The protective effects of Chromofungin in oligomeric amyloid ß42 (Aß42)-induced toxicity in neurons in Alzheimer's disease.

Oligomeric Aß42 is considered to play a harmful role in the pathophysiology of Alzheimer's disease (AD). Prolonged exposure to oligomeric Aß42 could induce neuronal damage including cellular senescence. Amelioration of Aß42-induced cellular senescence has been considered as a promising strategy for the treatment of AD. Chromofungin, a chromogranin A-derived peptide, has displayed various biological functions in different types of cells and tissues. However, the effects of Chromofungin on oligomeric Aß42-induced cellular senescence have not been previously reported. In the current study, we report a novel function of Chromofungin by showing that treatment with Chromofungin could ameliorate Aß42-induced neurotoxicity in M17 neuronal cells. The Cell Counting Kit-8 (CCK-8) assay and the lactate dehydrogenase (LDH) release experiments revealed that 0.5 and 1 mM are the optimal concentrations of Chromofungin for cell culture in M17 cells. Challenging with oligomeric Aß42 (5 µM) for 7 and 14 days led to a significant decrease in telomerase activity, which was rescued by Chromofungin dose-dependently. Additionally, the senescence-associated ß-galactosidase (SA-ß-gal) staining assay demonstrated that Chromofungin mitigated oligomeric Aß42-induced cellular senescence. Correspondingly, treatment with Chromofungin reversed the gene expression of human telomerase reverse transcriptase (hTERT), telomeric repeat-binding factor 2 (TERF2), and p21 against oligomeric Aß42 in M17 neurons. Interestingly, Chromofungin attenuated oligomeric Aß42-induced oxidative stress (OS) in M17 cells by reducing the production of intracellular reactive oxygen species (ROS) but increasing the levels of intracellular superoxide dismutase (SOD). Importantly, the presence of Chromofungin reduced the expression of cyclooxygenase2 (COX-2) as well as the generation of prostaglandin E2 (PGE2). Transduction with Ad-COX-2 impaired the effects of Chromofungin on telomerase activity and the profile of cellular senescence. Our findings suggest that Chromofungin might act as a potential agent for the treatment of AD.

HO-1 upregulation promotes mitophagy-dependent ferroptosis in PM2.5-exposed hippocampal neurons.

Fine particulate matter (PM2.5) has been extensively implicated in the pathogenesis of neurodevelopmental disorders, but the underlying mechanism remains unclear. Recent studies have revealed that PM2.5 plays a role in regulating iron metabolism and redox homeostasis in the brain, which is closely associated with ferroptosis. In this study, the role and underlying mechanism of ferroptosis in PM2.5-induced neurotoxicity were investigated in mice, primary hippocampal neurons, and HT22 cells. Our findings demonstrated that exposure to PM2.5 could induce abnormal behaviors, neuroinflammation, and neuronal loss in the hippocampus of mice. These effects may be attributed to ferroptosis induced by PM2.5 exposure in hippocampal neurons. RNA-seq analysis revealed that the upregulation of iron metabolism-related protein Heme Oxygenase 1 (HO-1) and the activation of mitophagy might play key roles in PM2.5-induced ferroptosis in HT22 cells. Subsequent in vitro experiments showed that PM2.5 exposure significantly upregulated HO-1 in primary hippocampal neurons and HT22 cells. Moreover, PM2.5 exposure activated mitophagy in HT22 cells, leading to the loss of mitochondrial membrane potential, alterations in the expression of autophagy-related proteins LC3, P62, and mTOR, as well as an increase in mitophagy-related protein PINK1 and PARKIN. As a heme-degradation enzyme, the upregulation of HO-1 promotes the release of excess iron, genetically inhibiting the upregulation of HO-1 in HT22 cells could prevent both PM2.5-induced mitophagy and ferroptosis. Furthermore, pharmacological inhibition of mitophagy in HT22 cells reduced levels of ferrous ions and lipid peroxides, thereby preventing ferroptosis. Collectively, this study demonstrates that HO-1 mediates PM2.5-induced mitophagy-dependent ferroptosis in hippocampal neurons, and inhibiting mitophagy or ferroptosis may be a key therapeutic target to ameliorate neurotoxicity following PM2.5 exposure.

Longitudinal change of intrinsic capacity and associated factors in older Chinese adults: China Health and Retirement Longitudinal Study.

