Diagnostic value of DNA or RNA-based metagenomic next-generation sequencing in lower respiratory tract infections.

Objectives: We aimed to evaluate and compare the diagnostic performance of RNA-mNGS and DNA-mNGS workflow in bacterial pneumonia, fungal pneumonia and tuberculosis. Methods: A total of 134 cases suspected pneumonia undergoing both DNA and RNA based mNGS of bronchoalveolar lavage fluid (BALF) and also traditional etiological examination were evaluated retrospectively.Sensitivity, specificity, PPV, NPV and accuracy rate of DNA and RNA based mNGS were estimated. Results: In the diagnosis performance of bacterial pathogens in LRTIs,the specificity of RNA-mNGS was higher than that of DNA-mNGS(82.3 % vs. 61.9 %, P < 0.01). There was no significant difference of sensitivity between the two process(71.4 % vs. 85.7 %, P = 0.375).In the diagnosis performance of fungal pathogens in LRTIs,the specificity of RNA-mNGS was higher than that of DNA-mNGS (72.3 % vs. 27.3 %,p < 0.001). There was no significant difference of sensitivity between the two process(96.5 % vs. 98.8 %,p = 0.125).In the diagnosis performance of tuberculosis in LRTIs,the sensitivity of DNA-mNGS was higher than that of RNA-mNGS (91.7 % vs. 33.3 %,p = 0.016),the specificity was similar in the two process (100 %). Conclusions: RNA-mNGS may reduced the misdiagnosis rate of bacterial and fungal pathogens in LRTIs.Compared to RNA-mNGS, DNA-mNGS may could improve the diagnostic rate of tuberculosis.

Potassium-Hydrogen Hybrid Ion Alkaline Battery: A New Rechargeable Aqueous Battery Combined a K+ Storage Cathode and an Electrochemical Hydrogen Storage Anode.

A rechargeable aqueous hybrid ion alkaline battery, using a proton and a potassium ion as charge carriers for the anode and cathode, respectively, is proposed in this study by using well-developed potassium nickel hexacyanoferrate as the cathode material and mesoporous carbon sheets as the anode material, respectively. The constructed battery operates in a concentrated KOH solution, in which the energy storage mechanism for potassium nickel hexacyanoferrate involves the redox reaction of Fe2+/Fe3+ associated with potassium ion insertion/extraction and the redox reaction of Ni(OH)2/NiOOH. The mechanism for the carbon anode is electrochemical hydrogen storage. The cathode made of potassium nickel hexacyanoferrate exhibits both an ultrahigh capacity of 232.7 mAh g-1 under 100 mA g-1 and a consistent performance of 214 mAh g-1 at 2000 mA g-1 (with a capacity retention of 92.8% after 200 cycles). The mesoporous carbon sheet anode exhibits a capacity of 87.6 mAh·g-1 at 100 mA g-1 with a good rate and cyclic performance. The full cell provides an operational voltage of 1.55 V, a capacity of 93.6 mAh g-1 at 100 mA g-1, and 82.4% capacity retention after 1000 cycles at 2000 mA g-1 along with a low self-discharge rate. The investigation and discussion about the energy storage mechanisms for both electrode materials are also provided.

Near-infrared-guided NO generator for combined NO/photothermal/chemodynamic therapy of bacterial infections.

