Fusion Genes Landscape of Lung Cancer Patients From Inner Mongolia, China.

Lung cancer is the leading cause of cancer-related deaths globally. Gene fusion, a key driver of tumorigenesis, has led to the identification of numerous driver gene fusions for lung cancer diagnosis and treatment. However, previous studies focused on Western populations, leaving the possibility of unrecognized lung cancer-associated gene fusions specific to Inner Mongolia due to its unique genetic background and dietary habits. To address this, we conducted DNA sequencing analysis on tumor and adjacent nontumor tissues from 1200 individuals with lung cancer in Inner Mongolia. Our analysis established a comprehensive fusion gene landscape specific to lung cancer in Inner Mongolia, shedding light on potential region-specific molecular mechanisms underlying the disease. Compared to Western cohorts, we observed a higher occurrence of ALK and RET fusions in Inner Mongolian patients. Additionally, we discovered eight novel fusion genes in three patients: SLC34A2-EPHB1, CCT6P3-GSTP1, BARHL2-APC, HRAS-MELK, FAM134B-ERBB2, ABCB1-GIPC1, GPR98-ALK, and FAM134B-SALL1. These previously unreported fusion genes suggest potential regional specificity. Furthermore, we characterized the fusion genes' structures based on breakpoints and described their impact on major functional gene domains. Importantly, the identified novel fusion genes exhibited significant clinical and pathological relevance. Notably, patients with SLC34A2-EPHB1, CCT6P3-GSTP1, and BARHL2-APC fusions showed sensitivity to the combination of chemotherapy and immunotherapy. Patients with HRAS-MELK, FAM134B-ERBB2, and ABCB1-GIPC1 fusions showed sensitivity to chemotherapy. In summary, our study provides novel insights into the frequency, distribution, and characteristics of specific fusion genes, offering valuable guidance for the development of effective clinical treatments, particularly in Inner Mongolia.

Temperature-Insensitive Nonpolar Suspensions of Polyoxyethylene Alkyl Ether-Grafted Silica Nanoparticles.

Nonpolar suspensions of organically modified particles exhibit a strong temperature sensitivity owing to the high-temperature-induced desorption/decomposition and the low-temperature-induced disorder/order conformational transition of the modifiers. This strong temperature sensitivity limits their applications, such as lubricants and oil-based drilling fluids, which require the suspensions to operate over a wide temperature range (e.g., 0-200 °C). We hypothesize that the introduction of a flexible ethylene oxide (EO) chain into the modifiers can disrupt the low-temperature-induced ordered conformation to improve the stability of the nonpolar suspensions. In this article, nonpolar suspensions with temperature insensitivity in the range of 5-160 °C were obtained via the covalent modification of silica NPs and the introduction of EO chains into the modifier molecules. Here, octadecyl-grafted silica NPs (C18-SiO2) and polyoxyethylene alkyl ether-grafted silica NPs (AEOn-SiO2) were synthesized and subsequently dispersed in mineral oil. The rheological properties of each suspension at different temperatures were evaluated, and the thermal stability of AEOn-SiO2 in mineral oil was investigated along with the conformational changes of the grafted chains. In the temperature range of 5-160 °C, the apparent viscosity and gel strength of the C18-SiO2 suspension changed dramatically, whereas the AEOn-SiO2 suspensions exhibited constant rheological properties over this temperature range. This temperature insensitivity of AEOn-SiO2 suspensions is attributed to the excellent thermal stability of AEOn-SiO2 in mineral oil and the disordered conformation of the EO chains upon cooling. This study provides a novel approach to preparing temperature-insensitive nonpolar suspensions, which have potential applications in the petroleum and lubricant industries.

Nanoemulsions Stable against Ostwald Ripening.