BACKGROUND: Although intrinsic capacity (IC) has been constructed in older populations, whether IC retains the same structure over time has not been formally examined, nor have the factors associated with the changes in IC over time been thoroughly investigated. This study aimed to establish that the structure of IC remains unchanged over time by testing its longitudinal measurement invariance and to investigate factors that influence the longitudinal change of IC over time. METHODS: Data came from 7,271 participants aged 60 and older from the China Health and Retirement Longitudinal Study in 2011 (Wave 1) and 2015 (Wave 3). Bifactor confirmatory factor analysis (CFA) was used to construct IC with its domains, and the longitudinal measurement invariance of IC between Waves was tested. RESULTS: Bifactor CFA fitted the data well at both Waves and showed good construct validity. Partial scalar invariance was supported with non-invariant intercepts for delayed word recall, math, and close vision. Decreases in IC were associated with increasing age, being female (-0.030, 95% CI: -0.045, -0.016), living in rural areas (-0.019, 95% CI: -0.030, -0.009), BMI < 18.5 (-0.019, 95% CI: -0.035, -0.003), and hypertension (-0.012, 95% CI: -0.022, -0.001). Increases in IC were associated with higher education (primary school: 0.012, 95% CI: 0.001, 0.024; lower secondary school: 0.023, 95% CI: 0.005, 0.041) and drinking ≥4/week (0.019, 95% CI: 0.003, 0.034). Stratifying the sample by gender, the protective effect of education was observed only in women. CONCLUSIONS: The bifactor structure of the IC construct was valid and retained its meaning over time. Longitudinal changes in IC were associated with various sociodemographic factors, lifestyle, and health conditions, confirming the need to monitor IC for timely intervention, particularly in those with risk factors for IC decline.

Oxidative stress-mediated activation of FTO exacerbates impairment of the epithelial barrier by up-regulating IKBKB via N6-methyladenosine-dependent mRNA stability in asthmatic mice exposed to PM2.5.

In order to comprehend the underlying mechanisms contributing to the development and exacerbation of asthma resulting from exposure to fine particulate matter (PM2.5), we established an asthmatic model in fat mass and obesity-associated gene knockdown mice subjected to PM2.5 exposure. Histological analyses using hematoxylin-eosin (HE) and Periodic Acid-Schiff (PAS) staining revealed that the down-regulation of the fat mass and obesity-associated gene (Fto) expression significantly ameliorated the pathophysiological alterations observed in asthmatic mice exposed to PM2.5. Furthermore, the down-regulation of Fto gene expression effectively attenuated damage to the airway epithelial barrier. Additionally, employing in vivo and in vitro models, we elucidated that PM2.5 modulated FTO expression by inducing oxidative stress. Asthmatic mice exposed to PM2.5 exhibited elevated Fto expression, which correlated with increased levels of reactive oxygen species. Similarly, when cells were exposed to PM2.5, FTO expression was up-regulated in a ROS-dependent manner. Notably, the administration of N-acetyl cysteine successfully reversed the PM2.5-induced elevation in FTO expression. Concurrently, we performed transcriptome-wide Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) analysis subsequent to PM2.5 exposure. Through the implementation of Gene Set Enrichment Analysis and m6A-IP-qPCR, we successfully identified inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB) as a target gene regulated by FTO. Interestingly, exposure to PM2.5 led to increased expression of IKBKB, while m6A modification on IKBKB mRNA was reduced. Furthermore, our investigation revealed that PM2.5 also regulated IKBKB through oxidative stress. Significantly, the down-regulation of IKBKB effectively mitigated epithelial barrier damage in cells exposed to PM2.5 by modulating nuclear factor-kappa B (NF-κB) signaling. Importantly, we discovered that decreased m6A modification on IKBKB mRNA facilitated by FTO enhanced its stability, consequently resulting in up-regulation of IKBKB expression. Collectively, our findings propose a novel role for FTO in the regulation of IKBKB through m6A-dependent mRNA stability in the context of PM2.5-induced oxidative stress. Therefore, it is conceivable that the utilization of antioxidants or inhibition of FTO could represent potential therapeutic strategies for the management of asthma exacerbated by PM2.5 exposure.

Fine particulate matter 2.5 induces susceptibility to Pseudomonas aeruginosa infection via expansion of PD-L1high neutrophils in mice.