Nitric oxide (NO)-based gas therapy approaches are promising in the treatment of infections; however, these strategies are hindered by poor delivery to the target site, which leads to unsatisfactory effects. In this study, we developed a NO-controlled platform (SCM@HA) via NO-generating mesoporous silica nanoparticles co-doped with sodium nitroprusside and copper sulphide to control NO production under near-infrared (NIR)-laser irradiation. Irradiation with an 808 nm NIR laser rapidly triggered the release of NO from the particles to actualise gas therapy. Photothermal therapy (PTT) also increased the local microenvironment temperature, and the close relationship between chemodynamic therapy (CDT) and temperature suggests that the increasing temperature facilitates in its working. The hydroxyl radicals generated by CDT can destroy the structure of bacteria in acidic environments. The germicidal activity of the nanoparticles was determined by the combined action of PTT, CDT, and NO-based gas therapy. The nanoparticles showed bactericidal activity in vitro against bacterial strains Staphylococcus aureus (S. aureus) and Salmonella typhimurium (S. typhimurium). Finally, the anti-infective efficacy in vivo in S. aureus-infected mouse model was demonstrated. Thus, the synergistic antimicrobial effects of NO-generating silica nanoparticles have good potential for the non-antibiotic treatment of bacterial infections in wounds. STATEMENT OF SIGNIFICANCE: Bacterial infections and resistance are challenging health threats. Therefore, the development of an antibiotic-independent method is essential for the treatment of wound bacterial infections. In this study, NO-generating nanoparticles loaded with sodium nitroprusside in copper sulphide-doped mesoporous silica were prepared to control the long-term release of NO using near-infrared laser, which has good efficacy of PTT and CDT. The bactericidal effects of as-prepared nanoparticles against S. aureus and S. typhimurium have been well elucidated. This study proposes a feasible method in the field of NO-based therapy, thus paving the way that will benefit for the treatment of bacterial infections in wounds.

Association between red blood cell distribution width/albumin ratio and all-cause mortality or cardiovascular diseases mortality in patients with diabetic retinopathy: A cohort study.

BACKGROUND: Red blood cell distribution width/albumin ratio (RAR) has been reported as an independent risk factor for diabetic retinopathy (DR), while its association and predictive value in the prognosis of DR patients has not been reported. This study aims to explore the association and predictive value of RAR in the prognosis of DR patients. METHODS: This was a retrospective cohort study based on the National Health and Nutrition Examination Survey (NHANES). The independent variable was RAR, and dependent variables were all-cause mortality and cardiovascular diseases (CVD) mortality. The association between RAR and the risk of all-cause mortality and CVD mortality was assessed using univariate and multivariate cox regression models. The results were shown as HR (hazard ratio) with 95% confidence intervals (CIs). Subgroup analysis based on age or hyperlipidemia was performed. The discrimination of the prediction model was assessed using concordance index (C-index). RESULTS: A total of 725 eligible patients were finally included in this study. The increase of RAR was associated with increased risk of all-cause mortality (HR: 1.15, 95%CI: 1.01-1.31) and CVD mortality (HR: 1.35, 95%CI: 1.12-1.63) after adjusting the covariates. We also found the significant association between higher RAR and higher risk of CVD mortality in DR patients with age < 65 years (HR: 1.35, 95%CI: 1.09-1.67) and with hyperlipidemia (HR: 1.34, 95%CI: 1.10-1.64). C-index of RAR for all-cause mortality and CVD mortality was 0.63 (95%CI: 0.59-0.67) and 0.65 (95%CI: 0.59-0.71), respectively. CONCLUSIONS: Higher RAR was associated with the higher risk of all-cause mortality and CVD mortality in DR patients, and RAR may be a useful predictor for the prognosis of DR patients.

Application of Quantitative Parameters of Computed Tomography Texture Combined with the Detection of Serum Manganese Superoxide Dismutase in the Diagnosis of Adrenocortical Adenoma.

OBJECTIVE: This study aimed to explore the application of quantitative parameters of computed tomography (CT) texture combined with the detection of serum manganese superoxide dismutase (MnSOD) in the diagnosis of adrenocortical adenoma (ACA). METHODS: The study selected 147 patients with suspected ACA received in Yantaishan Hospital from November 2019 to November 2021 as the research objects. These patients were divided into the study group (SG, n = 71, ACA) and the reference group (RG, n = 76, non-ACA) according to the postoperative pathological results to implement CT examination and subsequent serological examination. The quantitative parameters of CT texture and serum MnSOD levels were compared between the two groups, and the receiver operating characteristic curve was used to evaluate the value of single and combined diagnosis of quantitative parameters of CT texture and detection of serum MnSOD. RESULTS: Compared with the RG, the SG had notably lower CT values in the plain scan, venous and delayed phase (p < 0.001) and had overtly higher entropy (p < 0.001). However, no remarkable difference was observed in terms of kurtosis and skewness between the two groups (p > 0.05). The serum MnSOD levels of the SG and RG were 27.26 (24.56, 30.97) U/mL and 43.45 (41.02, 45.08) U/mL, respectively, and the MnSOD level of the SG was significantly lower than that of the RG (p < 0.001). The combined diagnosis of CT entropy parameter and MnSOD detection had higher area under the curve (0.91), sensitivity (88.70%) and specificity (82.90%) than those of each single diagnosis (p < 0.001) and had higher diagnostic efficiency. CONCLUSIONS: The entropy in the quantitative parameters of CT texture and detection of MnSOD can be used for the diagnosis of ACA, and their combined diagnosis effect is good, thus providing a new direction for the clinical identification of the disease.

