Mecp2 promotes the anti-inflammatory effect of alpinetin via epigenetic modification crosstalk.

In recent years, inflammatory disorders have emerged as a significant concern for human health. Through ongoing research on anti-inflammatory agents, alpinetin has shown promising anti-inflammatory properties, including involvement in epigenetic modification pathways. As a crucial regulator of epigenetic modifications, Mecp2 may play a role in modulating the epigenetic effects of alpinetin, potentially impacting its anti-inflammatory properties. To test this hypothesis, two key components, p65 (a member of NF-KB family) and p300 (a type of co-activator), were screened by the expression profiling microarray, which exhibited a strong correlation with the intensity of LPS stimulation in mouse macrophages. Meanwhile, alpinetin demonstrates the anti-inflammatory properties through its ability to disrupt the synthesis of p65 and its interaction with promoters of inflammatory genes, yet it did not exhibit similar effects on p300. Additionally, Mecp2 can inhibit the binding of p300 by attaching to the methylated inflammatory gene promoter induced by alpinetin, leading to obstacles in promoter acetylation and subsequently impacting the binding of p65, ultimately enhancing the anti-inflammatory capabilities of alpinetin. Similarly, in a sepsis mouse model, it was observed that homozygotes overexpressing Mecp2 showed a greater reduction in organ damage and improved survival rates compared to heterozygotes when administered by alpinetin. However, blocking the expression of DNA methyltransferase 3A (DNMT3A) resulted in the loss of Mecp2's anti-inflammatory assistance. In conclusion, Mecp2 may augment the anti-inflammatory effects of alpinetin through epigenetic 'crosstalk', highlighting the potential efficacy of a combined therapeutic strategy involving Mecp2 and alpinetin for anti-inflammatory intervention.

A machine learning model for predicting acute exacerbation of in-home chronic obstructive pulmonary disease patients.

PURPOSE: This study utilized intelligent devices to remotely monitor patients with chronic obstructive pulmonary disease (COPD), aiming to construct and evaluate machine learning (ML) models that predict the probability of acute exacerbations of COPD (AECOPD). METHODS: Patients diagnosed with COPD Group C/D at our hospital between March 2019 and June 2021 were enrolled in this study. The diagnosis of COPD Group C/D and AECOPD was based on the GOLD 2018 guidelines. We developed a series of machine learning (ML)-based models, including XGBoost, LightGBM, and CatBoost, to predict AECOPD events. These models utilized data collected from portable spirometers and electronic stethoscopes within a five-day time window. The area under the ROC curve (AUC) was used to assess the effectiveness of the models. RESULTS: A total of 66 patients were enrolled in COPD groups C/D, with 32 in group C and 34 in group D. Using observational data within a five-day time window, the ML models effectively predict AECOPD events, achieving high AUC scores. Among these models, the CatBoost model exhibited superior performance, boasting the highest AUC score (0.9721, 95 % CI: 0.9623-0.9810). Notably, the boosting tree methods significantly outperformed the time-series based methods, thanks to our feature engineering efforts. A post-hoc analysis of the CatBoost model reveals that features extracted from the electronic stethoscope (e.g., max/min vibration energy) hold more importance than those from the portable spirometer. CONCLUSIONS: The tree-based boosting models prove to be effective in predicting AECOPD events in our study. Consequently, these models have the potential to enhance remote monitoring, enable early risk assessment, and inform treatment decisions for homebound patients with chronic COPD.

Exploring the Impact of Blend and Graft of Quinoline Derivative in Low-Temperature Curable Polyimides.

