Clinical characteristics of obese, fixed airway obstruction, exacerbation-prone phenotype and comorbidities among severe asthma patients: a single-center study.

BACKGROUND: Severe asthma places a large burden on patients and society. The characteristics of patients with severe asthma in the Chinese population remain unclear. METHODS: A retrospective review was conducted in patients with severe asthma. Demographic and clinical data were collected. Patients were grouped according to phenotypes in terms of exacerbations, body mass index (BMI) and fixed airway obstruction (FAO) status, and the characteristics of different groups were compared. Comorbidities, factors that influence asthma phenotypes, were also analyzed in the study. RESULTS: A total of 228 patients with severe asthma were included in our study. They were more likely to be overweight or obese. A total of 41.7% of the patients received GINA step 5 therapy, and 43.4% had a history of receiving regular or intermittent oral corticosteroids (OCS). Severe asthmatic patients with comorbidities were prone to have more asthma symptoms and decreased quality of life than patients without comorbidities. Patients with exacerbations were characterized by longer duration of asthma, poorer lung function, and worse asthma control. Overweight or obese patients tended to have more asthma symptoms, poorer lung function and more asthma-related comorbidities. Compared to patients without FAO, those in the FAO group were older, with longer duration of asthma and more exacerbations. CONCLUSION: The existence of comorbidities in patients with severe asthma could result in more asthma symptoms and decreased quality of life. Patients with exacerbations or with overweight or obese phenotypes were characterized by poorer lung function and worse asthma control. Patients with FAO phenotype tended to have more exacerbations.

Electric manipulation on deformation of ionic ferrofluid sessile droplets.

Active electric-driven droplet manipulation in digital microfluidics constitutes a promising domain owing to the unique and programmable wettability inherent in sessile ionic droplets. The coupling between the electric field and flow field enables precise control over wetting characteristics and droplet morphology. This study delves into the deformation phenomena of ionic sessile ferrofluid droplets in ambient air induced by uniform electric fields. Under the assumption of a pinned mode throughout the process, the deformation is characterized by variations in droplet height and contact angle in response to the applied electric field intensity. A numerical model is formulated to simulate the deformation dynamics of ferrofluid droplets, employing the phase field method for tracking droplet deformation. The fidelity of the numerical outcomes is assessed through the validation process, involving a comparison of droplet geometric deformations with corresponding experimental results. The impact of the electric field on the deformation of dielectric droplets is modulated by parameters such as electric field strength and droplet size. Through meticulously designed experiments, the substantial influence of both field strength and droplet size is empirically verified, elucidating the behavior of ionic sessile droplets. Considering the interplay of electric force, viscous force, and interfacial tension, the heightened field intensity is observed to effectively reduce the contact angle, augment droplet height, and intensify internal droplet flow. Under varying electric field conditions, droplets assume diverse shapes, presenting a versatile approach for microfluidic operations. The outcomes of this research hold significant guiding implications for microfluidic manipulation, droplet handling, and sensing applications.

Edaravone alleviated allergic airway inflammation by inhibiting oxidative stress and endoplasmic reticulum stress.

Oxidative stress and endoplasmic reticulum stress (ERS) was associated with the development of asthma. Edaravone (EDA) plays a classical role to prevent the occurrence and development of oxidative stress-related diseases. Herein, we investigated the involvement and signaling pathway of EDA in asthma, with particular emphasis on its impact on type 2 innate lymphoid cells (ILC2) and CD4+T cells, and then further elucidated whether EDA could inhibit house dust mite (HDM)-induced allergic asthma by affecting oxidative stress and ERS. Mice received intraperitoneally injection of EDA (10 mg/kg, 30 mg/kg), dexamethasone (DEX) and N-acetylcysteine (NAC), with the latter two used as positive control drugs. DEX and high dose of EDA showed better therapeutic effects in alleviating airway inflammation and mucus secretion in mice, along with decreasing eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF) than NAC. Further, the protein levels of IL-33 in lung tissues were inhibited by EDA, leading to reduced activation of ILC2s in the lung. EDA treatment alleviated the activation of CD4+ T cells in lung tissues of HDM-induced asthmatic mice and reduced Th2 cytokine secretion in BALF. ERS-related markers (p-eIF2α, IRE1α, CHOP, GRP78) were decreased after treatment of EDA compared to HDM group. Malondialdehyde (MDA), glutathione (GSH), hydrogen peroxide (H2O2), and superoxide dismutase (SOD) were detected to evaluate the oxidant stress in lung tissues. EDA showed a protective effect against oxidant stress. In conclusion, our findings demonstrated that EDA could suppress allergic airway inflammation by inhibiting oxidative stress and ERS, suggesting to serve as an adjunct medication for asthma in the future.