Stacking Ensemble Learning-Based [18F]FDG PET Radiomics for Outcome Prediction in Diffuse Large B-Cell Lymphoma.

This study aimed to develop an analytic approach based on [18F]FDG PET radiomics using stacking ensemble learning to improve the outcome prediction in diffuse large B-cell lymphoma (DLBCL). Methods: In total, 240 DLBCL patients from 2 medical centers were divided into the training set (n = 141), internal testing set (n = 61), and external testing set (n = 38). Radiomics features were extracted from pretreatment [18F]FDG PET scans at the patient level using 4 semiautomatic segmentation methods (SUV threshold of 2.5, SUV threshold of 4.0 [SUV4.0], 41% of SUVmax, and SUV threshold of mean liver uptake [PERCIST]). All extracted features were harmonized with the ComBat method. The intraclass correlation coefficient was used to evaluate the reliability of radiomics features extracted by different segmentation methods. Features from the most reliable segmentation method were selected by Pearson correlation coefficient analysis and the LASSO (least absolute shrinkage and selection operator) algorithm. A stacking ensemble learning approach was applied to build radiomics-only and combined clinical-radiomics models for prediction of 2-y progression-free survival and overall survival based on 4 machine learning classifiers (support vector machine, random forests, gradient boosting decision tree, and adaptive boosting). Confusion matrix, receiver-operating-characteristic curve analysis, and survival analysis were used to evaluate the model performance. Results: Among 4 semiautomatic segmentation methods, SUV4.0 segmentation yielded the highest interobserver reliability, with 830 (66.7%) selected radiomics features. The combined model constructed by the stacking method achieved the best discrimination performance. For progression-free survival prediction in the external testing set, the areas under the receiver-operating-characteristic curve and accuracy of the stacking-based combined model were 0.771 and 0.789, respectively. For overall survival prediction, the stacking-based combined model achieved an area under the curve of 0.725 and an accuracy of 0.763 in the external testing set. The combined model also demonstrated a more distinct risk stratification than the International Prognostic Index in all sets (log-rank test, all P < 0.05). Conclusion: The combined model that incorporates [18F]FDG PET radiomics and clinical characteristics based on stacking ensemble learning could enable improved risk stratification in DLBCL.

Synthesis of Mesoporous Silica-Supported NiCo Bimetallic Nanocatalysts and Their Enhanced Catalytic Hydrogenation Performance.

In this work, mesoporous silica SBA-16-supported NiCo bimetallic nanocatalysts were synthesized by coimpregnation of Ni and Co precursors followed by calcination and reduction, and various characterization techniques confirm the formation of NiCo bimetallic nanostructures in the catalysts. The synthesized NiCo/SBA-16 shows enhanced catalytic performance for hydrogenation of a series of nitroaromatics. Under the reaction conditions of 80 °C and 1.0 MPa of H2, the yields of aniline for nitrobenzene hydrogenation over NiCo0.3/SBA-16 can reach more than 99% at 2.0 h. The enhanced catalytic performance can be ascribed to the formation of NiCo bimetallic nanostructures, where the synergistic effect between Ni and Co improves their catalytic activities for hydrogenation of nitroaromatics.

Enhanced Alkene Selectivity for Transfer Semihydrogenation of Alkynes over Electron-Deficient Pt Nanoparticles Encapsulated in Hollow Silica Nanospheres.