The utilization of accelerators has been a common approach to prepare low-temperature curable polyimide (PI). However, the accelerators have gradually fallen out of favor because of their excessive dosages and negative effect on the properties of PI. In this work, a new strategy of introducing accelerators by grafting to eliminate these disadvantages is presented. A novel quinoline derivative named 6-([1,1'-biphenyl]-4-yl)-4-chloroquinoline (NQL) is designed for this purpose, and an ultralow dosage of only 2.5 mol% is sufficient to prepare low-temperature curable PI. The favorable low-temperature curing effect of NQL is attributed to its strong alkalinity (pKa = 18.47) and electron-donating ability. At a curing temperature of 200 °C, the PI with 2.5 mol% NQL showed outstanding properties (Young's modulus of 5.73 GPa, elongation of 37.3%, tensile strength of 237 MPa, and coefficient of thermal expansion of 16 ppm K-1 ). In particular, NQL can even lower the curing temperature to 180 °C and the ultralow temperature curable PI film still retains excellent properties. These results demonstrate that introducing low-temperature curable accelerators by partial grafting instead of blending is a promising way to furnish low-temperature curable PI, and provide insights into the preparation of polyimide with high performance in advanced packaging.

Protective Effect of Galangin Methylation Modification Based on Cell Imaging on Inflammatory Lung Injury and Its Molecular Mechanism.

Background: Recently, inflammation has become a major threat to human health. Studies have confirmed that some Chinese traditional medicine ingredients may effectively interfere with the expression of inflammatory mediators through epigenetic modification, showing a great potential of the application. Objective: To investigate the role of the PPAR/DNMT3A pathway in the reversal of galangin-mediated inflammatory lung injury, promote the development of new anti-inflammatory drugs, reduce the side effects of chemical synthetic drugs on the body, and prove the effectiveness and safety of galangin in inhibiting inflammatory response and injury. Methods: 120 rats were randomly divided into 6 groups: (Group 1) LPS group; (Group 2) LPS + galangin group; (Group 3) LPS + galangin + GW9662 group; (Group 4) LPS + galangin + DNMT3A siRNA group; (Group 5) LPS + galangin + siRNA negative group; (Group 6) control group. The model of inflammatory lung injury was established by intrathecal instillation of LPS in the first five groups and NS in the control group. SD survival rate was recorded every 24 hours after modeling, lasting for 168 hours. The lung tissues were taken 168 hours after the establishment of the model. The pathological morphology of lung tissue was observed after the staining under the light microscope, and the lung dry/wet weight ratio was calculated after drying. After NS was perfused into lung tissue, the lavage fluid was collected and the levels of IL-6 and TNF-a were measured by ELISA. The contents of PPAR, DNMT3A, phosphorylated p65, and ERK in monocytes were detected by the WB method, and the binding contents of p65 and AP-1 in the promoter regions of IL-6 and TNF-a genes were detected by the Chip-qPCR method. Results: Intraperitoneal injection of galangin could inhibit the synthesis of alveolar inflammatory factors (TFs) in the SD model of lung injury induced by LPS, reduce the degree of pathological injury of lung tissue, and improve the survival rate of the SD model. GW9662 can completely reverse the protective effect, while DNMT3A interference can only partially block its protective effect. In addition, galangin could significantly inhibit the LPS-induced expression of p65 and AP-1 in alveolar monocytes and their binding content in the promoter region of inflammatory genes by activating PPAR/DNMT3A pathway. GW9662 could completely reverse the inhibitory effect of galangin. DNMT3A interference could restore the binding content of transcription factors at the promoter of the inflammatory gene but had no significant effect on its synthesis. Conclusion: Galangin can interfere with the binding of transcription factors to inflammatory gene promoters through the methylation modification induced by PPAR/DNMT3A pathway, so as to inhibit the synthesis of inflammatory molecules and reverse inflammatory lung injury.

Au-Stabilized Nanoporous PdCuAu Alloys Exhibiting Outstanding Catalytic Activity and Durability for the Formic Acid Oxidation Reaction.

