DDX5 inhibits inflammation by modulating m6A levels of TLR2/4 transcripts during bacterial infection.

DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.

KDM6A-SND1 interaction maintains genomic stability by protecting the nascent DNA and contributes to cancer chemoresistance.

Genomic instability is one of the hallmarks of cancer. While loss of histone demethylase KDM6A increases the risk of tumorigenesis, its specific role in maintaining genomic stability remains poorly understood. Here, we propose a mechanism in which KDM6A maintains genomic stability independently on its demethylase activity. This occurs through its interaction with SND1, resulting in the establishment of a protective chromatin state that prevents replication fork collapse by recruiting of RPA and Ku70 to nascent DNA strand. Notably, KDM6A-SND1 interaction is up-regulated by KDM6A SUMOylation, while KDM6AK90A mutation almost abolish the interaction. Loss of KDM6A or SND1 leads to increased enrichment of H3K9ac and H4K8ac but attenuates the enrichment of Ku70 and H3K4me3 at nascent DNA strand. This subsequently results in enhanced cellular sensitivity to genotoxins and genomic instability. Consistent with these findings, knockdown of KDM6A and SND1 in esophageal squamous cell carcinoma (ESCC) cells increases genotoxin sensitivity. Intriguingly, KDM6A H101D & P110S, N1156T and D1216N mutations identified in ESCC patients promote genotoxin resistance via increased SND1 association. Our finding provides novel insights into the pivotal role of KDM6A-SND1 in genomic stability and chemoresistance, implying that targeting KDM6A and/or its interaction with SND1 may be a promising strategy to overcome the chemoresistance.

Design and Fabrication of Biomass Derived Black Carbon Modified g-C3N4/FeIn2S4 Heterojunction as Highly Efficient Photocatalyst for Wastewater Treatment.

The environmental deterioration caused by dye wastewater discharge has received considerable attention in recent decades. One of the most promising approaches to addressing the aforementioned environmental issue is the development of photocatalysts with high solar energy consumption efficiency for the treatment of dye-contaminated water. In this study, a novel low-cost π-π biomass-derived black carbon modified g-C3N4 coupled FeIn2S4 composite (i.e., FeInS/BC-CN) photocatalyst is successfully designed and fabricated that reveals significantly improved photocatalytic performance for the degradation of Eosin Yellow (EY) dye in aqueous solution. Under dark and subsequent visible light irradiation, the amount optimized composite reveals 99% removal performance for EY dye, almost three-fold compared to that of the pristine FeInS and BC-CN counterparts. Further, it is confirmed by means of the electron spin resonance spectrometry, quenching experiments, and density functional theory (DFT) calculations, that the hydroxyl radicals (•OH) and superoxide radicals (•O2 -) are the dominant oxidation species involved in the degradation process of EY dye. In addition, a systematic photocatalytic degradation route is proposed based on the resultant degradation intermediates detectedduring liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. This work provides an innovative idea for the development of advanced photocatalysts to mitigate water pollution.

The therapeutic effect of a novel GAPDH inhibitor in mouse model of breast cancer and efficacy monitoring by molecular imaging.

BACKGROUND: Breast cancer is a serious threat to women's health with high morbidity and mortality. The development of more effective therapies for the treatment of breast cancer is strongly warranted. Growing evidence suggests that targeting glucose metabolism may be a promising cancer treatment strategy. We previously identified a new glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor, DC-5163, which shows great potential in inhibiting tumor growth. Here, we evaluated the anticancer potential of DC-5163 in breast cancer cells. METHODS: The effects of DC-5163 on breast cancer cells were investigated in vitro and in vivo. Seahorse, glucose uptake, lactate production, and cellular ATP content assays were performed to examine the impact of DC-5163 on cellular glycolysis. Cell viability, colony-forming ability, cell cycle, and apoptosis were assessed by CCK8 assay, colony formation assay, flow cytometry, and immunoblotting respectively. The anticancer activity of DC-5163 in vivo was evaluated in a mouse breast cancer xenograft model. RESULTS: DC-5163 suppressed aerobic glycolysis and reduced energy supply of breast cancer cells, thereby inhibiting breast cancer cell growth, inducing cell cycle arrest in the G0/G1 phase, and increasing apoptosis. The therapeutic efficacy was assessed using a breast cancer xenograft mouse model. DC-5163 treatment markedly suppressed tumor growth in vivo without inducing evident systemic toxicity. Micro-PET/CT scans revealed a notable reduction in tumor 18F-FDG and 18F-FLT uptake in the DC-5163 treatment group compared to the DMSO control group. CONCLUSIONS: Our results suggest that DC-5163 is a promising GAPDH inhibitor for suppressing breast cancer growth without obvious side effects. 18F-FDG and 18F-FLT PET/CT can noninvasively assess the levels of glycolysis and proliferation in tumors following treatment with DC-5163.