The role of moesin in diagnosing and assessing severity of lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare disease which is easily misdiagnosed. Vascular endothelial growth factor D (VEGF-D), as the most common biomarker, however, is not so perfect for the diagnosis and severity assessment of LAM. MATERIALS AND METHODS: The isobaric tags for relative and absolute quantitation (iTRAQ)-based method was used to identify a cytoskeleton protein, moesin. 84 patients with LAM, 44 patients with other cystic lung diseases (OCLDs), and 37 healthy control subjects were recruited for collecting blood samples and clinical data. The levels of moesin in serum were evaluated by ELISA. The relationships of moesin with lymphatic involvement, lung function, and treatment decision were explored in patients with LAM. RESULTS: The candidate protein moesin was identified by the proteomics-based bioinformatic analysis. The serum levels of moesin were higher in patients with LAM [219.0 (118.7-260.5) pg/mL] than in patients with OCLDs (125.8 ± 59.9 pg/mL, P < 0.0001) and healthy women [49.6 (35.5-78.9) ng/mL, P < 0.0001]. Moesin had an area under the receiver operator characteristic curve (AUC) of 0.929 for predicting LAM diagnosis compared to healthy women (sensitivity 81.0%, specificity 94.6%). The combination of moesin and VEGF-D made a better prediction in differentiating LAM from OCLDs than moesin or VEGF-D alone. Moreover, elevated levels of moesin were related to lymphatic involvement in patients with LAM. Moesin was found negatively correlated with FEV1%pred, FEV1/FVC, and DLCO%pred (P = 0.0181, r = - 0.3398; P = 0.0067, r = - 0.3863; P = 0.0010, r = - 0.4744). A composite score combining moesin and VEGF-D improved prediction for sirolimus treatment, compared with each biomarker alone. CONCLUSION: Higher levels of moesin in serum may indicate impaired lung function and lymphatic involvement in patients with LAM, suggest a more serious condition, and provide clinical guidance for sirolimus treatment.

FGF10 attenuates allergic airway inflammation in asthma by inhibiting PI3K/AKT/NF-κB pathway.

BACKGROUND: The effect of fibroblast growth factor 10 (Fgf10) against allergic asthma has remained unclear, despite its importance in lung development and homeostasis maintenance. The purpose of this study was to investigate the protective effect and potential mechanism of Fgf10 on asthma. METHOD: House Dust Mite (HDM)-induced asthma mice were administered recombinant Fgf10 intranasally during activation. Flow cytometry and ELISA were performed to determine type of inflammatory cells and type 2 cytokines levels in bronchoalveolar lavage fluid (BALF). Hematoxylin and eosin (H&E) and periodic acid - Schiff (PAS) staining of lung sections were conducted to evaluate histopathological assessment. Transcriptome profiling was analyzed using RNA-seq, followed by bioinformatics and network analyses to investigate the potential mechanisms of Fgf10 in asthma. RT-qPCR was also used to search for and validate differentially expressed genes in human Peripheral Blood Mononuclear Cells (PBMCs). RESULTS: Exogenous administration of Fgf10 alleviated HDM-induced inflammation and mucus secretion in lung tissues of mice. Fgf10 also significantly inhibited the accumulation of eosinophils and type 2 cytokines (IL-4, IL-5, and IL-13) in BALF. The PI3K/AKT/NF-κB pathway may mediate the suppressive impact of Fgf10 on the asthma inflammation. Through RNA-seq analysis, the intersection of 71 differentially expressed genes (DEGs) was found between HDM challenge and Fgf10 treatment. GO and KEGG enrichment analyses indicated a strong correlation between the DEGs and different immune response. Immune infiltration analysis predicted the differential infiltration of five types of immune cells, such as NK cells, dendritic cells, monocytes and M1 macrophages. PPI analysis determined hub genes such as Irf7, Rsad2, Isg15 and Rtp4. Interestingly, above genes were consistently altered in human PBMCs in asthmatic patients. CONCLUSION: Asthma airway inflammation could be attenuated by Fgf10 in this study, suggesting that it could be a potential therapeutic target.