Metallic Pd is widely recognized as an efficient electrocatalyst for the formic acid oxidation reaction (FAOR), which unfortunately suffers from poor durability owing to Pd dissolution and CO poisoning. The present work describes an effective method to enhance Pd durability by alloying with Cu and Au. Cu could provide surface OH at low potentials to remove poisonous CO for improved CO resistance. Au, the most inert metal, was added to reduce Pd and Cu dissolution. Moreover, alloying with Cu and Au could also modulate the electronic structure of Pd which is just profitable for the FAOR. The constructed PdCuAu with a nanoporous structure exhibits a specific activity of 14.9 mA cm-2 and a Pd mass activity of 6012 A g-1, which is ∼15 times and ∼14 times higher than those of commercial Pd/C. While these two electrocatalysts were used as fuel cell anodes, the maximum power density of the PdCuAu anode (Pd loading 10 µg cm-2) is 93.2 mW cm-2 and the value of the Pd/C anode (Pd loading 1.2 mg cm-2) is 60.3 mW cm-2. The power efficiency of Pd has been notably increased by 185 times in this home-made nanoporous PdCuAu ternary alloy electrocatalyst.

Clinical Characteristics of Chlamydia psittaci Pneumonia Infection in Central South China.

INTRODUCTION: Chlamydia psittaci pneumonia has been a global public health hotspot in recent years. Although some scattered cases of C. psittaci pneumonia have been reported, there is a lack of large case studies worldwide. METHODS: In this multicenter, observational study, we recruited all consecutive patients with confirmed C. psittaci pneumonia from October 4, 2018, to October 23, 2020, in nine tertiary general hospitals in Central-South China. Epidemiologic and clinical data from patients' electronic medical records were collected and analyzed. RESULTS: One hundred and sixteen patients with C. psittaci pneumonia were included in the study. The mean age was 59.7 years. Fever (96.6%) and cough (65.5%) were the most common clinical symptoms. Most patients presented with an increase in the proportion of neutrophils, neutrophil to lymphocyte ratio, LDH, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and a significant decrease in lymphocytes. The main CT lung findings were consolidation (81%) and pleural effusion (35.3%), and bilateral lung consolidation was mainly found in severe patients. Chlamydia psittaci DNA was detected in BALF (bronchoalveolar lavage fluid) or blood samples by metagenomic next-generation sequencing (mNGS) in all patients. Use of quinolone was associated with shorter length of hospital stay and fever duration after antibiotic use. Multivariate logistic regression analysis indicated that respiratory support was associated with both severe pneumonia and in-hospital death. CONCLUSIONS: The clinical phenotype of C. psittaci pneumonia is complex and variable. mNGS is helpful in the diagnosis and treatment of C. psittaci pneumonia, and early treatment with quinolone may benefit patients.

Drain-site hernia after laparoscopic rectal resection: A case report and review of literature.

BACKGROUND: Drain-site hernia (DSH) has an extremely low morbidity and has rarely been reported. Small bowel obstruction is a frequent concurrent condition in most cases of DSH, which commonly occurs at the ≥ 10 mm drain-site. Here we report a rare case of DSH at the lateral 5 mm port site one month postoperatively without visceral incarceration. Simultaneously, a brief review of the literature was conducted focusing on the risk factors, diagnosis, and prevention strategies for DSH. CASE SUMMARY: A 76-year-old male patient was admitted to our institution with intermittent abdominal pain and a local abdominal mass which occurred one month after laparoscopic radical resection of rectal cancer one year ago. A computed tomography scan showed an abdominal wall hernia at the 5 mm former drain-site in the left lower quadrant, and that the content consisted of the large omentum. An elective herniorrhaphy was performed by closing the fascial defect and reinforcing the abdominal wall with a synthetic mesh simultaneously. The postoperative period was uneventful. The patient was discharged seven days after the operation without surgery-related complications at the 1-mo follow-up visit. CONCLUSION: Emphasis should be placed on DSH despite the decreased use of intra-abdominal drainage. It is recommended that placement of a surgical drainage tube at the ≥ 10 mm trocar site should be avoided. Moreover, it is advisable to have a comprehensive understanding of the risk factors for DSH and complete closure of the fascial defect at the drainage site for high-risk patients.

[Methyl CpG-binding protein 2 (MeCP2) inhibits the activity of methylated IL-6 promoter of HEK293 cells and its molecular mechanism].

