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BackgroundBoth genetic and lifestyle factors contribute to the development of asthma, but whether unfavourable lifestyle is associated with similar increases in risk of developing asthma among individuals with varying genetic risk levels remains unknown.MethodsA healthy lifestyle score was constructed using body mass index, smoking status, physical activities and dietary pattern to further categorise into ideal, intermediate and poor groups. Genetic risk of asthma was also categorised as three groups based on the tertiles of polygenic risk score established using 212 reported and verified single-nucleotide polymorphisms of European ancestry in the UK Biobank study. We examined the risk of incident asthma related with each lifestyle level in each genetic risk group by Cox regression models.ResultsFinally, 327 124 participants without baseline asthma were included, and 157 320 (48.1%) were male. During follow-up, 6238 participants (1.9%) developed asthma. Compared to ideal lifestyle in a low genetic risk group, poor lifestyle was associated with a hazard ratio of up to 3.87 (95% CI, 2.98–5.02) for developing asthma in a high genetic risk group. There was interaction between genetic risk and lifestyle, and the population-attributable fraction of lifestyle and genetic risk were 30.2% and 30.0% respectively.ConclusionIn this large contemporary population, lifestyle and genetic factors jointly play critical roles in the development of asthma, and the effect values of lifestyle on incident adult-onset asthma were greater than that of genetic risk. Our findings highlighted the necessity of a comprehensive intervention for the prevention of asthma despite the genetic risk.

This study presents the results of a comprehensive investigation of a wooden rice bucket made in the 1860s. Macroscopy aspects and microscopic structure were conducted to identify the wood species. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) were also adopted to investigate the degradation degree of the rice bucket compared with a new wood sample from the same species. The results of the microscopic identification concluded that the rice bucket was made of Chinese fir (Cunninghamia lanceolata). The XRD pattern indicated that the crystallinity degree of cellulose in the wooden rice bucket decreased to 33.2% from 38.8% (new wood). The FTIR spectra revealed that natural ageing resulted in the degradation of cellulose and hemicellulose, and the change of lignin was not obvious.

Background: Uneven body-surface thermal distribution is a manifestation of hypoperfusion and can be quantified by infrared thermography. Our aim was to investigate whether body-surface thermal inhomogeneity could accurately evaluate the severity of patients at risk of hypoperfusion. Methods: This was a prospective cohort study in which infrared thermography images were taken from unilateral legs of critically ill patients at high risk of hypoperfusion in a cardiac surgical intensive care unit. For each patient, five body-surface thermal inhomogeneity parameters, including standard deviation (SD), kurtosis, skewness, entropy, and low-temperature area rate (LTAR), were calculated. Demographic, clinical, and thermal characteristics of deceased and living patients were compared. The risk of mortality and capillary refill time (CRT) were chosen as the primary outcome and benchmarking parameter for hypoperfusion, respectively. The area under the receiver operating characteristic curve (AUROC) was used to evaluate predictive accuracy. Results: Three hundred seventy-three patients were included, and 55 (14.7%) died during hospital stay. Of inhomogeneity parameters, SD (0.738) and LTAR (0.768) had similar AUROC to CRT (0.757) for assessing mortality risk. Besides, there was a tendency for LTAR (1%-3%-7%) and SD (0.81°C-0.88°C-0.94°C) to increase in normotensive, hypotensive, and shock patients. These thermal parameters are associated with CRT, lactate, and blood pressure. The AUROC of a combined prediction incorporating three thermal inhomogeneity parameters (SD, kurtosis, and entropy) was considerably higher at 0.866. Conclusions: Body-surface thermal inhomogeneity provided a noninvasive and accurate assessment of the severity of critically ill patients at high risk of hypoperfusion.

Relieving serious non-point source pollution of nitrogen (N), phosphorus (P), and potassium (K) is an urgent task in China. It is necessary to explore the changing characteristics of chemical fertilization intensity (FI) and efficiency to provide references. A new method of 'relative productivity proportion weight', which was simpler than data envelope analysis, was proposed to construct models of fertilizer allocation efficiency (FAE) and chemical fertilizer integrated efficiency (FIE) by considering NPK multi-inputs and the grain output scale, respectively.During 1980-2014, the FIs of NPK chemical fertilizers in China showed a significant growing trend. After reaching the highest value of 339 kg haFrom 1980 until 2019, a reduction of FAE from 1 to 0.80 with an average of 0.75 was observed in China. FIE was found between 0.65 and 0.85 and had the potential of upgrading by 15-35%. Therefore, China needs to improve the fertilizer use efficiency in order to strive for negative growth of chemical fertilizer intensity and ecological agriculture construction. © 2022 Society of Chemical Industry.

