination of ML, numerical, and experimental approaches. The novelty of this study lies in the first-time application of these ML models to the performance optimization of CFRP/metal composites and in providing a novel perspective through the comprehensive integration of experimental, numerical, and ML methods for composite material design and performance prediction.

An AS-OCT image dataset for deep learning-enabled segmentation and 3D reconstruction for keratitis.

Infectious keratitis is among the major causes of global blindness. Anterior segment optical coherence tomography (AS-OCT) images allow the characterizing of cross-sectional structures in the cornea with keratitis thus revealing the severity of inflammation, and can also provide 360-degree information on anterior chambers. The development of image analysis methods for such cases, particularly deep learning methods, requires a large number of annotated images, but to date, there is no such open-access AS-OCT image repository. For this reason, this work provides a dataset containing a total of 1168 AS-OCT images of patients with keratitis, including 768 full-frame images (6 patients). Each image has associated segmentation labels for lesions and cornea, and also labels of iris for full-frame images. This study provides a great opportunity to advance the field of image analysis on AS-OCT images in both two-dimensional (2D) and three-dimensional (3D) and would aid in the development of artificial intelligence-based keratitis management.

General In Situ Engineering of Carbon-Based Materials on Carbon Fiber for In Vivo Neurochemical Sensing.

Developing real-time, dynamic, and in situ analytical methods with high spatial and temporal resolutions is crucial for exploring biochemical processes in the brain. Although in vivo electrochemical methods based on carbon fiber (CF) microelectrodes are effective in monitoring neurochemical dynamics during physiological and pathological processes, complex post modification hinders large-scale productions and widespread neuroscience applications. Herein, we develop a general strategy for the in situ engineering of carbon-based materials to mass-produce functional CFs by introducing polydopamine to anchor zeolitic imidazolate frameworks as precursors, followed by one-step pyrolysis. This strategy demonstrates exceptional universality and design flexibility, overcoming complex post-modification procedures and avoiding the delamination of the modification layer. This simplifies the fabrication and integration of functional CF-based microelectrodes. Moreover, we design highly stable and selective H+, O2, and ascorbate microsensors and monitor the influence of CO2 exposure on the O2 content of the cerebral tissue during physiological and ischemia-reperfusion pathological processes.

Vaccarin alleviates septic cardiomyopathy by potentiating NLRP3 palmitoylation and inactivation.

BACKGROUND: Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1ß and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction. PURPOSE: The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms. STUDY DESIGN: The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice. METHODS/RESULTS: Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC. CONCLUSION: Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM.

Clinical Efficacy of Percutaneous Osteoplasty Under Fluoroscopy and Cone-Beam CT Guidance for Painful Sternal Metastases: A Case Series.

Background: Although percutaneous osteoplasty (POP) has been widely accepted and is now being performed for the treatment of painful bone metastases outside the spine. It is emerging as one of the most promising procedures for patients with painful bone metastasis who are unsuitable for surgery or who show resistance to radiotherapy and/or analgesic therapies. However, there are only scarce reports regarding osteoplasty in painful sternal metastases. Subjects and Method: We report four patients with sternal metastases suffered with severe pain of anterior chest wall. The original tumors included lung cancer and thyroid cancer. For the initially pain medication failing, all the four patients received POP procedure under fluoroscopic and cone-beam CT (CBCT) guidance, and obtained satisfying resolution of painful symptoms at 6-month postop follow-up. Conclusion: POP is a safe and effective treatment for pain caused by metastatic bone tumors in the sternum. In practice, however, percutaneous puncture of pathologic sternal fractures can be a challenge because of the long flat contour and the defacement by lytic tumor of bony landmarks. We find that the use of fluoroscopic and CBCT can facilitate POP for flat bone fractures with displacing the trajectory planning, needle advancement, and cement delivery in time.

Potential Gradient-Driven Dual-Functional Electrochromic and Electrochemical Device Based on a Shared Electrode Design.

The integration of electrochromic devices and energy storage systems in wearable electronics is highly desirable yet challenging, because self-powered electrochromic devices often require an open system design for continuous replenishment of the strong oxidants to enable the coloring/bleaching processes. A self-powered electrochromic device has been developed with a close configuration by integrating a Zn/MnO2 ionic battery into the Prussian blue (PB)-based electrochromic system. Zn and MnO2 electrodes, as dual shared electrodes, the former one can reduce the PB electrode to the Prussian white (PW) electrode and serves as the anode in the battery; the latter electrode can oxidize the PW electrode to its initial state and acts as the cathode in the battery. The bleaching/coloring processes are driven by the gradient potential between Zn/PB and PW/MnO2 electrodes. The as-prepared Zn||PB||MnO2 system demonstrates superior electrochromic performance, including excellent optical contrast (80.6%), fast self-bleaching/coloring speed (2.0/3.2 s for bleaching/coloring), and long-term self-powered electrochromic cycles. An air-working Zn||PB||MnO2 device is also developed with a 70.3% optical contrast, fast switching speed (2.2/4.8 s for bleaching/coloring), and over 80 self-bleaching/coloring cycles. Furthermore, the closed nature enables the fabrication of various flexible electrochromic devices, exhibiting great potentials for the next-generation wearable electrochromic devices.