Objective To investigate the underlying molecular mechanism of methyl-CpG-binding protein 2 (MeCP2) inhibiting interleukin 6 (IL-6) transcriptional activity by observing the sequence of methylated IL-6 promoter, overexpression of MeCP2, and transcription factor P300 in HEK293 cells. Methods The binding site of P300 in the IL-6 promoter region was confirmed by electrophoretic mobility shift assay (EMSA); the IL-6 promoter sequence was ligated into luciferase reporter plasmid and transfected into HEK293 cells. The methylation of the promoter was mediated by clustered regularly interspaced short palindromic repeats-deactivated Cas9 (CRISPR-dCas9)-mediated DNA methyltransferase 3A (DNMT3A) transfection, and then MeCP2 and P300 overexpression plasmids were transfected. The bisulfate sequencing PCR(BSP)was used to analyze the cytosine methylation in the IL-6 promoter region of each group. The contents of intracellular MeCP2 and P300 were detected by the Western blot. A chemiluminescence detector was used to determine the luciferase activity of HEK293 cells. The binding level of P300 and MeCP2 in the IL-6 promoter region was analyzed by chromatin immunoprecipitation followed by sequencing(ChIP-seq). Results EMSA confirmed the presence of P300 binding sites in the IL-6 promoter of mice. CRISPR-dCas9-DNMT3A transfection into HEK293 cells successfully methylated the IL-6 promoter. MeCP2 and P300 overexpression plasmid steadfastly synthesized the target protein and was not affected by other transfection. Compared with the unmodified promoter, methylation could reduce the transcriptional activity of the promoter. When P300 was overexpressed, MeCP2 could further inhibit the transcriptional activity of the promoter, when compared with methylation alone. Also, overexpression of P300 could not promote the transcriptional activity of IL-6 promoter after the methylation modified promoter combined with MeCP2, while the overexpression of P300 enhanced the transcriptional activity when the promoter was not methylated or MeCP2 was not overexpressed. ChIP-seq analysis revealed that the methylated IL-6 promoter showed no difference in binding to P300; however, when combined with MeCP2, the binding capacity would be repressed. Conclusion The combination of MeCP2 with methylated IL-6 promoter can inhibit the binding of the transcription factor to the promoter, thereby impeding the transcriptional activity of the promoter.

Accelerated Hydrogen "Spill-Over" Enhances Anode Performance of Tensile Strained Pd-Based Fuel Cell Electrocatalysts.

Development of efficient electrocatalysts usually relies on half-cell electrochemical tests for rapid material screening, which however are not always consistent with the associated full cell evaluation. This study designs a tensile-strained Pd anode and reveals that with a lower apparent activity toward the hydrogen oxidation reaction as compared to the unstrained one, it exhibits a surprisingly high activity in proton exchange membrane fuel cells (PEMFCs). With an ultralow Pd loading of 4.5 µg cm-2 , the tensile-strained Pd achieves a maximum power density of 1048 mW cm-2 , indicating a 30-fold improvement in power efficiency than that of commercial Pd/C, nearly four times of that of the unstrained one. This discrepancy can be ascribed to the hydrogen-rich surface in the H2 atmosphere of PEMFCs owing to the accelerated hydrogen "spill-over" in the tensile-strained Pd with a standout hydrogen storage property.

Virtual Experiments of Particle Mixing Process with the SPH-DEM Model.

Particle mixing process is critical for the design and quality control of concrete and composite production. This paper develops an algorithm to simulate the high-shear mixing process of a granular flow containing a high proportion of solid particles mixed in a liquid. DEM is employed to simulate solid particle interactions; whereas SPH is implemented to simulate the liquid particles. The two-way coupling force between SPH and DEM particles is used to evaluate the solid-liquid interaction of a multi-phase flow. Using Darcy's Law, this paper evaluates the coupling force as a function of local mixture porosity. After the model is verified by two benchmark case studies, i.e., a solid particle moving in a liquid and fluid flowing through a porous medium, this method is applied to a high shear mixing problem of two types of solid particles mixed in a viscous liquid by a four-bladed mixer. A homogeneity metric is introduced to characterize the mixing quality of the particulate mixture. The virtual experiments with the present algorithm show that adding more liquid or increasing liquid viscosity slows down the mixing process for a high solid load mix. Although the solid particles can be mixed well eventually, the liquid distribution is not homogeneous, especially when the viscosity of liquid is low. The present SPH-DEM model is versatile and suitable for virtual experiments of particle mixing process with different blades, solid particle densities and sizes, and liquid binders, and thus can expedite the design and development of concrete materials and particulate composites.