In this work, we report that Pt nanoparticles confined in hollow porous silica nanospheres (Pt@HPSNs) function as highly selective catalysts for the transfer hydrogenation of phenylacetylene to styrene with ammonia borane. Relative to the deep hydrogenation of phenylacetylene to ethylbenzene over the supported Pt/SiO2, Pt@HPSNs exhibit above 88% of styrene selectivity at nearly 100% of phenylacetylene conversions, and the high selectivity of Pt@HPSNs can be maintained even at high ammonia borane/phenylacetylene ratios and longer reaction time. The Pt 4f X-ray photoelectron spectrum of Pt@HPSNs shows a remarkable ∼1.5 eV shift to high binding energy, proving the nature of electron deficiency of such encapsulated Pt nanoparticles. Combined with extremely minor transfer hydrogenation of styrene to ethylbenzene when styrene as substrates, the enhanced styrene selectivity of Pt@HPSNs is ascribed to the electron deficiency of encapsulated Pt nanoparticles, which leads to the fast desorption of styrene and thus avoids deep hydrogenation.

A novel analytical approach for outcome prediction in newly diagnosed NSCLC based on [18F]FDG PET/CT metabolic parameters, inflammatory markers, and clinical variables.

OBJECTIVES: To develop a novel analytical approach based on 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) metabolic parameters, serum inflammatory markers, and clinical variables to improve the outcome prediction in NSCLC. METHODS: A total of 190 newly diagnosed NSCLC patients who underwent pretreatment [18F]FDG PET/CT were retrospectively enrolled and divided into a training cohort (n = 127) and a test cohort (n = 63). Cox regression analysis was used to investigate the predictive values of PET metabolic parameters, inflammation markers, and clinical variables for progression-free survival (PFS) and overall survival (OS). Based on the results of multivariate analysis, PET-based, clinical, and combined models were constructed. The predictive performance of different models was evaluated using time-dependent ROC curve analysis, Harrell concordance index (C-index), calibration curve, and decision curve analysis. RESULTS: The combined models incorporating SULmax, MTV, NLR, and ECOG PS demonstrated significant prognostic superiority over PET-based models, clinical models, and TNM stage in terms of both PFS (C-index: 0.813 vs. 0.786 vs. 0.776 vs. 0.678, respectively) and OS (C-index: 0.856 vs. 0.792 vs. 0.781 vs. 0.674, respectively) in the training cohort. Similar results were observed in the test cohort for PFS (C-index: 0.808 vs. 0.764 vs. 0.748 vs. 0.679, respectively) and OS (C-index: 0.836 vs. 0.785 vs. 0.726 vs. 0.660, respectively) prediction. The combined model calibrated well in two cohorts. Decision curve analysis supported the clinical utility of the combined model. CONCLUSIONS: We reported a novel analytical approach combining PET metabolic information with inflammatory biomarker and clinical characteristics, which could significantly improve outcome prediction in newly diagnosed NSCLC. KEY POINTS: • The nomogram incorporating SULmax, MTV, NLR, and ECOG PS outperformed the TNM stage for outcome prediction in patients with newly diagnosed NSCLC. • The established nomogram could provide refined prognostic stratification.

Pt nanoparticles confined in hollow silica nanoreactors as highly efficient catalysts for semihydrogenations of alkynes at atmospheric H2 pressure.

In this work, Pt nanoparticles encapsulated hollow porous silica nanoreactors (Pt@HPSNs) was synthesized in one-pot by a reverse microemulsion system, and they exhibit good catalytic efficiency and stability for semihydrogenations of alkynes. The key design concept is to form Pt hydroxide nanoparticles mixed poly(ethyleneimine) nano-aggregates in water droplets, which further functions as seeds for silica deposition and the void templates to form the central voids. The Pt@HPSNs illustrate a wide adaptability for semihydrogenations of a series of terminal alkynes to the corresponding alkenes at mild reaction conditions, and demonstrate high yields of styrene for semihydrogenation of phenylacetylene, showing good catalytic efficiency for hydrogenation of phenylacetylene to styrene at atmospheric H2 pressure. The enhanced catalytic performance of Pt@HPSNs are ascribed to their hollow porous nanostructures, where the confinement of Pt nanoparticles in voids increase the structural stability and the confinement effect may increase the collision of reactants and Pt, resulting in improved catalytic efficiency.