GOLPH3 knockdown alleviates the inflammation and apoptosis in lipopolysaccharide-induced acute lung injury by inhibiting Golgi stress mediated autophagy.

Pneumonia, an acute inflammatory lesion of the lung, is the leading cause of death in children aged < 5 years. We aimed to study the function and mechanism of Golgi phosphoprotein 3 (GOLPH3) in infantile pneumonia. Lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and injury of MLE-12 cells were used as the pneumonia model in vitro. After GOLPH3 was knocked down, the histopathological changes of lung tissues were assessed by hematoxylin-eosin (H&E) staining. The Wet/Dry ratio of lung tissues was calculated. The enzyme-linked immunosorbent assay (ELISA) method was used to detecte the contents of inflammatory factors in bronchoalveolar lavage fluid (BALF). The damaged DNA in apoptotic cells in lung tissues was tested by Terminal deoxynucleotidyl transferase-mediated dUTP Nick end labeling (TUNEL) staining. Immunofluorescence staining analyzed LC3II and Golgi matrix protein 130 (GM130) expression in lung tissues and MLE-12 cells. The apoptosis of MLE-12 cells was measured by flow cytometry analysis. Additionally, the expression of proteins related to apoptosis, autophagy and Golgi stress was examined with immunoblotting. Results indicated that GOLPH3 knockdown alleviated lung tissue pathological changes in LPS-triggered ALI mice. LPS-induced inflammation and apoptosis in lung tissues and MLE-12 cells were remarkably alleviated by GOLPH3 deficiency. Besides, GOLPH3 depletion suppressed autophagy and Golgi stress in lung tissues and MLE-12 cells challenged with LPS. Moreover, Rapamycin (Rap), an autophagy inhibitor, counteracted inflammation and apoptosis inhibited by GOLPH3 silencing in LPS-induced MLE-12 cells. Furthermore, brefeldin A (BFA) pretreatment apparently abrogated the inhibitory effect of GOLPH3 knockdown on autophagy in MLE-12 cells exposed to LPS. To be concluded, GOLPH3 knockdown exerted lung protective effect against LPS-triggered inflammation and apoptosis by inhibiting Golgi stress mediated autophagy.

Ti4+ Ions-Doped Metal-Organic Framework (MOF-74) for Photoreduction of Carbon Dioxide.

The development of efficient and sustainable methods for reducing carbon dioxide (CO2) and converting it into valuable hydrocarbons has gained significant attention. In this study, researchers focused on Ti4+-doped metal-organic framework (MOF-74) photocatalysts. The incorporation of Ti4+ ions into the MOF-74 structure was achieved through a one-pot hydrothermal method. By replacing Zn2+ ions with Ti4+ ions in a substitutional manner, researchers have aimed to enhance the photocatalytic activity of the CO2 reduction. The obtained Ti4+-doped MOF-74 photocatalysts exhibited a significantly improved performance in the reduction of CO2 into carbon monoxide (CO). The doping of Ti4+ ions induced energy bands below the conduction band minimum (CBM) of MOF-74, extending the visible response range and enabling the photocatalysts to utilize a broader spectrum of light for catalytic reactions. This extension of the visible response range enables photocatalysts to utilize a broader spectrum of light for catalytic reactions. The incorporation of Ti4+ ions not only extends the visible response range but also suppresses charge carrier recombination. This work provides valuable insights into the design principles of MOF-based photocatalysts and paves the way for their practical implementation in addressing the energy crisis and reducing greenhouse gas emissions.

Tissue-Specific Accumulation of Orally Administered Short- and Medium-Chain Chlorinated Paraffins in Honeybees (Apis mellifera L.).

The prevalence and distribution of chlorinated paraffins (CPs) have been extensively studied in various matrices and organisms; however, there is a lack of information about insects, particularly in honeybees. To address this gap, we studied young honeybee workers exposed to short- and medium-chain CPs (SCCPs and MCCPs) at an environmentally relevant concentration of 10 mg/L for 7 days, followed by a 7-day elimination period. Results indicated that CPs could transfer into the head after oral consumption and SCCPs and MCCPs exhibited clear bioaccumulation trends: midgut > hindgut > head. An evaluation of congener group distribution patterns demonstrated that the dominant congener groups in all target tissues were C11-13Cl7-8 and C14Cl7-8 for SCCPs and MCCPs, respectively, consistent with the treated CP standards. In honeybees, a significant negative relationship was observed for the log concentration of MCCP congener groups and their log KOW, but not with their log KOA. Conversely, no such correlation was found for SCCPs. These findings suggest that honeybees have a high potential to bioaccumulate MCCPs, particularly those with a low log KOW, and exhibit weak selectivity for SCCPs.