Magnetic regulation on evaporation behavior of ferrofluid sessile droplets.

Active magnetic regulation is an emerging subject due to the special and programmable wettability of the sessile ferrofluid droplet. The interaction between liquid and externally applied magnetic field gives rise to controllable spreading and thus evaporation. This work reports the experimental and numerical results of the natural evaporation of a ferrofluid droplet under the effect of a nonuniform magnetic field. The evaporation process of droplets is described into two stages in terms of the geometric distortion and the appearance of the deposition pattern. The presence of the magnetic field leads to a transition of droplet drying from the disk shape with a ring to multiple peaks. A numerical model is established to simulate the evaporation process of ferrofluid droplets with the arbitrary Lagrangian-Eulerian method for tracking droplet deformation. The increasing magnetic flux could effectively enlarge the contact radius and enhance the internal flow of the ferrofluid droplet, thus promoting the evaporation process. The numerical results are verified by comparing the droplet geometry deformation with the experimental results. In both the numerical and experimental investigations, the externally applied magnetic field shortens the process of ferrofluid droplet evaporation. The design and optimization of the magnetic field play an important role in regulating ferrofluid droplet evaporation, which in turn facilitates technological advances in industries such as evaporative cooling and inkjet printing.

A crowd clustering prediction and captioning technique for public health emergencies.

The COVID-19 pandemic has come to the end. People have started to consider how quickly different industries can respond to disasters due to this public health emergency. The most noticeable aspect of the epidemic regarding news text generation and social issues is detecting and identifying abnormal crowd gatherings. We suggest a crowd clustering prediction and captioning technique based on a global neural network to detect and caption these scenes rapidly and effectively. We superimpose two long convolution lines for the residual structure, which may produce a broad sensing region and apply our model's fewer parameters to ensure a wide sensing region, less computation, and increased efficiency of our method. After that, we can travel to the areas where people are congregating. So, to produce news material about the present occurrence, we suggest a double-LSTM model. We train and test our upgraded crowds-gathering model using the ShanghaiTech dataset and assess our captioning model on the MSCOCO dataset. The results of the experiment demonstrate that using our strategy can significantly increase the accuracy of the crowd clustering model, as well as minimize MAE and MSE. Our model can produce competitive results for scene captioning compared to previous approaches.

Outstanding Performance of the Deep Eutectic Solvent-Based Aqueous Biphasic System Constructed with Sodium Citrate for a Green Gold Separation.

Aqueous biphasic systems (ABSs) that are based on deep eutectic solvents (DESs) are environmentally benign systems to use for metal ion separation. In this work, a series of DESs was synthesized for the first time with PEG 400 as hydrogen bond donors and tetrabutylphonium bromide (P4Br), tetrabutylammonium bromide (N4Br), or tetrabutylammonium chloride (N4Cl) as hydrogen bond acceptors, and then they were combined with citrate (Na3C6H5O7), which is eco-friendly, to construct an ABS for use in the separation of Au(I) from an aurocyanide solution. Phase diagrams of DESs + Na3C6H5O7 + H2O systems were constructed using the experimentally measured data. Multiple factors that affect the efficiency of the gold extraction were studied; these factors were the species of salt or DES and their content, the equilibrium pH, the oscillation time, and the initial gold concentration. Gold(I) is preferentially retained in the DES-rich phase, and the P4Br:PEG 1:2 + Na3C6H5O7 + H2O system has a high extraction efficiency of 100.0% under optimized conditions. FT-IR, NMR, and TEM characterizations and DFT calculations show that the migration of Au(I) from the salt-rich to the DES-rich phase follows an ion exchange mechanism. Specifically, Au(CN)2- replaces Br- in the original P4Br and generates a stable ion pair with the quaternary phosphonium salt cation, P+, and this replacement is driven by electrostatic attractions. A new strong hydrogen bond network simultaneously forms between the anionic Au(CN)2- and the -OH group in the PEG 400 component. Finally, the gold of Au(I)-loaded P4Br:PEG 1:2 can be successfully reduced by sodium borohydride with an efficiency of 100.0%. The strategy to extract gold(I) from alkaline cyanide solutions using an ABS based on DESs as proposed in this work provides a potential platform for developing green technology for recovering gold.