Ostwald ripening, the dominant mechanism of droplet size growth for an O/W nanoemulsion at high surfactant concentrations, depends on micelles in the water phase and high aqueous solubility of oil, especially for spontaneously formed nanoemulsions. In our study, O/W nanoemulsions were formed spontaneously by mixing a water phase with an oil phase containing fatty alcohol polyoxypropylene polyoxyethylene ether (APE). By monitoring periodically the droplet size of the nanoemulsions via dynamic light scattering, we demonstrated that the formed O/W nanoemulsions are stable against Ostwald ripening, i.e., droplet growth. In contrast, the nanoemulsion droplets grew with the addition of micelles, demonstrating the pivotal role of the presence of micelles in the water phase in the occurrence of Ostwald ripening. The influence of the initial phase of APE, the oil or water phase in which APE is present, on the micelle formation is discussed by the partition coefficient and interfacial adsorption of APE between the oil and water phase using a surface and interfacial tensiometer. In addition, the spontaneously formed O/W nanoemulsion, which is stable against Ostwald ripening, can be used as a nanocarrier for the delivery of water-insoluble pesticides. These results provide a novel approach for the preparation of stable nanoemulsions and contribute to elucidating the mechanism of instability of nanoemulsions.

Identification of cough-variant asthma phenotypes based on clinical and pathophysiologic data.

BACKGROUND: Cough-variant asthma (CVA) may respond differently to antiasthmatic treatment. There are limited data on the heterogeneity of CVA. OBJECTIVE: We aimed to classify patients with CVA using cluster analysis based on clinicophysiologic parameters and to unveil the underlying molecular pathways of these phenotypes with transcriptomic data of sputum cells. METHODS: We applied k-mean clustering to 342 newly physician-diagnosed patients with CVA from a prospective multicenter observational cohort using 10 prespecified baseline clinical and pathophysiologic variables. The clusters were compared according to clinical features, treatment response, and sputum transcriptomic data. RESULTS: Three stable CVA clusters were identified. Cluster 1 (n = 176) was characterized by female predominance, late onset, normal lung function, and a low proportion of complete resolution of cough (60.8%) after antiasthmatic treatment. Patients in cluster 2 (n = 105) presented with young, nocturnal cough, atopy, high type 2 inflammation, and a high proportion of complete resolution of cough (73.3%) with a highly upregulated coexpression gene network that related to type 2 immunity. Patients in cluster 3 (n = 61) had high body mass index, long disease duration, family history of asthma, low lung function, and low proportion of complete resolution of cough (54.1%). TH17 immunity and type 2 immunity coexpression gene networks were both upregulated in clusters 1 and 3. CONCLUSION: Three clusters of CVA were identified with different clinical, pathophysiologic, and transcriptomic features and responses to antiasthmatics treatment, which may improve our understanding of pathogenesis and help clinicians develop individualized cough treatment in asthma.

Low-Dose Taxol Promotes Neuronal Axons Extension and Functional Recovery after Spinal Cord Injury.

Axonal regeneration has been the research focus in the field of clinical treatment for spinal cord injury (SCI). The growth and extension of neuronal axons is a dynamic biological process mediated by the cytoskeleton, and microtubule plays an important role in axonal growth. Moderate stabilization of microtubule promotes axonal growth and eliminates various intra- and extracellular mechanisms that impede axonal regeneration. After SCI, the damaged axons rapidly form a growth cone, wherein the stability of tubulin decreases, impairing axonal regeneration. Taxol with proven clinical safety is commonly used as a broad-spectrum antitumor drug. Importantly, Taxol can promote axonal extension by enhancing and stabilizing the microtubule assembly. In our study, we systematically investigated the differentiation of neural stem cells (NSCs) in vitro and functional recovery in injured rats in vivo following Taxol treatment. Low-dose Taxol promoted differentiation of NSCs to neurons and significantly extended the axons in vitro. In vivo, Taxol promoted the expression of ßIII-tubulin in the injured areas and motor function recovery after SCI. Low-dose Taxol is a promising clinical agent to promote axonal regeneration after SCI.

Bone morphogenetic protein 4 inhibits pulmonary fibrosis by modulating cellular senescence and mitophagy in lung fibroblasts.