BACKGROUND: Exposure to PM2.5 has been implicated in a range of detrimental health effects, particularly affecting the respiratory system. However, the precise underlying mechanisms remain elusive. METHODS: To address this objective, we collected ambient PM2.5 and administered intranasal challenges to mice, followed by single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of neutrophils and unveil their gene expression profiles. Flow cytometry and immunofluorescence staining were subsequently conducted to validate the obtained results. Furthermore, we assessed the phagocytic potential of neutrophils upon PM2.5 exposure using gene analysis of phagocytosis signatures and bacterial uptake assays. Additionally, we utilized a mouse pneumonia model to evaluate the susceptibility of PM2.5-exposed mice to Pseudomonas aeruginosa infection. RESULTS: Our study revealed a significant increase in neutrophil recruitment within the lungs of PM2.5-exposed mice, with subclustering of neutrophils uncovering subsets with distinct gene expression profiles. Notably, exposure to PM2.5 was associated with an expansion of PD-L1high neutrophils, which exhibited impaired phagocytic function dependent upon PD-L1 expression. Furthermore, PM2.5 exposure was found to increase the susceptibility of mice to Pseudomonas aeruginosa, due in part to increased PD-L1 expression on neutrophils. Importantly, monoclonal antibody targeting of PD-L1 significantly reduced bacterial burden, dissemination, and lung inflammation in PM2.5-exposed mice upon Pseudomonas aeruginosa infection. CONCLUSIONS: Our study suggests that PM2.5 exposure promotes expansion of PD-L1high neutrophils with impaired phagocytic function in mouse lungs, contributing to increased vulnerability to bacterial infection, and therefore targeting PD-L1 may be a therapeutic strategy for reducing the harmful effects of PM2.5 exposure on the immune system.

MMP14high macrophages orchestrate progressive pulmonary fibrosis in SR-Ag-induced hypersensitivity pneumonitis.

Fibrotic hypersensitivity pneumonitis (FHP) is a fatal interstitial pulmonary disease with limited treatment options. Lung macrophages are a heterogeneous cell population that exhibit distinct subsets with divergent functions, playing pivotal roles in the progression of pulmonary fibrosis. However, the specific macrophage subpopulations and underlying mechanisms involved in the disease remain largely unexplored. In this study, a decision tree model showed that matrix metalloproteinase-14 (MMP14) had higher scores for important features in the up-regulated genes in macrophages from mice exposed to the Saccharopolyspora rectivirgula antigen (SR-Ag). Using single-cell RNA sequencing (scRNA-seq) analysis of hypersensitivity pneumonitis (HP) mice profiles, we identified MMP14high macrophage subcluster with a predominant M2 phenotype that exhibited higher activity in promoting fibroblast-to myofibroblast transition (FMT). We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag. The exosomes derived from MMP14-overexpressing macrophages were found to be more effective in regulating the transition of fibroblasts through exosomal MMP14. Importantly, it was observed that the transfer of MMP14-overexpressing macrophages into mice promoted lung inflammation and fibrosis induced by SR-Ag. NSC-405020 binding to the hemopexin domain (PEX) of MMP-14 ameliorated lung inflammation and fibrosis induced by SR-Ag in mice. Thus, MMP14-overexpressing macrophages may be an important mechanism contributing to the exacerbation of allergic reactions. Our results indicated that MMP14 in macrophages has the potential to be a therapeutic target for HP.

Research progress of the methods for predicting the efficacy of immune checkpoint inhibitors in hepatocellular carcinoma treatment / 中华肝胆外科杂志

In recent years, immune checkpoint inhibitors (ICIs) have emerged as a significant advancement in the treatment of advanced hepatocellular carcinoma (HCC), providing benefits to a subset of patients. At present, there are still many problems with ICIs treatment for HCC, such as limited objective remission rate, high treatment cost, frequent treatment-related adverse events, and tumor hyperprogression. In this context, it is important to find indicators that can predict the efficacy of ICIs treatment in order to optimize patients’ selection and maximize clinical benefits, further avoiding unnecessary toxic side effects and economic losses. This article discusses biochemical and cytological indicators, tumor-related markers, imaging indicators, and immune-related adverse events in order to guide clinical treatment.