Freezing stress is a major limiting factor in crop production. To increase frost-hardiness of crops via breeding, deciphering the genes conferring freezing-tolerance is vital. Potato cultivars (Solanum tuberosum) are generally freezing-sensitive, but some potato wild species are freezing-tolerant, including Solanum commersonii, Solanum malmeanum and Solanum acaule. However, the underlying molecular mechanisms conferring the freezing-tolerance to the wild species remain to be deciphered. In this study, five representative genotypes of the above-mentioned species with distinct freezing-tolerance were investigated. Comparative transcriptomics analysis showed that SaCBL1-like (calcineurin B-like protein) was upregulated substantially in all of the freezing-tolerant genotypes. Transgenic overexpression and known-down lines of SaCBL1-like were examined. SaCBL1-like was shown to confer freezing-tolerance without significantly impacting main agricultural traits. A functional mechanism analysis showed that SaCBL1-like increases the expression of the C-repeat binding factor-regulon as well as causes a prolonged higher expression of CBF1 after exposure to cold conditions. Furthermore, SaCBL1-like was found to only interact with SaCIPK3-1 (CBL-interacting protein kinase) among all apparent cold-responsive SaCIPKs. Our study identifies SaCBL1-like to play a vital role in conferring freezing tolerance in potato, which may provide a basis for a targeted potato breeding for frost-hardiness.

The coronavirus disease 2019 (COVID-19) epidemic has spread worldwide, posing a great threat to human beings. The stay-home quarantine is an effective way to reduce physical contacts and the associated COVID-19 transmission risk, which requires the support of efficient living materials (such as meats, vegetables, grain, and oil) delivery. Notably, the presence of potential infected individuals increases the COVID-19 transmission risk during the delivery. The deliveryman may be the medium through which the virus spreads among urban residents. However, traditional delivery route optimization methods don't take the virus transmission risk into account. Here, we propose a novel living material delivery route approach considering the possible COVID-19 transmission during the delivery. A complex network-based virus transmission model is developed to simulate the possible COVID-19 infection between urban residents and the deliverymen. A bi-objective model considering the COVID-19 transmission risk and the total route length is proposed and solved by the hybrid meta-heuristics integrating the adaptive large neighborhood search and simulated annealing. The experiment was conducted in Wuhan, China to assess the performance of the proposed approach. The results demonstrate that 935 vehicles will totally travel 56,424.55 km to deliver necessary living materials to 3,154 neighborhoods, with total risk [Formula: see text]. The presented approach reduces the risk of COVID-19 transmission by 67.55% compared to traditional distance-based optimization methods. The presented approach can facilitate a well response to the COVID-19 in the transportation sector.

Urban waterfront renewal, especially public space improvement, is important for regaining waterfront space vitality. However, existing studies constrained by sparse and hard-to-access data are hard to explore how changes in spatial elements during waterfront renewal would affect space vitality. Waterfront space vitality comprises social vitality represented by public behaviors and economic vitality represented by urban functional facilities. Taking the Maozhou River renewal project in China as an example, we collect spatial elements and vitality on corresponding periods in 2018 and 2020 (before and after the renewal construction) and use multiple linear regression models to assess the relationships. We find that the functional diversity (e.g., commercial and cultural facilities) and design quality (e.g., path density and the shoreline’s proximity to the water) are the two most influential spatial elements affecting space vitality during waterfront renewal. Overall, the use of two-time datasets has generated strong evidence for measuring waterfront revitalization.