BACKGROUND: Accumulation of myofibroblasts is critical to fibrogenesis in idiopathic pulmonary fibrosis (IPF). Senescence and insufficient mitophagy in fibroblasts contribute to their differentiation into myofibroblasts, thereby promoting the development of lung fibrosis. Bone morphogenetic protein 4 (BMP4), a multifunctional growth factor, is essential for the early stage of lung development; however, the role of BMP4 in modulating lung fibrosis remains unknown. METHODS: The aim of this study was to evaluate the role of BMP4 in lung fibrosis using BMP4-haplodeleted mice, BMP4-overexpressed mice, primary lung fibroblasts and lung samples from patients with IPF. RESULTS: BMP4 expression was downregulated in IPF lungs and fibroblasts compared to control individuals, negatively correlated with fibrotic genes, and BMP4 decreased with transforming growth factor (TGF)-ß1 stimulation in lung fibroblasts in a time- and dose-dependent manner. In mice challenged with bleomycin, BMP4 haploinsufficiency perpetuated activation of lung myofibroblasts and caused accelerated lung function decline, severe fibrosis and mortality. BMP4 overexpression using adeno-associated virus 9 vectors showed preventative and therapeutic efficacy against lung fibrosis. In vitro, BMP4 attenuated TGF-ß1-induced fibroblast-to-myofibroblast differentiation and extracellular matrix (ECM) production by reducing impaired mitophagy and cellular senescence in lung fibroblasts. Pink1 silencing by short-hairpin RNA transfection abolished the ability of BMP4 to reverse the TGF-ß1-induced myofibroblast differentiation and ECM production, indicating dependence on Pink1-mediated mitophagy. Moreover, the inhibitory effect of BMP4 on fibroblast activation and differentiation was accompanied with an activation of Smad1/5/9 signalling and suppression of TGF-ß1-mediated Smad2/3 signalling in vivo and in vitro. CONCLUSION: Strategies for enhancing BMP4 signalling may represent an effective treatment for pulmonary fibrosis.

Associations between comorbidities and annual incidence plus frequency of asthma exacerbation hospitalisation during the past year: data from CARN study.

PURPOSE: While asthma comorbidities are associated with higher health care utilisation, lower quality of life and poorer asthma control, the impact of asthma comorbidities on hospitalisation for asthma exacerbation (H-AX) remains less recognised. We aim to analyse the impact of asthma comorbidities on H-AX. METHODS: Based on a national survey on asthma control and disease perception (CARN 2015 study), we analysed the impact of comorbidities on annual incidence and frequency of H-AX in China. Information on demographic characteristics, asthma comorbidities and annual incidence and frequency of H-AX were presented in this study. RESULTS: Among 3875 ambulatory asthma patients, 75.9% (2941/3875) had comorbidities, and 26.4% (1017/3858) experienced H-AX during past year. After adjusting for confounding factors such as demographic data, smoking status and asthma control, COPD [OR = 2.189, 95% CI (1.673, 2.863)] and coronary heart disease [OR = 1.387, 95% CI (1.032, 1.864)] were associated with higher annual incidence, while allergic rhinitis [OR = 0.692, 95% CI (0.588, 0.815)] was associated with lower annual incidence, of H-AX. In terms of frequency, allergic rhinitis [OR = 1.630, 95% CI (1.214, 2.187)], COPD [OR = 1.472, 95% CI (1.021, 2.122)] and anxiety [OR = 2.609, 95% CI (1.051, 6.477)] showed statistically significant correlation with frequent H-AX. CONCLUSIONS: COPD and coronary heart disease were associated with higher annual incidence, while allergic rhinitis was associated with lower annual incidence of H-AX. Allergic rhinitis, COPD and anxiety were associated with frequent H-AX. Comorbidities may have an important role in the risk and frequency of annual hospitalisations due to asthma exacerbation. The goal of asthma control should rely on a multi-disciplinary treatment protocol.

Association of VEGFA polymorphisms with chronic obstructive pulmonary disease in Chinese Han and Mongolian populations.