Perturbation of arachidonic acid and glycerolipid metabolism promoted particulate matter-induced inflammatory responses in human bronchial epithelial cells.

Particulate matter (PM) has become the main risk factor for public health, being linked with an increased risk of respiratory diseases. However, the potential mechanisms underlying PM-induced lung injury have not been well elucidated. In this study, we systematically integrated the metabolomics, lipidomics, and transcriptomics data obtained from the human bronchial epithelial cells (HBECs) exposed to PM to reveal metabolic disorders in PM-induced lung injury. We identified 170 differentially expressed metabolites (82 upregulated and 88 downregulated metabolites), 218 differentially expressed lipid metabolites (125 upregulated and 93 downregulated lipid metabolites), and 1417 differentially expressed genes (643 upregulated and 774 downregulated genes). Seven key metabolites (prostaglandin E2, inosinic acid, L-arginine, L-citrulline, L-leucine, adenosine, and adenosine monophosphate), and two main lipid subclasses (triglyceride and phosphatidylcholine) were identified in PM-exposed HBECs. The amino acid metabolism, lipid metabolism, and carbohydrate metabolism were the significantly enriched pathways of identified differentially expressed genes. Then, conjoint analysis of these three omics data and further qRT-PCR validation showed that arachidonic acid metabolism, glycerolipid metabolism, and glutathione metabolism were the key metabolic pathways in PM-exposed HBECs. The knockout of AKR1C3 in arachidonic acid metabolism or GPAT3 in glycerolipid metabolism could significantly inhibit PM-induced inflammatory responses in HBECs. These results revealed the potential metabolic pathways in PM-exposed HBECs and provided a new target to protect from PM-induced airway damage.

Comprehensive analysis of transcriptome-wide m6A methylome in the lung tissues of mice with acute particulate matter exposure.

Particulate matter (PM) exposure is identified as a critical risk factor for chronic airway diseases, but the biological mechanism of PM-induced lung damage was not fully elucidated. The m6A methylation, as the main member of epigenetic modifications, has been found to play an important role in different pulmonary diseases, but its regulatory effect on PM-induced lung damage remains unknown. This study firstly used the methylated RNA immunoprecipitation sequencing (MeRIP-seq) to reveal the m6A methylome profiles in the lung tissues of mice with acute PM exposure. Compared with the normal control, a total of 2210 differentially hypermethylated m6A peaks within 1879 genes and 1278 differentially hypomethylated m6A peaks within 1153 genes were identified in the PM-exposed group. Conjoint analysis of MeRIP-seq and high-throughput sequencing for RNA (RNA-seq) data predicated several potential pathways including MAPK signaling pathway, cell senescence, and cell cycle. Four m6A-modified differentially expressed genes (IL-1a, IL-1b, ADAM-8, and HMOX-1) were selected for validation using MeRIP-qPCR. Furthermore, the m6A-modified IL-1a promoted PM-induced inflammation via regulating MAPK signaling pathway. These results provide a new insight into the biological mechanism of PM-induced lung damage, and help us to develop new methods to prevent and treat PM-induced adverse health effects.

Edaravone Attenuated Particulate Matter-Induced Lung Inflammation by Inhibiting ROS-NF-κB Signaling Pathway.