Effect of CRRT combined with low-flow ECMO on canines with ARDS and hypercapnia.

To observe the effect of continuous renal replacement therapy (CRRT) combined with low-flow extracorporeal membrane oxygenation (ECMO) of V-V mode on anti-inflammation, improving oxygenation and reducing PaCO2 in canines with acute respiratory distress syndrome (ARDS) and hypercapnia. A total of 30 healthy adult canines were randomly divided into sham group (n = 10), ECMO (EC) group (n = 10) and CRRT + ECMO (CR + EC) group (n = 10). Sham group was only treated with invasive mechanical ventilation. EC group was also treated with ECMO. CR + EC group was treated with CRRT combined with low-flow ECMO of V-V mode besides invasive mechanical ventilation. The results showed that hazard ratio was lower in the CR + EC group. Inflammatory factors, OI values, and PaCO2 levels were lower in the CR + EC group. There was no significant difference in the levels of MAP, CO and T among the three groups. No significant complications or death was developed in the three groups. Compared with ECMO group at T3, T6 and T9, IL-6 [(276.13 ± 8.32, 262.04 ± 7.15, 259.33 ± 7.31)ng/L VS (352.67 ± 19.24, 360.24 ± 23.58, 362.21 ± 25.24)ng/L] and TNF-α [(50.14 ± 1.75, 50.45 ± 1.81, 48.03 ± 1.24) ng/L VS (70.25 ± 3.02, 72.45 ± 3.25, 76.69 ± 2.18)ng/L] in CR + EC group were decreased (P < 0.0001). Compared with sham group, IL-6 [(343.76 ± 21.97, 345.91 ± 19.89, 340.34 ± 22.17)ng/L]and TNF-α [(68.10 ± 2.96, 67.31 ± 3.01, 70.34 ± 3.35)ng/L] of T3, T6 and T9 in CR + EC group were lower (P < 0.0001). These findings indicated that CRRT combined with low-flow ECMO of V-V mode had a positive effect on anti-inflammation, oxygenation improvement and surplus blood CO2 removal in canines with ARDS and hypercapnia. These results provide a promising treatment regimen for ARDS.

Prognostic Signatures Based on Ferroptosis- and Immune-Related Genes for Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are among the most common malignancies of the female genital tract. Ferroptosis and immunity regulate each other and play important roles in the progression of CESC. The present study aimed to screen ferroptosis- and immune-related differentially expressed genes (FI-DEGs) to identify suitable prognostic signatures for patients with CESC. We downloaded the RNAseq count data and corresponding clinical information of CESC patients from The Cancer Genome Atlas database; obtained recognized ferroptosis- and immune-related genes from the FerrDb and ImmPort databases, respectively; and screened for suitable prognostic signatures using a series of bioinformatics analyses. We identified eight FI-DEGs (CALCRL, CHIT1, DES, DUOX1, FLT1, HELLS, SCD, and SDC1) that were independently correlated with the overall survival of patients with CESC. The prediction model constructed using these eight FI-DEGs was also independently correlated with overall survival. Both the sensitivity and specificity of the prediction model constructed using these eight signatures were over 60%. The comprehensive index of ferroptosis and immune status was significantly correlated with the immunity of patients with CESC. In conclusion, the risk assessment model constructed with these eight FI-DEGs predicted the CESC outcomes. Therefore, these eight FI-DEGs could serve as prognostic signatures for CESC.

Room-temperature preparation of TiO2/graphene composite photoanodes for efficient dye-sensitized solar cells.