NEW FINDINGS: What is the central question of this study? Vascular endothelial growth factor A (VEGFA) is an important growth factor involved in changes in the bronchial microvascular and airway inflammation in chronic obstructive pulmonary disease (COPD) progression. What is the association of single nucleotide polymorphisms (SNPs) in VEGFA with the risk of COPD in the Chinese Han and Mongolian populations? What is the main finding and its importance? The effect of five SNPs in the VEGFA gene was analysed and compared between the Chinese Han and Mongolian populations. A contribution of risk alleles rs833068, rs833070 and rs3024997 to COPD was detected in the Chinese Mongolian population only. The study provided data from different populations to validate the role of VEGFA polymorphisms in COPD and provided reliable SNPs to predict the risk of COPD. ABSTRACT: We attempted to define the associations between single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGFA) gene and chronic obstructive pulmonary disease (COPD) in Chinese Han and Mongolian cohorts. Five SNPs were genotyped in cohorts of 684 COPD patients (350 Mongolian and 334 Han) and 784 healthy controls (350 Mongolian and 434 Han) using SNPscan multiplex PCR. SNP frequencies, genetic models and haplotypes were analysed using the chi-square test. The associations of SNPs with COPD and linkage disequilibrium were analysed using logistic regression and HaploView, respectively. We found that only rs833068G>A, rs833070T>C and rs3024997G>A were significantly associated with the risk of COPD in the Mongolian population (rs833068: P < 0.001, rs833070: P < 0.001, rs3024997: P = 0.002). In the analysis of genotype distributions, the A/A and G/A genotypes in rs833068 (A/A: odds ratio (OR) = 0.313, P < 0.001; G/A: OR = 0.724, P < 0.001) and rs3024997 (A/A: OR = 0.513, P = 0.008; G/A: OR = 0.671, P = 0.008) and the C/C and T/C genotypes in rs833070 (C/C: OR = 0.435, P = 0.007; T/C: OR = 0.593, P = 0.007) were associated with protection against COPD in the Mongolian population. The haplotype frequencies of GCCAT and GTCGC were significantly different between the patients and controls (GCCAT: P = 0.001; GTCGC: P < 0.001) in the Mongolian population. Our findings indicate that five SNPs in the VEGFA gene play divergent roles in the Han and Mongolian populations. rs833068A, rs833070C and rs3024997A were observed to be associated with the risk of COPD in the Mongolian population.

Pulmonary surfactant-associated protein B regulates prostaglandin-endoperoxide synthase-2 and inflammation in chronic obstructive pulmonary disease.

NEW FINDINGS: What is the central question of this study? It is reported that polymorphism of the gene for pulmonary surfactant-associated protein B (SFTPB) is associated with chronic obstructive pulmonary disease (COPD): what are the function and mechanism of action of SFTPB in COPD? What is the main finding and its importance? Under stimulation of the risk factors of COPD, SFTPB expression is decreased, which may be involved in the formation of COPD. The progress of COPD induces an inflammatory response and reduces SFTPB expression. Levels of prostaglandin-endoperoxide synthase-2 (PTGS2) and inflammatory responses are changed by SFTPB, which indicates that SFTPB promotes the progression of COPD by PTGS2 and inflammation. ABSTRACT: Pulmonary surfactant-associated protein B (SFTPB) is a critical protein for lung homeostasis, and polymorphism of its gene is associated with chronic obstructive pulmonary disease (COPD). However, few studies have so far confirmed the functional involvement of SFTPB in COPD. Serum SFTPB and inflammatory cytokine levels were measured in 54 patients with acute exacerbation of COPD and 29 healthy controls. A549 cells were induced using 10% cigarette smoke extract (CSE) and treated with dexamethasone to investigate the effect of inflammation on SFTPB expression, and the effect of SFTPB overexpression and silencing on inflammatory cytokines was measured using real-time PCR and enzyme-linked immunosorbent assay. SFTPB expression was assessed in mouse lung tissues using immunofluorescence. Serum levels of SFTPB were significantly lower in COPD patients than in controls (P = 0.009). Conversely, levels of interleukin (IL)-6 and prostaglandin-endoperoxide synthase-2 (PTGS2) were increased in COPD patients (IL-6: P = 0.006; PTGS2: P = 0.043). After CSE treatment, SFTPB mRNA and protein levels were significantly decreased compared to controls (mRNA: P = 0.002; protein: P = 0.011), while IL-6, IL-8 and PTGS2 were elevated. Dexamethasone treatment increased SFTPB levels. Following overexpression of SFTPB in A549 cells, mRNA and protein levels of IL-6, IL-8 and PTGS2 were significantly reduced, while gene silencing induced the opposite effect. SFTPB levels were significantly reduced in the lung tissue of a mouse model of COPD compared to controls. Reduced SFTPB levels may induce PTGS2 and inflammatory responses in COPD and SFTPB could be a key protein for evaluation of COPD progression.

Origin of Rebound Suppression for Dilute Polymer Solution Droplets on Superhydrophobic Substrate.