Background: Particulate matter (PM) exposure is related to mitochondria dysfunction and airway inflammation. Antioxidant drug edaravone (EDA) is reported to improve the occurrence and development of oxidative stress-related diseases. At present, there is no data on whether EDA can alleviate lung inflammation caused by PM. Methods: The anti-inflammatory effects of EDA were investigated in urban PM-induced human bronchial epithelial cells (HBECs) and C57/BL6J mouse models. In vitro, its effects on the production of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and inflammatory cytokines were assessed by DCFH-DA staining, JC-1 assay, and real-time PCR, respectively. In vivo, the oxidant stress in lung tissues was assessed by dihydroethidium (DHE) staining and malondialdehyde (MDA) activity, and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were assessed by ELISA, respectively. Furthermore, the potential signaling pathways were studied by siRNA transfection and western blot. Results: PM increased the expression of inflammatory cytokines and protein, including IL-6, IL-1α, IL-1ß, and COX-2, while these alternations were significantly alleviated following EDA treatment in a dose-dependent manner. EDA treatment also alleviated the inflammatory responses in lung tissues of PM-exposed mice. We further showed mitochondrial dysfunction in PM-exposed HBECs and mice, which were reversed by EDA treatment. Moreover, the phosphorylation of NF-κB p65 in PM-exposed HBECs and mice was weakened by EDA. Transfection with NF-κB p65 siRNA further inhibited PM-induced inflammation in HBECs. Conclusion: We demonstrated that EDA treatment had a protective role in PM-induced lung inflammation through maintaining mitochondrial balance and regulating the ROS-NF-κB p65 signaling pathway. This provided a new therapeutic method for PM-induced lung inflammation in the future.

ROS-Responsive miR-150-5p Downregulation Contributes to Cigarette Smoke-Induced COPD via Targeting IRE1α.

MicroRNAs (miRNAs) have been reported in human diseases, in which chronic obstructive pulmonary disease (COPD) is included. Herein, we assessed the role along with the possible mechanisms of miR-150-5p in cigarette smoke- (CS-) induced COPD. The plasma miR-150-5p expression was lower in patients with COPD and acute exacerbation of COPD (AECOPD) and was related to disease diagnosis, disease severity, and lung function. Consistently, exposure to CS for 3 months or 3 days reduced miR-150-5p in the plasma and lung tissues of mice, and CS extract (CSE) inhibited miR-150-5p in human bronchial epithelial cells (HBECs) in a concentration along with time-dependent approach. In vitro, miR-150-5p overexpression decreased the contents of inflammatory factors interleukin- (IL-) 6, IL-8 along with cyclooxygenase-2 (COX-2), and endoplasmic reticulum (ER) stress markers glucose-regulated protein (GRP) 78 and C/-EBP homologous protein (CHOP) and promoted cell migrate. Mechanistically, miR-150-5p could bind with the 3'-untranslated region (UTR) of inositol requiring enzyme 1α (IRE1α), while IRE1α overexpression obliterated the impacts of miR-150-5p. Besides, N-acetyl-cysteine (NAC) reversed CSE-induced miR-150-5p downregulation and its downstream effects. In vivo, miR-150-5p overexpression counteracted CS-triggered IRE1α upregulation, inflammation, and ER stress in the lung tissues of mice. In conclusion, our findings illustrated that ROS-mediated downregulation of miR-150-5p led to CS-induced COPD by inhibiting IRE1α expression, suggesting to serve as a useful biomarker for diagnosing and treating COPD.

Droplet Manipulation under a Magnetic Field: A Review.

The magnetic manipulation of droplets is one of the emerging magnetofluidic technologies that integrate multiple disciplines, such as electromagnetics, fluid mechanics and so on. The directly driven droplets are mainly composed of ferrofluid or liquid metal. This kind of magnetically induced droplet manipulation provides a remote, wireless and programmable approach beneficial for research and engineering applications, such as drug synthesis, biochemistry, sample preparation in life sciences, biomedicine, tissue engineering, etc. Based on the significant growth in the study of magneto droplet handling achieved over the past decades, further and more profound explorations in this field gained impetus, raising concentrations on the construction of a comprehensive working mechanism and the commercialization of this technology. Current challenges faced are not limited to the design and fabrication of the magnetic field, the material, the acquisition of precise and stable droplet performance, other constraints in processing speed and so on. The rotational devices or systems could give rise to additional issues on bulky appearance, high cost, low reliability, etc. Various magnetically introduced droplet behaviors, such as deformation, displacement, rotation, levitation, splitting and fusion, are mainly introduced in this work, involving the basic theory, functions and working principles.