Semi-transparent TiO2/graphene photoanodes are prepared at room temperature via an electrophoretic deposition method followed by compression and applied in dye-sensitized solar cells (DSSCs). Compression enhances the power conversion efficiency (PCE) of a DSSC, which constitutes up 18.4 times improvement compared to the uncompressed device. Incorporating graphene into the compressed film further improves the PCE by 28.8%. Simultaneously, compressing and graphene incorporating can greatly increase the film's transmittance at long wavelengths, benefiting to the use of DSSCs as front unit in tandem solar cells. Scanning electron microscopy, porosity measurements, electrochemical impedance spectroscopy and open circuit voltage decay are performed to investigate the mechanisms. It is demonstrated that compressing a film can reduce the porosity and improve the inter-particle connections, which accounts for the increased light transmittance and enhanced PCE. The incorporated graphene can provide extra charge carrier pathway due to its excellent charge transport properties, as well as protect TiO2 nanostructure by preventing film cracking upon pressing due to its good flexibility, thus increases PCE to 6.75%, which, to our best knowledge, is the highest value among DSSCs with room-temperature prepared photoanodes.

Clinical characteristics and viral shedding kinetics of 38 asymptomatic patients with coronavirus disease 2019: A retrospective observational study.

ABSTRACT: This study aims to investigate the clinical characteristics and viral shedding kinetics of asymptomatic patients with coronavirus disease 2019 (COVID-19).The data of 38 asymptomatic patients positive for SARS-CoV-2 nucleic acid were collected from February to March 2020 in Tuanfeng County, Huanggang, Hubei, China. The epidemiology, laboratory examination, chest imaging, viral nucleic acid test results, clinical characteristics, and viral shedding time were summarized in this retrospective study.The study included 20 family members of patients with COVID-19, 10 medical personnel participating in COVID-19 treatment or working in a fever clinic, 6 personnel from quarantine places, 1 individual with a close contact history with confirmed patients, and 1 local epidemic prevention personnel. All were positive for SARS-CoV-2 nucleic acid. The white blood cell (WBC) count, the absolute value of lymphocytes, C-reactive protein (CRP), and D-dimer were normal. Pneumonia manifestations were not found in the chest computed tomography (CT) scan of 36 patients; the remaining 2 cases included a 1-year-old child and a pregnant woman, and they did not undergo chest CT. The viral shedding time was 6 days.All asymptomatic patients with COVID-19 had a history of close contact or exposure. Laboratory tests were normal. Chest imaging did not show any pneumonia manifestation. The viral shedding time was <10 days, which is shorter than that of patients with COVID-19. A timely discovery of such asymptomatic infections is crucial for blocking the spread of the virus and strengthening the prevention and control measures.

Toward Multi-Functional Road Surface Design with the Nanocomposite Coating of Carbon Nanotube Modified Polyurethane: Lab-Scale Experiments.

A novel multi-functional road surface system is designed to improve safety, the efficiency of traffic flow, and environmental sustainability for future transportation systems. The surface coating, preforming temperature detection with heating element and hydrophobic features, were fabricated with a nanocomposite consisting of carbon nanotube (CNT) modified polyurethane (PU). The CNT/PU coating showed higher electrical conductivity as well as enhanced hydrophobic properties as the CNT concentration increased. The multifunctional properties of CNT/PU coatings were investigated for use in freezing temperature sensing and heating. The CNT/PU coatings showed high temperature sensitivity in the freezing temperature range with a negative temperature coefficient of resistance. In addition, the CNT/PU coatings had excellent heating performance due to the Joule heating effect. Therefore, the proposed CNT/PU coatings are promising for use as multifunctional road coating materials for detection of freezing temperature and deicing by self-heating.

Environmental impacts of reclaimed asphalt pavement on leaching of metals into groundwater.