Diagnostic Efficacy of 18F-FDG PET/CT in Detecting Bone Marrow Infiltration in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma / 生物医学与环境科学（英文）

OBJECTIVE@#Diffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL.@*METHODS@#A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and 18F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of 18F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.@*RESULTS@#The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy ( P = 0.302) or between the two bone marrow biopsies ( P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759-0.979), 0.934 (95% CI, 0.855-0.972), and 0.857, respectively.@*CONCLUSION@#18F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.

Advantages, development opportunities, and practice paths of traditional Chinese medicine in prevention and treatment of elderly comorbidities / 中国中药杂志

This article focused on the significant public health issue of comorbidities in the elderly population and highlighted the important role of traditional Chinese medicine(TCM) in the prevention and treatment of comorbidities in the elderly. It suggested that TCM should fully utilize its advantages in holistic perspective, syndrome differentiation and treatment, and preventive medicine in the process of preventing and treating comorbidities in the elderly. At the same time, in response to the significant shift in the disease spectrum of the elderly, the increasingly innovative concepts in diagnosis and treatment, the growing demand for proactive health by the el-derly population, and the current emphasis on patient-centered evaluation standards, it is necessary to further conduct basic theoretical and experimental research on comorbidities in the elderly using TCM, emphasize clinical research on comorbidities in the elderly, explore appropriate efficacy evaluation systems, improve TCM prevention and treatment strategies and comprehensive intervention programs for comorbidities in the elderly, and leverage the unique role of TCM in the rehabilitation of elderly comorbidity patients. By analyzing the potential of TCM in the field of comorbidities in the elderly, this article is expected to provide new insights for future clinical practice and scientific research.

3-(2,2,2-Trifluoroethoxy)propionitrile-based electrolytes for high energy density lithium metal batteries.

In this study, 3-(2,2,2-trifluoroethoxy)-propionitrile (FEON), a fluorinated nitrile compound with high oxidative stability, low volatility and non-flammability, is introduced as an electrolyte solvent for high-energy density Li|NCM batteries. After optimization of the electrolyte as (0.8 M LiTFSI + 0.2 M LiODFB)/FEC : FEON (1 : 3, by vol., abbreviated as FF13), the FEON-based electrolyte exhibits better cycling performance for both the lithium metal anode and 4.4 V high-voltage NCM cathode, compared with those of a commercial carbonate electrolyte of 1 M LiPF6/EC : EMC : DMC (1 : 1 : 1, by vol.). As for the FF13 electrolyte, the maximum coordination number of 3 for FEON molecules in the solvation structure is disclosed through molecular dynamics simulation combined with Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy measurements. Furthermore, the solid electrolyte interphase on the lithium metal anode is enriched with organic components and LiF, which is proposed from FEON decomposition based on density functional theory calculations and X-ray photoelectron spectroscopy analysis. All the above results demonstrate that fluorinated nitrile electrolytes constitute a promising platform for high energy density Li|NCM batteries.

Integrated analysis of single-cell and bulk RNA sequencing reveals pro-fibrotic PLA2G7high macrophages in pulmonary fibrosis.

Pulmonary fibrosis (PF) is the pathological change of end-stage interstitial lung diseases with high mortality and limited therapeutic options. Lung macrophages have distinct subsets with divergent functions, and play critical roles in the pathogenesis of PF. In this study, integrative analysis of lung single-cell and bulk RNA-seq data from patients with fibrotic hypersensitivity pneumonitis and idiopathic pulmonary fibrosis was utilized to identify particular macrophage subsets during the development of PF. We find a specific macrophage subpopulation highly expressing PLA2G7 in fibrotic lungs. We performed additional single-cell RNA-seq analysis to identify analogous macrophage population in bleomycin (BLM)-induced mouse pulmonary fibrosis models. By in vitro and in vivo experiments, we further reveal the pro-fibrotic role for this PLA2G7high macrophage subset in fibroblast-to-myofibroblast transition (FMT) during pulmonary fibrosis. PLA2G7 promotes FMT via LPC/ATX/LPA/LPA2 axis in macrophages. Moreover, PLA2G7 is regulated by STAT1, and pharmacological inhibition of PLA2G7 by Darapladib ameliorates pulmonary fibrosis in BLM-induced mice. The results of this study support the view that PLA2G7high macrophage subpopulation contributes importantly to the pathogenesis of PF, which provides a potential way for targeted therapy.