Clinical Characteristics and Prognosis of Allergic Bronchopulmonary Aspergillosis: A Retrospective Cohort Study.

BACKGROUND: The clinical features, treatment, and prognosis of allergic bronchopulmonary aspergillosis (ABPA) are not well-defined. OBJECTIVE: We aimed to investigate the clinical characteristics, therapy, and prognosis of ABPA to aid its clinical recognition. METHODS: A total of 232 patients with ABPA were analyzed retrospectively. The characteristics of ABPA in terms of its misdiagnosis, computed tomography classification, therapy, and its relationship with asthma were analyzed, and risk factors for acute exacerbation of ABPA were analyzed based on follow-up data. RESULTS: Of the 232 ABPA patients, 132 had a history of misdiagnosis. Compared with the misdiagnosed patients, ABPA patients with central bronchiectasis, a high total eosinophil count, and mucus plugs were less likely to be misdiagnosed. Compared with serological ABPA, ABPA with central bronchiectasis was more likely to occur in older people and in patients with mucus plugs, and decreased forced vital capacity and diffusing capacity for carbon monoxide. ABPA patients with asthma were more likely to have bronchiectasis, decreased lung function in 1 s FEV1 and FEV1/FVC, and shorter time to first acute exacerbation compared with ABPA patients without asthma. Patients receiving glucocorticoids plus antifungal therapy had a longer time to first exacerbation than those receiving glucocorticoid therapy alone. Univariate and multivariate analyses revealed that duration of asthma history, duration of misdiagnosis, mucus plugs, and poor pulmonary function were risk factors for acute exacerbation of ABPA. CONCLUSION: To our knowledge, this is the largest sample size study of ABPA in China. ABPA patients with a history of asthma and/or central bronchiectasis on high-resolution computed tomography are prone to frequent acute exacerbations. The use of glucocorticoids combined with antifungal drugs can prolong the time to the first acute exacerbation in ABPA patients. Longer durations of asthma history and misdiagnosis, mucus plugs, and poor pulmonary function are risk factors for acute exacerbation of ABPA.

Cerium-doped MIL-101-NH2(Fe) as superior adsorbent for simultaneous capture of phosphate and As(V) from Yangzonghai coastal spring water.

A series of novel cerium-doped MIL-101-NH2 materials were synthesized using the solvothermal method for the simultaneous efficient removal of phosphate and As(V). According to the characterization results, cerium was successfully loaded onto MIL-101-NH2 and that Ce-MOFs might be generated during the loading process, which modified the crystal structure of MIL-101-NH2 and resulted in MOFs with different microstructures. In single-uptake systems containing only phosphate or As(V), isothermal adsorption experiments showed that 1Ce-MIL-101-NH2 exhibited better adsorption properties of phosphate and As(V) than MIL-101-NH2. Furthermore, the uptake amounts of phosphate and As(V) reached 341.5 mg/g and 249 mg/g, respectively. Superior uptake amounts for binary phosphate (167.36 mg/g) and As(V) (87.55 mg/g) were achieved with 1Ce-MIL-101-NH2. Kinetic experiments revealed a higher uptake rate of phosphate than of As(V). FT-IR and XPS analyses showed that the main mechanism for the removal of phosphate and As(V) from water by 1Ce-MIL-101-NH2 was the formation of an Fe/CeOP inner complex through ligand complexation and electrostatic attraction. Furthermore, 1Ce-MIL-101-NH2 exhibited high selectivity and excellent efficiency in removing phosphate and As(V) in contaminated spring water in the presence of competing anions; this further confirms the application potential of the novel adsorbent.

High-performance lanthanum-based metal-organic framework with ligand tuning of the microstructures for removal of fluoride from water.