Controlling droplet deposition with a minute amount of polymer additives is of profound practical importance in a wild range of applications. Previous work ascribed the relevant mechanisms to extensional viscosity, normal stress, wetting properties, etc., but the mechanism remains controversial. In this paper, we employ molecular dynamics simulations systematically for the first time to investigate the origin of rebound suppression for dilute polymer solution droplets on a flat superhydrophobic substrate. The results demonstrate that polymer-substrate interactions and impact velocities dominate the antirebound phenomenon. For low impact velocities, the dynamic characteristics of droplets are insensitive to polymer additives. However, large impact velocities will enhance the stretch behavior of polymer chains and make the chains closer to the substrate, increasing the probability of polymer molecules contacting the bottom substrate. With the cooperation of strong polymer-substrate interactions, polymer molecules can be absorbed easily by the bottom substrate, resisting the retraction process and leading to the onset of the antirebound behavior.

Dynamic Covalent Nanoparticles for Acid-Responsive Nonaqueous Pickering Emulsions.

Acid-responsive nonaqueous (glycerol in n-decane) Pickering emulsions were prepared using preferentially oil-wetted dynamic covalent silica (SiO2-pDB) nanoparticles as the Pickering emulsifiers. The acid-responsive Pickering emulsifier SiO2-pDB was prepared based on a Schiff base reaction between amino silica (SiO2-NH2) and p-decanoxybenzaldehyde (pDBA). The formation of SiO2-pDB was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and elemental analysis. The preferentially oil-wetted character of SiO2-pDB was indicated by contact angle measurement. Stable nonaqueous Pickering emulsions were prepared using preferentially oil-wetted SiO2-pDB as the Pickering emulsifier. However, after adjusting the nonaqueous Pickering emulsions to an acidic environment, complete phase separation occurred. In the acidic environment, preferentially oil-wetted SiO2-pDB decomposed into hydrophilic SiO2-NH2 and hydrophobic pDBA due to the decomposition of the dynamic imine bond in the SiO2-pDB. Then, the hydrophilic SiO2-NH2 and hydrophobic pDBA desorbed from the two-phase interface, resulting in complete phase separation of the initially stable nonaqueous Pickering emulsions. The acid-responsive nonaqueous Pickering emulsions show great potential in application in water sensitive systems, such as oil-based drilling fluids.

Effects of water-soluble components of atmospheric particulates from rare earth mining areas in China on lung cancer cell cycle.

BACKGROUND: This study aims to investigate the effects of water soluble particulate matter (WSPM) on the viability and protein expression profile of human lung adenocarcinoma cell A549 in the Bayou Obo rare earth mining area, and explore the influence of WSPM on the A549 cell cycle. RESULTS: It was found that WSPM can inhibit the viability of A549 cells and induce cell arrest in the G2/M phase. Compared with controls, exposure to WSPM10 and WSPM2.5 induced 134 and 116 proteins to be differentially expressed in A549 cells, respectively. In addition, 33 and 31 differentially expressed proteins were further confirmed, and was consistent with the proteomic analysis. The most prominent enrichment in ribosome-associated proteins were presented. When RPL6, RPL13, or RPL18A gene expression was inhibited, A549 cells were arrested in the G1 phase, affecting the expression of Cyclin D1, p21, RB1, Cyclin A2, Cyclin B1, CDC25A, CDK2, CHEK2 and E2F1. Furthermore, the La3+, Ce3+, Nd3+ and F- in WSPM also inhibited the viability of A549 cells. After 24 h of exposure to 2 mM of NaF, A549 cells were also arrested in the G2/M phase, while the other three compounds did not have this effect. These four compounds affected the cell cycle regulatory factors in A549 cells, mainly focusing on effecting the expression of CDK2, CDK4, RB1, ATM, TP53 and MDM2 genes. These results are consistent with the those from WSPM exposure. CONCLUSIONS: These results revealed that WSPM from rare earth mines decreased the viability of A549 cells, and induced cell cycle G2/M phase arrest, and even apoptosis, which may be independent of the NF-κB/MYD88 pathway, and be perceived by the TLR4 receptor. The dysfunction of the cell cycle is correlated to the down-expression of ribosomal proteins (RPs). However, it is not the direct reason for the A549 cell arrest in the G2/M phase. La3+, Ce3+, and F- are probably the main toxic substances in WSPM, and may be regulate the A549 cell cycle by affecting the expression of genes, such as MDM2, RB1, ATM, TP53, E2F1, CDK2 and CDK4. These results indicate the importance for further research into the relationship between APM and lung cancer.

Evaluation of Chitosan Derivatives Modified Mesoporous Silica Nanoparticles as Delivery Carrier.