GSH-depleting and H2O2-self-supplying hybrid nanozymes for intensive catalytic antibacterial therapy by photothermal-augmented co-catalysis.

Nanozyme-based chemodynamic therapy (CDT) has shown tremendous potential in the treatment of bacterial infections. However, the CDT antibacterial efficacy is severely limited by the catalytic activity of nanozymes or the infection microenvironments such as insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH). Herein, a versatile hybrid nanozyme (MoS2/CuO2) is rationally constructed by simply decorating ultrasmall CuO2 nanodots onto lamellar MoS2 platelets of hydrangea-like MoS2 nanocarrier via a covalent Cu-S bond. The MoS2/CuO2 nanozyme exhibits the peroxidase-mimic activity for catalytically converting H2O2 produced by acid-triggered decomposition of the decorated CuO2 into hydroxyl radical (•OH). Meanwhile, the MoS2/CuO2 can consume GSH overexpressed in the infection sites via redox reaction mediated by polyvalent transition metal ions (Cu2+ and Mo6+) for enhanced CDT. More importantly, MoS2 support can promote the conversion of Cu2+ to Cu+ by a co-catalytic reaction based on the Mo4+/Mo6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS2/CuO2 nanozymes possesses a desirable catalytic property, as well as a remarkably improved antibacterial efficiency both in vitro and in vivo. Taken together, this study proposes a synergetic multiple enhancement strategy to successfully construct the versatile hybrid nanozymes for intensive in vivo PTT/CDT dual-mode anti-infective therapy. STATEMENT OF SIGNIFICANCE: Chemodynamic therapy (CDT) has shown great potentialities in the treatment of bacterial infections, while its therapeutic efficiency is severely limited by the infection microenvironments such as insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH). Here, we rationally construct a hybrid nanozyme (MoS2/CuO2) with peroxidase-like activity that can enhance CDT by regulating local microenvironments, that is, simultaneously self-supplying H2O2 and consuming GSH. Importantly, MoS2 support can promote the conversion of Cu2+ to Cu+ by the Mo4+/Mo6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS2/CuO2 shows desirable PTT/CDT dual-mode antibacterial efficacy both in vitro and in vivo. This study proposes a versatile hybrid nanozyme with multiple enhancement effects for intensive in vivo anti-infective therapy.

Effects of Stocking Density on Fatty Acid Metabolism by Skeletal Muscle in Mice.

Specific pathogen-free (SPF) grade laboratory animals are kept in specific cages for life. The limited space could affect the characterization of colonization and dynamic changes related to gut microorganisms, and affect adipokines, even further affecting the fat synthesis and muscle quality of animals. The objective of this study was to analyze the stocking density on the dynamic distribution of gut microbiota, fat synthesis and muscle quality of SPF grade Kunming mice. Three housing densities were accomplished by raising different mice per cage with the same floor size. Kunming mice were reared at low stocking density (LSD, three mice a group), medium stocking density (MSD, 5 mice a group), and high stocking density (HSD, 10 mice a group) for 12 weeks. The results demonstrated that the stocking density affected intestinal microbial flora composition. We found that compared with the MSD group, the abundance of Lactobacillus in the LSD group and the HSD group decreased, but the abundance of unclassified_Porphyromonadaceae increased. Moreover, fat synthesis and muscle quality were linked to the intestinal microbial flora and stocking density. Compared with the LSD group and the HSD group, the MSD group had a more balanced gut flora, higher fat synthesis and higher muscle quality. Overall, this study demonstrated that stocking density could affect gut microbiota composition, and reasonable stocking density could improve fat synthesis and muscle quality. Our study will provide theoretical support for the suitable stocking density of laboratory animals.

Synthesis of Pd-CoxOy Hybrid Nanostructure-Encapsulated Hollow Silica Nanospheres through Reverse Microemulsion Systems and Their Application as Efficient Hydrodechlorination Catalysts.