To investigate the environmental impacts of reclaimed asphalt pavement (RAP) while it was freshly processed (i.e. hot mixed asphalt or HMA) and after being subjected to weathering, three RAP materials, namely north-RAP, central-RAP, south-RAP, from three plants and one fresh HMA loose mix samples (Fresh-HMA) throughout New Jersey, USA underwent four different weathering processes including: UV and precipitation weathering on unbounded RAP, UV and precipitation weathering on compacted RAP, weathering by heat and moisture cycles, and groundwater flow-through leaching. Batch experiments were conducted to mimic releasing of trace elements in weak acidic leachate from landfills. North-RAP and central-RAP released levels of Pb greater than the United States Environmental Protection Agency (USEPA) primary drinking water maximum contaminant level (MCL) of 15 µg/L. Novel two-column experiments (a RAP column followed by a soil column) were conducted to investigate the release of trace elements from RAP and the attenuation effect of soil on potential pollutants. The results of these experiments showed that pollutants released from RAPs such as Mn and Ni were largely attenuated in the soil. The results suggest that RAP can be used as an unbound material in environments except those acidic (i.e., pH < 5 as in mines with sulfur-containing minerals and landfills with acidic environment).

Clinical characteristics and chest CT imaging features of critically ill COVID-19 patients.

OBJECTIVES: To compare clinical, laboratory, and chest computed tomography (CT) findings in critically ill patients diagnosed with coronavirus disease 2019 (COVID-19) who survived and who died. METHODS: This retrospective study reviewed 60 critically ill patients (43 males and 17 females, mean age 64.4 ± 11.0 years) with COVID-19 pneumonia who were admitted to two different clinical centers. Their clinical and medical records were analyzed, and the chest CT images were assessed to determine the involvement of lobes and the distribution of lesions in the lungs between the patients who recovered from the illness and those who died. RESULTS: Compared with recovered patients (50/60, 83%), deceased patients (10/60, 17%) were older (mean age, 70.6 vs. 62.6 years, p = 0.044). C-reactive protein (CRP) (110.8 ± 26.3 mg/L vs 63.0 ± 50.4 mg/L, p < 0.001) and neutrophil-to-lymphocyte ratio (NLR) (18.7 ± 16.6 vs 8.4 ± 7.5, p = 0.030) were significantly elevated in the deceased as opposed to the recovered. Medial or parahilar area involvement was observed in all the deceased patients (10/10, 100%), when compared to only 54% (27/50) in the recovered. Ground-glass opacities (97%), crazy-paving pattern (92%), and air bronchogram (93%) were the most common radiological findings. There was significant difference in diabetes (p = 0.025) and emphysema (p = 0.013), and the odds ratio on a deceased patient having diabetes and emphysema was 6 times and 21 times the odds ratio on a recovered patient having diabetes and emphysema, respectively. CONCLUSIONS: Older patients with comorbidities such as diabetes and emphysema, and higher CRP and NLRs with diffuse lung involvement were more likely to die of COVID-19. KEY POINTS: • Almost all patients critically ill with COVID-19 pneumonia had five lung lobes involved. • Medial or parahilar area involvement and degree of lung involvement were more serious in the deceased patients when compared with those who recovered from treatment. • Chronic lung disease, e.g., emphysema, diabetes, and higher serum CRP and NLR characterized patients who died of COVID-19.

Inhibitory effect of alpinetin on IL-6 expression by promoting cytosine methylation in CpG islands in the IL-6 promoter region.