Chitosan is a non-toxic biological material, but chitosan is insoluble in water, which hinders the development and utilization of chitosan. Chitosan derivatives N-2-Hydroxypropyl trimethyl ammonium chloride (N-2-HACC) and carboxymethyl chitosan (CMCS) with good water solubility were synthesized by our laboratory. In this study, we synthesized mesoporous SiO2 nanoparticles by the emulsion, and then the mesoporous SiO2 nanoparticles were modified with γ-aminopropyltriethoxysilane to synthesize aminated mesoporous SiO2 nanoparticles; CMCS and N-2-HACC was used to cross-link the aminated mesoporous SiO2 nanoparticles to construct SiO2@CMCS-N-2-HACC nanoparticles. Because the aminated mesoporous SiO2 nanoparticles with positively charged can react with the mucous membranes, the virus enters the body mainly through mucous membranes, so Newcastle disease virus (NDV) was selected as the model drug to evaluate the performance of the SiO2@CMCS-N-2-HACC nanoparticles. We prepared the SiO2@CMCS-N-2-HACC nanoparticles loaded with inactivated NDV (NDV/SiO2@CMCS-N-2-HACC). The SiO2@CMCS-N-2-HACC nanoparticles as delivery carrier had high loading capacity, low cytotoxicity, good acid resistance and bile resistance and enteric solubility, and the structure of NDV protein encapsulated in the nano vaccine was not destroyed. In addition, the SiO2@CMCS-N-2-HACC nanoparticles could sustain slowly released NDV. Therefore, the SiO2@CMCS-N-2-HACC nanoparticles have the potential to be served as delivery vehicle for vaccine and/or drug.

Transplantation of Mesenchymal Stem Cells Attenuates Pulmonary Hypertension by Normalizing the Endothelial-to-Mesenchymal Transition.

For decades, stem cell therapies for pulmonary hypertension (PH) have progressed from laboratory hypothesis to clinical practice. Promising preclinical investigations have laid both a theoretical and practical foundation for clinical application of mesenchymal stem cells (MSCs) for PH therapy. However, the underlying mechanisms are still poorly understood. We sought to study the effects and mechanisms of MSCs on the treatment of PH. For in vivo experiments, the transplanted GFP+ MSCs were traced at different time points in the lung tissue of a chronic hypoxia-induced PH (CHPH) rat model. The effects of MSCs on PH pathogenesis were evaluated in both CHPH and sugen hypoxia-induced PH models. For in vitro experiments, primary pulmonary microvascular endothelial cells were cultured and treated with the MSC conditioned medium. The specific markers of endothelial-to-mesenchymal transition (EndMT) and cell migration properties were measured. MSCs decreased pulmonary arterial pressure and ameliorated the collagen deposition, and reduced the thickening and muscularization in both CHPH and sugen hypoxia-induced PH rat models. Then, MSCs significantly attenuated the hypoxia-induced EndMT in both the lungs of PH models and primary cultured rat pulmonary microvascular endothelial cells, as reflected by increased mesenchymal cell markers (fibronectin 1 and vimentin) and decreased endothelial cell markers (vascular endothelial cadherin and platelet endothelial cell adhesion molecule-1). Moreover, MSCs also markedly inhibited the protein expression and degradation of hypoxia-inducible factor-2α, which is known to trigger EndMT progression. Our data suggest that MSCs successfully prevent PH by ameliorating pulmonary vascular remodeling, inflammation, and EndMT. Transplantation of MSCs could potentially be a powerful therapeutic approach against PH.

BRIP1 rs10744996C>A variant increases the risk of chronic obstructive pulmonary disease in the Mongolian population of northern China.