Excess fluoride in water poses a threat to ecology and human health, which has attracted global attention. In this study, a series of lanthanum-based metal-organic frameworks (La-MOFs) were synthesized by varying the organic ligands (i.e., terephthalic acid (BDC), trimesic acid (BTC), biphenyl-4,4-dicarboxylic acid (BPDC), 2,5-dihydroxyterephthalic acid (BHTA), and 1,2,4,5-benzenetetracarboxylic acid (PMA)) to control the microscopic structure of the MOFs and subsequently apply them for the removal of fluoride in water. The maximum capture capacities of La-BTC, La-BPDC, La-BHTA, La-PMA, and La-BDC at 298 K are 105.2, 125.9, 145.5, 158.9, and 171.7 mg g-1, respectively. The adsorption capacity is greater than most reported adsorbents. The adsorption isotherms of La-MOFs for fluoride are well fit to the Langmuir isotherm model. In addition, the adsorption kinetics of La-BTC, La-BPDC, La-BHTA, La-PMA, and La-BDC follows the pseudo-second-order kinetic model, and the kinetic rate-limiting step of adsorption is chemical adsorption. Thermodynamics revealed that temperature is favorable for the adsorption of fluoride. Meanwhile, La-BTC, La-BPDC, La-BHTA, La-PMA, and La-BDC are suitable for the removal of fluoride in a relatively wide pH range (4.0-9.0). Simultaneously, from X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) analysis, electrostatic attraction and ligand exchange are identified as the main action mechanisms for the adsorption of fluoride of La-MOFs. The prepared La-MOFs are used as efficient adsorbents for removal of fluoride in actual water, indicating that they have great potential in removing fluoride in real and complex environmental water. This work provides a new strategy for designing adsorbents with adjustable microstructure and expected function to effectively recover fluorosis in water.

SERPINB10 contributes to asthma by inhibiting the apoptosis of allergenic Th2 cells.

BACKGROUND: Serine peptidase inhibitor, clade B, member 10 (SERPINB10) contributes to allergic inflammation in asthma. However, its role in the T-helper type 2 (Th2) response of allergic asthma is not known. The goal of this study was to unveil the function of SERPINB10 in the Th2 response of allergic asthma and the mechanism by which SERPINB10 affects the viability of Th2 cells. METHODS: Th2 cytokines and serum levels of house dust mite (HDM)-specific IgE in bronchoalveolar lavage fluid were examined by ELISA in an HDM-induced asthma model. The number and apoptosis of Th1 and Th2 cells in mouse lungs were measured by flow cytometry. Naïve CD4 T cells from patients with asthma were cultured under appropriate polarizing conditions to generate Th1 and Th2 cells. SERPINB10 expression in polarized Th1 and Th2 cells was quantified by real-time reverse transcription-quantitative polymerase chain reaction. SERPINB10 expression was knocked down in human CD4 T cells with lentivirus. RESULTS: Knockdown of SERPINB10 expression significantly diminished HDM-induced Th2 cytokine secretion and level of HDM-specific IgE. After HDM exposure, SERPINB10-knockdown mice had diminished numbers of Th2 cells, but similar numbers of Th1 cells, compared with those in negative-control mice. Th2 cells of SERPINB10-knockdown mice were more susceptible to apoptosis than that of control mice. Stimulating T-cell receptors (TCRs) with anti-CD3 antibody caused upregulation of SERPINB10 expression in polarized Th2 cells, but not polarized Th1 cells. Knockdown of SERPINB10 expression resulted in fewer numbers and greater apoptosis of polarized Th2 cells. CONCLUSION: Our results suggest that SERPINB10 may contribute to allergic inflammation and the Th2 response of asthma by inhibiting the apoptosis of Th2 cells.

Small Proline-Rich Protein 3 Regulates IL-33/ILC2 Axis to Promote Allergic Airway Inflammation.