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.

Chlorinated paraffins in takeout food and its packaging in Beijing, China and dietary exposure risk.

Chlorinated paraffins (CPs) are hazardous to humans, and dietary intake acts as the primary pathway for human exposure to CPs. Takeout food is popular worldwide, but the presence of CPs in takeout food and its packaging is unclear. In this study, the concentrations and distributions of short- and median-chain CPs (SCCPs and MCCPs, respectively) were measured in 97 samples of four categories of takeout food and 33 samples of three types of takeout packaging. The SCCP and MCCP median concentrations for the takeout food samples were 248 and 339, 77.2 and 98.2, 118 and 258, 42.9 and 64.4 ng/g wet weight in meat, starch, half meat/half starch, and vegetables, respectively. Takeout food contained higher concentrations of SCCPs than MCCPs. The dominant SCCP and MCCP congener groups in takeout food were C10Cl6-7 and C14Cl7-8, respectively. The CP concentrations in takeout food were lower than those in packaging. The SCCP and MCCP median concentrations, respectively, in packaging were 9750 and 245 ng/g in polypropylene, 2830 and 135 ng/g in paper, and 2060 and 119 ng/g in aluminum foil. The concentrations of SCCPs and MCCPs were comparable in aluminum foil, whereas the concentrations of SCCPs were higher than those of MCCPs in polypropylene and paper. Correlations between CP concentrations in the takeout food and packaging indicated that CPs in packaging were potentially an important source of CPs in the takeout food. A dietary exposure risk assessment showed the takeout food posed a low risk for human exposure to CPs; however, high-frequency consumption may pose a health risk. This study clarified the current contamination situation in takeout food in Beijing, China. The resulting data could be used to prevent human exposure to CPs through dietary intake and to facilitate the market's control over the quality of takeout food.

A preliminary study on short- and medium-chain chlorinated paraffins in duck farms: Concentrations, distribution, and dietary exposure risks.

Chlorinated paraffins (CPs) in poultry feed and the farm environment might bioaccumulate in poultry eggs. Unlike chickens, which are mostly raised in cages, ducks are commonly raised free range. This would expose ducks to CPs in the environment. However, information on the presence of CPs on duck farms is scarce. In the present study, samples of duck eggs, duck feathers, poultry feed, and soil were collected from 25 duck farms in South China. Forty-eight congener groups of short- and medium-chain CPs (SCCPs and MCCPs) were detected in the samples. Interestingly, relatively high concentrations of SCCPs and MCCPs were found in the duck feathers. The median concentrations of SCCPs and MCCPs in the duck eggs, feathers, feed and soil were: 46 and 18 ng/g wet weight, 2460 and 992 ng/g, 103 and 47 ng/g, and 24 and 10 ng/g dry weight, respectively. The dominant groups of SCCPs and MCCPs were C10Cl6-7 and C14Cl7-8, respectively. The close relationship between duck feathers and poultry feed indicated that the duck feathers might act as a bioindicator for the exposure of ducks to CPs. The margin of exposure approach was used to assess the health risk, with the results showing that the consumption of duck eggs posed a low risk to different age groups from exposure to SCCPs and MCCPs.

Hypoxaemia risk in pediatric flexible bronchoscopy for foreign body removal: a retrospective study.

BACKGROUND: Hypoxemia represents the most prevalent adverse event during flexible bronchoscopy procedures aimed at foreign body retrieval in pediatric patients; if not expeditiously managed, it carries the potential for cardiac or respiratory arrest. The specific risk factors contributing to the occurrence of hypoxemia during foreign body FB removal via bronchoscopy have yet to be definitively established. METHODS: This retrospective study included a cohort of 266 pediatric subjects from January 1, 2015, to December 31, 2022, who underwent flexible bronchoscopy for the purpose of FB extraction. In this cohort, the supraglottic airway was used to connect the anesthesia apparatus during the removal procedure. RESULTS: In total, 45 of the pediatric patients (16.9%) experienced episodes of hypoxemia during the FB removal procedure. Multivariate analysis revealed that the following factors were significantly associated with the occurrence of hypoxemia: an operation time exceeding 60 min (odds ratio [OR] 8.55; 95% confidence interval [CI] 3.82-19.13), a maximum diameter exceeding 7 mm (OR 5.03; 95% CI, 2.24-11.29), and the presence of radiological evidence indicating pneumonia (OR 2.69; 95% CI, 1.27-5.69). CONCLUSION: During flexible bronchoscopy procedures aimed at FB removal in pediatric patients, there is an increased susceptibility to hypoxemia. Factors including extended operation duration, larger FB dimensions, and radiographic evidence suggestive of pneumonia significantly contribute to a heightened risk of hypoxemia.