NEW FINDINGS: What is the central question of this study? What is the role of breast cancer type 1 interacting protein C-terminal helicase 1 (BRIP1) polymorphism in chronic obstructive pulmonary disease (COPD)? What is the main finding and its importance? Variant rs10744996C>A of BRIP1 increases the susceptibility of the Mongolian population to COPD. The expression of BRIP1 was significantly reduced in cigarette smoke extract-treated airway epithelial cells. ABSTRACT: Cigarette smoke is a major environmental pollutant that can induce DNA damage in humans. The development and progression of chronic obstructive pulmonary disease (COPD) are known to be related to the impairment of DNA repair. Breast cancer type 1 interacting protein C-terminal helicase 1 (BRIP1) plays an important role in DNA interstrand crosslink repair and double-strand break repair. However, the role of BRIP1 polymorphisms in COPD has not been previously described. In this study, whole genome sequencing was used to identify mutations, and single nucleotide polymorphism (SNP) genotyping was used to verify the selected SNPs. In addition the BRIP1 expression levels in 16HBE and A549 airway epithelial cells treated with or without cigarette smoke extract (CSE) were measured using western blotting and RT-qPCR. Rs10744996C>A in the 3'-untranslated region (3'UTR) of BRIP1 was then genotyped in 1296 COPD cases and 988 healthy control subjects from a Mongolian population in northern China. Significant differences in the distribution of rs10744996C>A variants between COPD and control groups (P = 0.001) were identified. Rs10744996C>A was found to be associated with significantly increased COPD risk (adjusted odds ratio = 1.60, 95% CI = 1.30-1.98, P < 0.0001). Additionally, rs10744996A genotype was found to interact with a family history of cancer and a history of x-ray exposure (P = 0.028 and 0.009, respectively). BRIP1 expression levels in 16HBE and A549 cells treated with CSE were significantly lower compared to the control treated cells. The rs10744996C>A variant of BRIP1 increased the COPD susceptibility of the Mongolian population cohort. BRIP1 mRNA and protein expression levels were significantly reduced in conjunction with CSE-induced DNA damage in 16HBE and A549 cells.

Temperature and CO2 Dual-Responsive Pickering Emulsions Using Jeffamine M2005-Modified Cellulose Nanocrystals.

Cellulose nanocrystals (CNCs) with excellent biodegradability are promising biomaterials for use as responsive Pickering emulsifiers. However, the high hydrophilicity of CNCs limits their emulsification ability. Some existing studies have utilized complicated covalent modification procedures to increase the hydrophobicity of CNCs. To simplify the modification process, we prepared hydrophobically modified CNCs (CNCs-M2005) via simple and controllable electrostatic interactions with thermosensitive M2005. The obtained CNCs-M2005 exhibited temperature and CO2 dual-responsive properties. Subsequently, stable oil/water Pickering emulsions were prepared using the partially hydrophobic CNCs-M2005 at 20 °C. However, demulsification occurred when the temperature increased to 60 °C. This temperature-induced demulsification resulted from the dehydration of polyethylene oxide and polypropylene oxide, causing the aggregation of the CNCs-M2005, as shown by dynamic light scattering and transmission electron microscopy experiments. In addition, demulsification was also achieved after bubbling CO2, which was attributed to the dissociation of the partially hydrophobic CNCs-M2005. The temperature and CO2 dual-responsive biosafe Pickering emulsions open up opportunity for the design of intelligent food, cosmetic, and drug delivery systems.

Independent Clinical Factors Relevant to Prognosis of Patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND The prognosis of idiopathic pulmonary fibrosis (IPF) is the worst among all interstitial lung diseases, and is related to the disease itself. Comorbidities or complications can worsen IPF. We assessed the effect of comorbidities on the survival of IPF patients. A retrospective review of patients with IPF was completed. MATERIAL AND METHODS Information on demographic features, clinical examination, and comorbidities at baseline were obtained. Then, median, 1-year, and 5-year survival was calculated. A total of 380 patients with IPF admitted to Beijing Chao-Yang Hospital from 1 April 2002 to 31 March 2015 were followed up until December 2016. RESULTS Of these 380 patients, 71.9% died during the study period. Median survival was 2.25 years and overall 5-year survival was 28.5%. Also, 86.3% of patients were males. A total of 248 cases underwent lung function tests, and 178 patients underwent bronchoalveolar lavage (BAL). Multivariate analyses showed that forced expiratory volume in 1 second/forced vital capacity (FVC), diffusing capacity of the lungs for carbon monoxide percent predicted, FVC% predicted, the number of macrophages, neutrophils, and lymphocytes in BAL fluid, pulmonary hypertension, hypoxemia, and hydropower disorder were independent prognostic indicators of IPF, GAP gender (G), age (A), and 2 pulmonary physiological parameters (P) model can help to predict prognosis of IPF. CONCLUSIONS Spirometry, GAP model, and BAL are helpful to forecast the prognosis of IPF. IPF patients also suffering from pulmonary arterial hypertension, hypoxemia, and hydropower disorder have a poor prognosis.