BACKGROUND: Alpinetin is a flavonoid which exerts antibacterial and anti-inflammatory functions. In order to prove that the induced methylation is an important mechanism for alpinetin in regulating the expression of inflammatory factor Interleukin-6 (IL-6), we detected the dinucleotide methylation status of CpG islands in the IL-6 promoter region and IL-6 level after treatment of RAW246.7 murine macrophages with alpinetin. METHODS: After RAW246.7 murine macrophages were treated with alpinetin, alpinetin + GW9662 (the peroxisome proliferator-activated receptor (PPAR) antagonist), and alpinetin + DNA methyltransferase 3 alpha (DNMT3A) siRNA for 96 hr, CpG islands were analyzed using time-of-flight mass spectrophotometry (TOF-MS) and bisulfite sequencing polymerase chain reaction (BSP). Dinucleotide methylation status of the CpG islands in the IL-6 promoter region was analyzed by methylation-specific Polymerase Chain Reaction (PCR). IL-6 level was detected using the enzyme-linked immunosorbent assay (ELISA) method. Pearson's correlation analysis was conducted to test for potential correlation between the methylation status of CpG islands in the IL-6 promoter region and IL-6 level in RAW 246.7 cells. RESULTS: Alpinetin promoted dinucleotide methylation status of two CpG islands in the IL-6 promoter region stretching 500-2500 bp upstream of the transcriptional start site (TSS) (p < .05). This promoting effect was more significant for the CpG island stretching 500-1500 bp long. The methylation ratio of dinucleotide at this position was significantly inversely correlated with the level of IL-6 (p < .05). PPAR antagonist GW9662 and interference of DNMT3A could reverse both the alpinetin-induced methylation and inhibitory effects on IL-6 expression. CONCLUSION: Alpinetin could induce dinucleotide methylation status of CpG islands in the IL-6 promoter region by activating methyltransferase, thus inhibiting IL-6 expression in murine macrophages.

[miR-27a-3p inhibits pulmonary fibrosis by blocking Wnt3a/ß-catenin pathway in rats].

Objective To observe the effect of miR-27a-3p on bleomycin A5-induced pulmonary fibrosis (PF) in rats and explore the underlying mechanism. Methods Forty-five male SD rats were randomly divided into control group, miR-27a-3p agomir group and miR-27a-3p antagomir group. Each group contained 15 animals. All rats were injected intratracheally with bleomycin A5 to establish PF models. On the first day after bleomycin A5 administration, the rats in the control group, miR-27a-3p agomir group and miR-27a-3p antagomir group were injected at the caudal vein with physiological saline, agomir and antagomir, respectively. Injection was given one time each three days, totally nine times. On day 28, blood samples were collected and then underwent enzyme linked immunosorbent assay for procollagen type 1 carboxyterminal propeptide (P1CP) and procollagen type 3 aminoterminal propeptide (P3NP) concentrations. Subsequently, all rats were sacrificed to remove pulmonary tissue. Both HE and Masson staining were performed to evaluate the pathological changes of PF. The expression of miR-27a-3p, collagen type 1 (Col1), and collagen type 3 (Col3) were detected using fluorescence real time quantitative PCR. Western blotting was used to examine Col1, Col3, Wnt3a and ß-catenin levels. Results The miR-27a-3p agomir markedly increased miR-27a-3p expression in the pulmonary tissue, whereas its antagomir decreased it, showing higher transfection efficacy. The pulmonary inflammation and fibrosis degree was alleviated in the miR-27a-3p agomir group while aggravated in the miR-27a-3p antagomir group. In comparison with control group, serum P1CP and P3NP levels decreased in the miR-27a-3p agomir group but increased in the miR-27a-3p antagomir group. Treatment with miR-27a-3p agomir down-regulated the expression of Col1, Col3, Wnt3a and ß-catenin in the pulmonary tissue, while miR-27a-3p antagomir up-regulated their expression. Conclusion The miR-27a-3p inhibits the Wnt3a/ß-catenin signaling pathway, leading to the down-regulation of Col1 and Col3 expression and the subsequent alleviation of PF.

Rechargeable Al-CO2 Batteries for Reversible Utilization of CO2.

The excessive emission of CO2 and the energy crisis are two major issues facing humanity. Thus, the electrochemical reduction of CO2 and its utilization in metal-CO2 batteries have attracted wide attention because the batteries can simultaneously accelerate CO2 fixation/utilization and energy storage/release. Here, rechargeable Al-CO2 batteries are proposed and realized, which use chemically stable Al as the anode. The batteries display small discharge/charge voltage gaps down to 0.091 V and high energy efficiencies up to 87.7%, indicating an efficient battery performance. Their chemical reaction mechanism to produce the performance is revealed to be 4Al + 9CO2 ↔ 2Al2 (CO3 )3 + 3C, by which CO2 is reversibly utilized. These batteries are envisaged to effectively and safely serve as a potential CO2 fixation/utilization strategy with stable Al.