Pd-CoxOy heteroaggregate-encapsulated hollow porous silica nanoreactors (Pd-CoxOy@HPSNs) were synthesized by a reverse microemulsion system. The key design of the developed reverse microemulsion system is to use poly(ethyleneimine) in the water droplets as the void templates for silica deposition and for anchoring the catalytic functionality inside the hollow silica nanospheres. The synthesized Pd-CoxOy@HPSNs contain ∼3 nm Pd-CoxOy hybrid nanostructures in ∼10 nm central cavities of silica nanospheres and illustrated a significantly promoted efficiency for hydrodechlorination of a series of chlorophenols into phenols under mild reaction conditions. The catalytic enhancement of Pd-CoxOy@HPSNs is ascribed to the synergistic effect between Pd and CoxOy and the protection of silica shells to the inner catalytic functionality.

Highly effective and chemoselective hydrodeoxygenation of aromatic alcohols.

Effective hydrodeoxygenation (HDO) of aromatic alcohols is very attractive in both conventional organic synthesis and upgrading of biomass-derived molecules, but the selectivity of this reaction is usually low because of the competitive hydrogenation of the unsaturated aromatic ring and the hydroxyl group. The high activity of noble metal-based catalysts often leads to undesired side reactions (e.g., saturation of the aromatic ring) and excessive hydrogen consumption. Non-noble metal-based catalysts suffer from unsatisfied activity and selectivity and often require harsh reaction conditions. Herein, for the first time, we report chemoselective HDO of various aromatic alcohols with excellent selectivity, using porous carbon-nitrogen hybrid material-supported Co catalysts. The C-OH bonds were selectively cleaved while leaving the aromatic moiety intact, and in most cases the yields of targeted compounds reached above 99% and the catalyst could be readily recycled. Nitrogen doping on the carbon skeleton of the catalyst support (C-N matrix) significantly improved the yield of the targeted product. The presence of large pores and a high surface area also improved the catalyst efficiency. This work opens the way for efficient and selective HDO reactions of aromatic alcohols using non-noble metal catalysts.

Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke.

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.

A novel miRNA-762/NFIX pathway modulates LPS-induced acute lung injury.

Severe acute lung injury (ALI) cause significant morbidity and mortality worldwide. MicroRNAs (miRNAs) are possible biomarkers and therapeutic targets for ALI. We aimed to explore the role of miR-762, a known oncogenic factor, in the pathogenesis of ALI. Levels of miR-762 in lung tissues of LPS-treated ALI mice and blood cells of patients with lung injury were measured. Injury of human lung epithelial cell line A549 was induced by LPS stimulation. A downstream target of miR-762, NFIX, was predicted using online tools. Their interactions were validated by luciferase reporter assay. Effects of targeted regulation of the miR-762/NFIX axis on cell proliferation, apoptosis, and inflammatory responses were tested in vitro in A549 cells in vivo with an ALI mouse model. We found that upregulation of miR-762 expression and downregulation of NFIX expression were associated with lung injury. Either miR-762 inhibition or NFIX overexpression in A549 lung cells significantly attenuated LPS-mediated impairment of cell proliferation and viability. Notably, increasing expressions of miR-762 inhibitor or NFIX in vivo via airway lentivirus infection alleviated the LPS-induced ALI in mice. Further, targeted downregulation of miR-762 expression or upregulation of NFIX expression in A549 cells markedly down-regulates NF-κB/IRF3 activation, and substantially reduces the production of inflammatory factors, including TNF-α, IL-6, and IL-8. This study reveals a novel role for the miR-762/NFIX pathway in ALI pathogenesis and sheds new light on targeting this pathway for diagnosis, prevention, and therapy.

Influencing Factors and Prognostic Value of 18F-FDG PET/CT Metabolic and Volumetric Parameters in Non-Small Cell Lung Cancer.