Characterizing cellular heterogeneity in fibrotic hypersensitivity pneumonitis by single-cell transcriptional analysis.

Fibrotic hypersensitivity pneumonitis (FHP) remains one of fatal interstitial pulmonary disease. Comprehensively dissecting the cellular heterogeneity of FHP paves the way for developing general gene therapeutic solutions for FHP. Here, utilizing an integrated strategy based on scRNA-seq, scTCR-seq, and bulk RNA-seq analysis of FHP profiles, we identified ten major cell types and 19 unique subtypes. FHP exhibited higher features of EMT and inflammation-promoting than normal control. In distinct subsets of lung macrophages in FHP, FN1high, PLA2G7high, and MS4A6Ahigh macrophages with predominant M2 phenotype exhibited higher activity of inflammatory responses and para-inflammation than other macrophages. KRT17high basal-like epithelial cells were significantly increased in FHP, and showed higher ability to induce EMT. We identified roles for ACTA2high, COL1A1high, and PLA2G2Ahigh fibroblasts in FHP, which were significantly related to interstitial fibrosis. NK cells and KLRG1+ effector CD8+ T cells had greater activity in inflammation-promoting. Our results provide a comprehensive portrait of cellular heterogeneity in FHP, and highlight the indispensable role of cell subpopulations in shaping the complexity and heterogeneity of FHP. These subpopulations are potentially key players for FHP pathogenesis.

MicroRNA-125b Accelerates and Promotes PML-RARa-driven Murine Acute Promyelocytic Leukemia / 生物医学与环境科学（英文）

Objective@#Most acute promyelocytic leukemia cases are characterized by the PML-RARa fusion oncogene and low white cell counts in peripheral blood.@*Methods@#Based on the frequent overexpression of miR-125-family miRNAs in acute promyelocytic leukemia, we examined the consequence of this phenomenon by using an inducible mouse model overexpressing human miR-125b.@*Results@#MiR-125b expression significantly accelerates PML-RARa-induced leukemogenesis, with the resultant induced leukemia being partially dependent on continued miR-125b overexpression. Interestingly, miR-125b expression led to low peripheral white cell counts to bone marrow blast percentage ratio, confirming the clinical observation in acute promyelocytic leukemia patients.@*Conclusion@#This study suggests that dysregulated miR-125b expression is actively involved in disease progression and pathophysiology of acute promyelocytic leukemia, indicating that targeting miR-125b may represent a new therapeutic option for acute promyelocytic leukemia.

Transcriptome-wide profiling discover: PM2.5 aggravates airway dysfunction through epithelial barrier damage regulated by Stanniocalcin 2 in an OVA-induced model.

BACKGROUND: Epidemiologic evidence suggests that PM2.5 exposure aggravates asthma, but the molecular mechanisms are not fully discovered. METHODS: Ovalbumin (OVA)-induced mice exposed to PM2.5 were constructed. Pathological staining and immunofluorescence were performed in in vivo study. Gene set enrichment analysis (GSEA) was performed to identify the pathway involved in asthma severity by using U-BIOPRED data (human bronchial biopsies) and RNA-seq data (Beas-2B cells treated with PM2.5). Lentiviruses transfection, Real-time qPCR, immunofluorescence staining and trans-epithelial electrical resistance (TEER) measurement were performed for mechanism exploration in vitro. RESULTS: PM2.5 exposure aggravated airway inflammation and mucus secretion in OVA-induced mice. Based on transcriptome analysis of mild-to-severe asthma from human bronchial biopsies, gene set enrichment analysis (GSEA) showed that up-regulated reactive oxygen species (ROS) pathway gene set and down-regulated apical junction gene set correlated with asthma severity. Consistent with the analysis of mild-to-severe asthma, after PM2.5 exposure, the ROS pathway in Beas-2B cells was up-regulated with the down-regulation of apical junction. The expression levels of genes involved in the specific gene sets were validated by using qPCR. The mRNA levels of junction genes, ZO-1, E-cadherin and Occludin, were significantly decreased in cells exposed to PM2.5. Moreover, it confirmed that inhibition of ROS recovered the expression levels of E-cadherin, Occludin and ZO-1, and ameliorated inflammation and mucus secretion in airway in OVA-induced mice exposed to PM2.5. Meanwhile, ROS level was elevated by PM2.5. By checking trans-epithelial electrical resistance (TEER) value, we also found that epithelial barrier was damaged after PM2.5 exposure. Importantly, Stanniocalcin 2 (STC2) was identified as a key gene in regulation of epithelial barrier. It showed that STC2 expression was up-regulated by PM2.5, which was recovered by NAC as well. Over-expression of STC2 could decrease the expression levels of ZO-1, Occludin and E-cadherin. Contrarily, suppression of STC2 could increase the expression levels of ZO-1, Occludin and E-cadherin reduced by PM2.5. CONCLUSIONS: By using transcriptome analysis, we revealed that STC2 played a key role in PM2.5 aggravated airway dysfunction through regulation of epithelial barrier in OVA-induced mice.