Small proline-rich proteins (SPRRs), components of cornified cell envelope precursors, have recently been found to participate in airway diseases. However, their role in allergic airway inflammatory conditions remains unknown. Here, we explored the expression of SPRR3 in house dust mite (HDM)-sensitized/challenged mice and attempted to elucidate the regulatory role of SPRR3 in allergic airway inflammation. SPRR3 was identified via bioinformatics analysis of Gene Expression Omnibus (GEO) databases and further confirmed to be upregulated in the lungs of asthmatic mice. Knockdown of SPRR3 via the intratracheal route significantly inhibited eosinophils in bronchoalveolar lavage fluid (BALF) and suppressed the expressions of type 2 cytokines (IL-4, IL-5, and IL-13) in BALF and lung tissues. Further, SPRR3 knockdown reduced the expression of IL-33 and further attenuated the activation of the PI3K/AKT/NF-κB signaling pathway in the recruitment of group 2 innate lymphoid cells (ILC2s) to inhibit allergic airway inflammation. In vitro, SPRR3 siRNA could alleviate HDM-induced inflammatory responses in BEAS-2B cells. This study reveals the regulatory role of SPRR3 in allergic airway inflammation, identifying this protein as a potential novel therapeutic target for asthma.

Possible Novel Therapeutic Targets in Lymphangioleiomyomatosis Treatment.

Lymphangioleiomyomatosis (LAM) is a rare systemic neoplastic disease that exclusively happens in women. Studies focusing on LAM and tuberous sclerosis complex (TSC) have made great progress in understanding the pathogenesis and searching for treatment. The inactive mutation of TSC1 or TSC2 is found in patients with LAM to activate the crucial mammalian target of rapamycin (mTOR) signaling pathway and result in enhanced cell proliferation and migration. However, it does not explain every step of tumorigenesis in LAM. Because cessation of rapamycin would break the stabilization of lung function or improved quality of life and lead to disease recurrent, continued studies on the pathogenesis of LAM are necessary to identify novel targets and new treatment. Researchers have found several aberrant regulations that affect the mTOR pathway such as its upstream or downstream molecules and compensatory pathways in LAM. Some therapeutic targets have been under study in clinical trials. New methods like genome-wide association studies have located a novel gene related to LAM. Herein, we review the current knowledge regarding pathogenesis and treatment of LAM and summarize novel targets of therapeutic potential recently.

Testosterone antagonizes paraquat-induced cardiomyocyte senescence via the mIGF-1/SIRT1 signaling pathway.

Testosterone has been demonstrated to antagonize doxorubicin-induced cardiomyocyte senescence. However, whether testosterone prevents the paraquat-induced cardiomyocyte senescence is largely unknown. The detection of SA-ß-gal activity was performed using senescence ß-gal staining kit and the reactive oxygen species levels were determined by reactive oxygen species assay kit. The plasmids for insulin-like growth factor 1 shRNA (sh-mIGF-1), sirtuin-1 shRNA (sh-SIRT1), scramble shRNA (sh-NC), overexpressing mIGF-1 (mIGF-1), overexpressing SIRT1 (SIRT1), and negative controls (NC) were obtained for this study. The expression of target genes was detected using quantitative real-time PCR, immunolabeling, and western blot. We found that testosterone significantly delayed the paraquat-induced HL-1 cardiomyocyte senescence as evidenced by decreasing senescence-associated ß-galactosidase activity and reactive oxygen species generation, which were accompanied by the up-regulated expression of mIGF-1 and SIRT1. RNA interference to reduce mIGF-1 and SIRT1 expression showed that testosterone prevented paraquat-induced HL-1 senescence via the mIGF-1/SIRT1 signaling pathway. Furthermore, myocardial contraction was evaluated by expression of genes of the contractile proteins/enzymes, such as α-myosin heavy chain 6 (MHC6), α-myosin heavy chain 7 (MHC7), α-skeletal actin (ACTA-1), and sarco/endoplasmic reticulum calcium ATPase-2 (SERCA2). Testosterone adjusted the above four gene expressions and the adjustment was blocked by mIGF-1 or SIRT1 inhibition. Our findings suggested that the mIGF-1/SIRT1 signaling pathway mediated the protective function of testosterone against the HL-1 cardiomyocyte senescence by paraquat, which provided new clues for the mechanisms underlying the anti-aging role of testosterone in cardiomyocytes.