Fuzheng Huayu recipe inhibits bleomycin-induced pulmonary fibrosis in rats by inhibiting M2 polarization of macrophages via the oxidative phosphorylation pathway.

Fuzheng Huayu recipe (FZHYR) is a Chinese patent medicine for the treatment of fibrosis. The effects of FZHYR on pulmonary fibrosis and macrophage polarization were investigated in vitro. FZHYR inhibited pulmonary inflammation and fibrosis and M2 polarization of macrophages in bleomycin-induced pulmonary fibrosis (BPF) of rat model. Differentially expressed genes were screened by high-throughput mRNA sequencing and GSEA showed that oxidative phosphorylation (OXPHOS) was correlated with BPF. FZHYR inhibited expressions of Ndufa2 and Ndufa6 in lung tissues of BPF rats. These findings suggest that OXPHOS pathway serves as a possible target for pulmonary fibrosis therapy by FZHYR.

Attitude Correlated Frames Based Calibration Method for Star Sensors.

Star sensors undergo laboratory calibration before they leave the factory. In addition, recalibration is necessary after they experience vibration, deformation, etc. Using the analysis of attitude-dependent and attitude-independent interstar angular invariance calibration methods (IAICMs) as a reference, an attitude-correlated frame-based calibration method (ACFCM) is proposed in this work, which combines the advantages of both methods. Using outdoor star observations, the ACFCM correlates star image frames obtained at different times via a strapdown gyro unit. As a result, the number of efficient star images for calibration increases rapidly and the distribution of star images becomes much more uniform, thus improving the calibration accuracy of the star sensor. A simulation and experimental tests were designed and carried out. Both the simulation and experimental results verify the feasibility of the proposed ACFCM method. Furthermore, by comparing our method with the IAICMs, the repeatability and reliability of the principal point obtained from the calibration with the ACFCM method proposed in this work were significantly improved.

[Transthoracic Echocardiography Revealed Inferior Vena Cava and Right Atrial Occupation:Report of One Case].

One case with ascites and lower limb edema as the initial manifestations was reported.The echocardiography revealed inferior vena cava and right atrial occupation,which combined with increased alpha fetoprotein and imaging examination,suggested liver malignant tumor combined with tumor thrombus of inferior vena cava and right atrium.After targeted therapy combined with immunotherapy,the tumor shrank and alpha fetoprotein decreased significantly,suggesting that the treatment was effective.The median survival time of the patient was 3 months.This patient had a clear history of cirrhosis due to hepatitis B and was clinically diagnosed with advanced liver cancer,which suggested the importance of early liver cancer screening.

Research on the construction of a "full-chain" rapid response system for power emergencies.

A crucial industry for improving society's sustainable development is the power sector. To address issues with the ineffectiveness of electric power emergency response during emergencies and the unclear division of duty among emergency subjects. A prefecture-level city power supply company to respond to the "In-Fa" typhoon, for example, to build a "1 + N" two-level emergency rapid response unit. Furthermore, it is proposed from the emergency response, emergency coordination, emergency material reserves, etc., to build a "full-chain" type of power emergency quick reaction system. Case studies have revealed that the quick response system's emergency combat capability, catastrophe preventive and mitigation capability, and emergency security capability have all improved. The construction of a "full-chain" type of power emergency rapid response system specialized and standardized the power emergency response system and provided a reference basis for the power industry's emergency response.

Insight on ecDNA-mediated tumorigenesis and drug resistance.

Extrachromosomal DNAs (ecDNAs) are a pervasive feature found in cancer and contain oncogenes and their corresponding regulatory elements. Their unique structural properties allow a rapid amplification of oncogenes and alter chromatin accessibility, leading to tumorigenesis and malignant development. The uneven segregation of ecDNA during cell division enhances intercellular genetic heterogeneity, which contributes to tumor evolution that might trigger drug resistance and chemotherapy tolerance. In addition, ecDNA has the ability to integrate into or detach from chromosomal DNA, such progress results into structural alterations and genomic rearrangements within cancer cells. Recent advances in multi-omics analysis revealing the genomic and epigenetic characteristics of ecDNA are anticipated to make valuable contributions to the development of precision cancer therapy. Herein, we conclud the mechanisms of ecDNA generation and the homeostasis of its dynamic structure. In addition to the latest techniques in ecDNA research including multi-omics analysis and biochemical validation methods, we also discuss the role of ecDNA in tumor development and treatment, especially in drug resistance, and future challenges of ecDNA in cancer therapy.