PM2.5 aggravates NQO1-induced mucus hyper-secretion through release of neutrophil extracellular traps in an asthma model.

BACKGROUND: Particulate matter of 2.5 µm or less in diameter (PM2.5) is one of the most complex pollutants in the atmospheric environment and harmful to human health. Epidemiologic evidence suggests that asthma exacerbation is associated with PM2.5 exposure. However, the molecular mechanism of PM2.5 in the development of asthma is not fully addressed. METHODS: PM2.5 was collected from Chengdu, China, and the components were analyzed. The relationship between PM2.5 exposure and asthma severity was investigated in an Ovalbumin (OVA)-induced murine model of asthma. U-BIOPRED data from public database and our own RNA-seq data were analyzed to identify the hub genes. Real-time qPCR, immunofluorescence, immunohistochemistry and pathological staining were applied for mechanism dissection in both in vitro and in vivo studies. RESULTS: In PM2.5 samples, a total of 11 elements including major elements and trace elements were identified, 14 of the 16 Polycyclic aromatic hydrocarbons (PAHs) were detected except Acenaphthene and Fluorene. PM2.5 exposure aggravated pulmonary inflammation, mucus secretion, and neutrophils infiltration in asthma model. Based on transcriptome analysis of mild-to-severe asthma dataset, it showed that mucus secretion and neutrophil degranulation correlated with asthma severity. Moreover, NAD(P)H:quinone oxidoreductase 1 (NQO1) was screened out as a hub gene whose expression positively correlated with MUC5AC expression in patient with asthma by performing joint analysis. Furthermore, in OVA-induced asthma model and in vitro assay, it also revealed that PM2.5-induced MU5AC expression was regulated by NQO1 through neutrophil extracellular traps (NETs) caused by oxidative stress. CONCLUSION: Taken together, we discovered a potential relationship between asthma severity and PM2.5 exposure. In addition, neutrophil depletion, NETs inhibition or anti-NQO1 might be novel potential therapeutic options for treatment of PM2.5-induced mucus hyper-secretion.

Comparison of Plasma Components between Frozen Plasma and Fresh Frozen Plasma / 中国实验血液学杂志

OBJECTIVE@#To compare the plasma components of frozen plasma (FP) and fresh frozen plasma (FFP).@*METHODS@#Twenty samples of FP and 20 samples of FFP from Beijing Red Cross Blood Center were randomly selected. Immediately after plasma melting, 12 plasma components including coagulation factor, fibrinolytic system and anticoagulation protein were detected, including activated partial thromboplastin time (APTT), prothrombin time (PT), coagulation factor Ⅷ (FⅧ) activity, coagulation factor Ⅴ (FⅤ) activity, fibrinogen(FIB) level, ADAMTS-13 activity, von Willebrand factor(vWF) activity, D-dimer (D-dimer, DD), fibrin degradation products (FDP), antithrombin (AT), protein C (PC), and protein S (PS). All these coagulation components between the two types of plasma were compared and analyzed.@*RESULTS@#Compared with FFP, APTT in FP was significantly prolonged(t=3.428, P0.05).@*CONCLUSION@#FP can substitute FFP in the treatment of some diseases, although it is lack of some coagulation factors and anticoagulation protein.

An integrative analysis identifying transcriptional features and key genes involved in COVID-19.

Aim: To elucidate the transcriptional characteristics of COVID-19. Materials & methods: We utilized an integrative approach to comprehensively analyze the transcriptional features of both COVID-19 patients and SARS-CoV-2 infected cells. Results: Widespread infiltration of immune cells was observed. We identified 233 genes that were codifferentially expressed in both bronchoalveolar lavage fluid and lung samples of COVID-19 patients. Functional analysis suggested upregulated genes were related to immune response such as neutrophil activation and antivirus response, while downregulated genes were associated with cell adhesion. Finally, we identified LCN2, STAT1 and UBE2L6 as core genes during SARS-CoV-2 infection. Conclusion: The identification of core genes involved in COVID-19 can provide us with more insights into the molecular features of COVID-19.

Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19.

It has been reported that SARS-CoV-2 may use ACE2 as a receptor to gain entry into human cells, in a way similar to that of SARS-CoV. Analyzing the distribution and expression level of ACE2 may therefore help reveal underlying mechanisms of viral susceptibility and post-infection modulation. In this study, we utilized previously uploaded information on ACE2 expression in various conditions including SARS-CoA to evaluate the role of ACE2 in SARS-CoV and extrapolate that to COVID-19. We found that the expression of ACE2 in healthy populations and patients with underlying diseases was not significantly different. However, based on the elevated expression of ACE2 in cigarette smokers, we speculate that long-term smoking may be a risk factor for COVID-19. Analysis of ACE2 in SARS-CoV infected cells suggests that ACE2 is not only a receptor but is also involved in post-infection regulation, including immune response, cytokine secretion, and viral genome replication. Moreover, we constructed Protein-protein interaction (PPI) networks and identified hub genes in viral activity and cytokine secretion. Our findings may help clinicians and researchers gain more insight into the pathogenesis of SARS-CoV-2 and design therapeutic strategies for COVID-19.

Nootropic effect of neferine on aluminium chloride-induced Alzheimer's disease in experimental models.

Alzheimer's disease (AD) is an age-associated neurodegenerative disease, which is developed by oxidative stress and acetylcholine contraction in the synaptic cleft of the neurons. This leads to dementia, memory loss, and decrease in learning ability and orientation. In this research work, we aimed to explore the neuroprotective effect of neferine on AlCl3 -induced AD in rats. The results of our study revealed that the increased reactive oxygen species (ROS) and nitric oxide in the hippocampus leads to the development of AD in the rats. The oral treatment of neferine done the following occurrences such as; it potentially inhibited the ROS formation and acts as a scavenging molecule by preventing the neurodegeneration. It also improved the memory and learning ability to complete the maze activity in the AD rats and significantly increased the antioxidants superoxide dismutase, catalase, and reduced glutathione in neferine treated AD rats. It aggressively declined the activity of acetylcholine esterase and Na+ K+ ATPase in the neurodegenerative rat models. The gene expression pattern of neuroinflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were decreased in the neferine-treated rats. The neuroinflammatory proteins such as inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor kappa ß (Nf-κß) were decreased and Nf-κß inhibitor IKBα was increased in the neferine-treated AD rats. Finally, the histology study proved that the neferine treatment possibly prevents neurodegeneration in the hippocampus tissue of the AD models. Hence, these all findings concluded that the neferine could be a potential neuropreventive as well as neurodegenerative therapeutic compound in neurological and cognitive dysfunction.

Effect of augmented renal clearance on plasma concentration of vancomycin and treatment outcome in children with methicillin-resistant Staphylococcus aureus infection / 中国当代儿科杂志

OBJECTIVE@#To investigate the effect of augmented renal clearance (ARC) on plasma concentration of vancomycin, bacteriological outcome, and clinical outcome in children with methicillin-resistant Staphylococcus aureus (MRSA) infection treated by vancomycin.@*METHODS@#A retrospective analysis was performed for the clinical data of 60 critically ill children who were treated with vancomycin due to MRSA infection from January 2013 to July 2017 and underwent plasma concentration monitoring. According to estimated glomerular filtration rate, these children were divided into an ARC group with 19 children and a normal renal function group with 41 children. The two groups were compared in terms of the use of vancomycin, plasma concentration of vancomycin, and treatment outcome.@*RESULTS@#The children in the ARC group had an age of 1-12 years, and the ARC group had significantly higher body weight and body surface area than the normal renal function group (P0.05), but the ARC group had significantly longer length of stay in the pediatric intensive care unit (PICU) and length of hospital stay than the normal renal function group (P<0.05).@*CONCLUSIONS@#ARC can significantly reduce the trough concentration of vancomycin and prolong the length of PICU stay and the length of hospital stay in children with MRSA infection. Idividualized medication should be administered to children with ARC.