The effect characteristics of temperature on stroke mortality in Inner Mongolia and globally.

The current study investigated the correlation between stroke mortality and temperature. Monthly and seasonal variations in stroke mortality were plotted and daily stroke-related deaths were calculated. The lag times were calculated using the time series analysis. The correlation between stroke incidence and the diurnal temperature range (DTR) was analyzed using case-crossover analysis. Global stroke mortality was described in five latitudes. In the eastern region of Inner Mongolia, the stroke mortality was 174.18/105, about twice of that of the midwestern regions (87.07/105), and temperature was negatively correlated with stroke mortality. Mortality peaked in the winter and troughed in the summer (χ2 = 13.634, P < 0.001). The days in which stroke-related deaths were greater than ten occurred between late October and early April. The effect of temperature on stroke incidence occurred during a lag time of 1 (P = 0.024) or 2 months (P = 0.039). A DTR over 13 °C was positively correlated (r = 0.95, P = 0.004) with stroke with a lag time of 1 day. The effect of temperature on stroke was shown to be the same for various populations. As the latitude increases, stroke mortality also increases with latitudes > 40°; the highest mortality was 188.05/105 at the highest latitude. Only in relatively cold regions as the temperature decreases does stroke mortality increase for various populations. Differences in the time lag as well as in the DTR lag and DTR critical point vary for both the temperature and region.

Targeted delivery of immuno-RNase may improve cancer therapy.

BACKGROUND: Immunotoxins are typical therapeutic drugs that can target cancer cells. They exploit the affinity of specific monoclonal antibodies or ligands to cancer cells to deliver a conjugated protein toxin to target sites, thus, attacking the cancer cells. METHODS: The immuno-RNase, Onc-V3, showed the stability of Onc-V3 in the blood stream. Flow cytometry showed that apoptosis occurred in the HO-8910PM cells when treated with Onc-V3. Under the confocal microscope, the green fluorescent, FITC-Onc-V3, were located in the cytoplasm, suggesting that Onc-V3 had a function in the cytoplasm of cancer cells. Moreover, after staining by DAPI, the blue fluorescent nuclei showed shrinkage and grainy. Wound healing assay showed that high concentrations of Onc-V3 inhibited cell migration and the transwell invasion assay showed that Onc-V3 could inhibit cell invasion to the basement membrane. Western blot results showed significantly decreased PARP, procaspase-9, and procaspase-3 in Onc-V3-induced apoptosis. RESULTS: These results of the experiments in vitro had shown that the Onc-V3 could be delivered to the cancer cells accurately and it had strong cytotoxicity on high metastatic cancer cells. CONCLUSION: The specific toxicity of Onc-V3 on highly metastatic cancer cells can make it a promising anti-cancer drug by using V3 to target delivery of Onconase.

Dynamic Covalent Silica Nanoparticles for pH-Switchable Pickering Emulsions.

Dynamic covalent surfactants have been recently reported for preparation of pH-switchable emulsions [ Sun , D. Langmuir , 2017 , 33 , 3040 ]. In this study, dynamic covalent silica (SiO2-B) nanoparticles of switchable wettability were fabricated by a pH-responsive dynamic (covalent) imine bond between hydrophilic amino silica (SiO2-NH2) nanoparticles and hydrophobic benzaldehyde molecules. The properties of SiO2-B were characterized by Fourier transform infrared spectroscopy, elemental analysis, contact angle measurement, and ζ potential measurement. The hydrophilicity and hydrophobicity of SiO2-B were shown to be readily switchable by adjusting pH between 7.8 and 3.5. At pH 7.8, SiO2-B was partially hydrophobic and adsorbed at oil-water interface to stabilize O/W Pickering emulsions, which were characterized by electrical conductivity, optical microscopy, and confocal laser scanning microscopy. Upon lowering the pH to 3.5, the dynamic covalent bond is dissociated to convert partially hydrophobic SiO2-B into highly hydrophilic SiO2-NH2 and surface-inactive benzaldehyde. Both of them desorb from oil-water interface, resulting in a rapid oil-water separation of the Pickering emulsions. Alternating stabilization and phase separation of the Pickering emulsions over 3 cycles were demonstrated by adjusting the pH. The pH-switchable Pickering emulsions show great potential in application to effective oil-water separation of emulsions.