[Retracted] ATP­binding cassette transporter A7 accelerates epithelial­to­mesenchymal transition in ovarian cancer cells by upregulating the transforming growth factor­ß signaling pathway.

[This retracts the article DOI: 10.3892/ol.2018.9366.].

MASA-TCN: Multi-Anchor Space-Aware Temporal Convolutional Neural Networks for Continuous and Discrete EEG Emotion Recognition.

Emotion recognition from electroencephalogram (EEG) signals is a critical domain in biomedical research with applications ranging from mental disorder regulation to human-computer interaction. In this paper, we address two fundamental aspects of EEG emotion recognition: continuous regression of emotional states and discrete classification of emotions. While classification methods have garnered significant attention, regression methods remain relatively under-explored. To bridge this gap, we introduce MASA-TCN, a novel unified model that leverages the spatial learning capabilities of Temporal Convolutional Networks (TCNs) for EEG emotion regression and classification tasks. The key innovation lies in the introduction of a space-aware temporal layer, which empowers TCN to capture spatial relationships among EEG electrodes, enhancing its ability to discern nuanced emotional states. Additionally, we design a multi-anchor block with attentive fusion, enabling the model to adaptively learn dynamic temporal dependencies within the EEG signals. Experiments on two publicly available datasets show that MASA-TCN achieves higher results than the state-of-the-art methods for both EEG emotion regression and classification tasks.

Construction of preclinical evidence for propofol in the treatment of reperfusion injury after acute myocardial infarction: A systematic review and meta-analysis.

Propofol, a commonly used intravenous anesthetic, has demonstrated potential in protecting against myocardial ischemia/reperfusion injury (MIRI) based on preclinical animal studies. However, the clinical benefits of propofol in this context are subject to debate. We conducted a systematic search across eight databases to identify all relevant animal studies investigating the preventive effects of propofol on MIRI until October 30, 2023. We assessed the methodological quality of the included studies using SYRCLE's bias risk tool. Statistical analysis was performed using STATA 15.1. The primary outcome measures analyzed in this study were myocardial infarct size (IS) and myocardial injury biomarkers. This study presents a comprehensive analysis of 48 relevant animal studies investigating propofol's preventive effects on MIRI. Propofol administration demonstrated a reduction in myocardial IS and decreased levels of myocardial injury biomarkers (CK-MB, LDH, cTnI). Moreover, propofol improved myocardial function parameters (+dp/dtmax, -dP/dtmax, LVEF, LVFS), exhibited favorable effects on inflammatory markers (IL-6, TNF-α) and oxidative stress markers (SOD, MDA), and reduced myocardial cell apoptotic index (AI). These findings suggest propofol exerts cardioprotective effects by reducing myocardial injury, decreasing infarct size, and improving heart function. However, the absence of animal models that accurately represent comorbidities such as aging and hypertension, as well as inconsistent administration methods that align with clinical practice, may hinder its clinical translation. Further robust investigations are required to validate these findings, elucidate the underlying mechanisms of propofol, and facilitate its potential translation into clinical practice.

Power Generation from the Interaction of a Carbon Foam and Water.

Understanding the interaction mechanisms between the surface of carbon-based materials and water is of great significance for the development of water-based energy storage and energy conversion devices. Herein, a self-supporting electric generator is demonstrated based on water adsorption on the surface of the carbon foam (CF) that works with various water resources, including deionized (DI) water, tap water, wastewater, and seawater. It is revealed that the dissociation of oxygen-containing groups on the surface of CF after water molecule adsorption leads to a reduction of the surface potential of the CF. Through surface modulation techniques such as reduction and oxidation, a balance has been uncovered between the oxygen content and conductivity for the high-performance CFs. The generator can generate an open-circuit voltage of approximately 0.6 V in natural seawater with a power density of up to 0.77 mW g-1. A high voltage of more than 2 V can be achieved easily by assembling components connected in series to drive electronic devices, such as a light-emitting diode (LED). This work demonstrates a simple and low-cost method for electricity harvesting, offering an additional option for self-powered devices.