OBJECTIVE: This study aims to explore factors influencing metabolic and volumetric parameters of [18F]fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging in non-small cell lung cancer (NSCLC) and the predictive value for prognosis of NSCLC. METHODS: Retrospective analysis was performed on 133 NSCLC patients who received 18F-FDG PET/CT imaging. After 18F-FDG injection at 3.7 MBq/kg, 1 h early imaging and 2 h delayed imaging were performed. The metabolic and volumetric parameters such as SUVmax, SUVpeak, SULmax, SULpeak, MTV and TLG were measured. The tumor markers including CFYRA21-1, NSE, SCC-ag and the immunohistochemical biomarkers including Ki-67, P53 and CK-7 were examined. All patients were followed up for 24 months, and the 1-year and 2-year overall survival rate (OS) were recorded. RESULTS: There were significant differences in metabolic and volumetric parameters (SUVmax, SUVpeak, SULmax, SULpeak and TLG) between adenocarcinoma and squamous cell carcinoma of NSCLC. SUVmax, SUVpeak, SULmax, SULpeak, MTV and TLG were correlated with tumor marker NSE and TNM stage. MTV and TLG were related to CYFRA21-1, and only MTV was associated with SCC-ag. SUVpeak and SULmax were related to P53. In addition, early SULpeak and delayed MTV were significant prognostic factors of 1-year OS, while early SUVpeak, delayed TLG and delayed MTV were predictive factors of 2-year OS in NSCLC. CONCLUSION: The metabolic and volumetric parameters of 18F-FDG PET/CT were related to a variety of factors such as NSE, CFYRA21-1, SCC-ag, P53 and TNM stage, and have a predictive value in prognosis of NSCLC.

Distinct roles of PI3Kδ and PI3Kγ in a toluene diisocyanate-induced murine asthma model.

TDI-induced asthma is characterized by neutrophil-dominated airway inflammation and often associated with poor responsiveness to steroid treatment. Both PI3Kδ and PI3Kγ have been demonstrated to play important proinflammatory roles in ovalbumin-induced asthma. We've already reported that blocking pan PI3K effectively attenuated TDI-induced allergic airway inflammation. Yet the specific functions of PI3Kδ and PI3Kγ in TDI-induced asthma are still unclear. Male BALB/c mice were first dermally sensitized and then challenged with TDI to generate an asthma model. Sellective inhibitors of PI3Kδ (IC-87114, AMG319) and PI3Kγ (AS252424, AS605240) were respectively given to the mice after each airway challenge. Treatment with IC-87114 or AMG319 after TDI exposure led to significantly decreased airway hyperresponsiveness (AHR), less neutrophil and eosinophil accumulation, attenuated airway smooth muscle (ASM) thickening, less M1 and M2 macrophages in lung, as well as lower levels of IL-4, IL-5, IL-6 and IL-18 in bronchoalveolar lavage fluid (BALF) and recovered IL-10 production. While mice treated with AS252424 or AS605240 had increased AHR, more severe ASM thickening, larger numbers of neutrophils and eosinophils, more M1 but less M2 macrophages, and higher BALF levels of IL-4, IL-5, IL-6, IL-10, IL-12, IL-18 when compared with those treated with vehicle. These data revealed that pharmacological inhibition of PI3Kδ attenuates TDI-induced airway inflammation while PI3Kγ inhibition exacerbates TDI-induced asthma, indicating distinct biological functions of PI3Kδ and PI3Kγ in TDI-induced asthma.

Protective effects of N-acetylcysteine on a chemical-induced murine model of asthma.

INTRODUCTION: Oxidative stress is involved in the pathophysiology of inflammatory airway diseases, including asthma. In this study, we elucidated the possible protective effects of the antioxidant N-acetylcysteine (NAC) on a toluene diisocyanate (TDI)-induced murine asthma model. METHODS: Male BALB/c mice were sensitized and challenged with TDI to generate a chemical-induced asthma model. NAC was given intraperitoneally to mice immediately after each TDI challenge. Airway reactivity to methacholine and bronchoalveolar lavage fluid was analyzed. Lungs were examined by histology. RESULTS: NAC treatment dramatically reduced the increased airway hyperresponsiveness, inflammatory infiltration, and goblet cell metaplasia in TDI-exposed mice. Numbers of total cells, neutrophils, and eosinophils in the bronchoalveolar lavage fluid of TDI-challenged mice were significantly higher than vehicle control, but the administration of NAC decreased these inflammatory cell counts. TDI exposure led to significantly increased levels of interleukin 4 (IL-4) and IL-5, which were also suppressed by NAC. In addition, diminished lung reduced oxidized glutathione ratio and superoxide dismutase activity were observed after TDI challenge, and these changes were attenuated by NAC. CONCLUSION: NAC treatment has beneficial effects in TDI-induced asthma.