Membrane dialysis is one of the membrane contactors applied to wastewater treatment. The dialysis rate of a traditional dialyzer module is restricted because the solutes transport through the membrane only by diffusion, in which the mass-transfer driving force across the membrane is the concentration gradient between the retentate and dialysate phases. A two-dimensional mathematical model of the concentric tubular dialysis-and-ultrafiltration module was developed theoretically in this study. The simulated results show that the dialysis rate improvement was significantly improved through implementing the ultrafiltration effect by introducing a trans-membrane pressure during the membrane dialysis process. The velocity profiles of the retentate and dialysate phases in the dialysis-and-ultrafiltration system were derived and expressed in terms of the stream function, which was solved numerically by the Crank–Nicolson method. A maximum dialysis rate improvement of up to twice that of the pure dialysis system (Vw=0) was obtained by employing a dialysis system with an ultrafiltration rate of Vw=2 mL/min and a constant membrane sieving coefficient of θ=1. The influences of the concentric tubular radius, ultrafiltration fluxes and membrane sieve factor on the outlet retentate concentration and mass transfer rate are also illustrated.

Background Patients receiving surgical treatment of acute type A Aortic Dissection (aTAAD) are common to suffer organ dysfunction in the intensive care unit due to overwhelming inflammation. Previous studies have revealed that glucocorticoids may reduce complications in certain patient groups, but evidence between postoperative glucocorticoids administration and improvement in organ dysfunction after aTAAD surgery are lacking. Methods This study will be an investigator-initiated, prospective, single-blind, randomized, single-center study. Subjects with confirmed diagnosis of aTAAD undergoing surgical treatment will be enrolled and 1:1 randomly assigned to receive either glucocorticoids or normal treatment. All patients in the glucocorticoids group will be given methylprednisolone intravenously for 3 days after enrollment. The primary endpoint will be the amplitude of variation of Sequential Organ Failure Assessment score on post-operative day 4 compared to baseline. Discussion The trial will explore the rationale for postoperative application of glucocorticoids in patients after aTAAD surgery. Trial registration This study has been registered on ClinicalTrials.gov (NCT04734418).

The interaction between the population and built environment is a constant topic in urban spaces and is the main driving force of urban evolution. Understanding urban population distribution and its relationship with the built environment could provide guidance for urban planning, traffic, and disaster management. Following this line of thought, this study conducted an empirical analysis in Xi’an, a rapidly developing western city in China. Well-permeated mobile phone location data were used to represent the spatiotemporal dynamics of the population, and the built environment was characterized from five perspectives—transportation, location, building, greenery, and land use—using multisource geospatial data. Finally, the dynamic heterogeneous influence of built environment factors on population distribution was examined using multiscale geographically weighted regression (MGWR). Overall, the influencing coefficients exhibited a significant dynamic changing process from a temporal perspective and simultaneously demonstrated spatial nonstationarity. Moreover, the specific findings about the influence of each built environment factor facilitate a deeper insight into dynamic population distribution and its determinants.

A multi-parental population is an innovative tool for mapping large numbers of loci and genetic modifications, particularly where they have been used for breeding and pre-breeding in crops. Frost injury is an environmental stress factor that greatly affects the growth, development, production efficiency, and geographical distribution of crops. No reported study has focused on genetic mapping and molecular marker development using diallel populations of potatoes. In this study, 23 successful cross combinations, obtained by a half diallel cross among 16 parents, including eight frost-tolerant advanced breeding lines and eight cultivars, were used to map the genetic loci for frost tolerance and to create a molecular marker-assisted selection (MAS) system. Three candidate regions related to frost tolerance on chromosomes II, V, and IX were mapped by bulked segregant analysis (BSA). Furthermore, six SNP markers associated with frost tolerance from candidate regions were developed and validated. Above all, a MAS system for the frost tolerance screening of early breeding offspring was established. This study highlights the practical advantages of applying diallel populations to broaden and improve frost-tolerant germplasm resources.

Recombinant human brain natriuretic peptide (rh-BNP) is commonly used as a decongestive therapy. This study aimed to investigate the instant effects of rh-BNP on cardiac output and venous return function in post-cardiotomy patients with congestive heart failure (CHF).Twenty-four post-cardiotomy heart failure patients were enrolled and received a standard loading dose of rh-BNP. Haemodynamic monitoring was performed via a pulmonary artery catheter before and after the administration of rh-BNP. The cardiac output and venous return functions were estimated by depicting Frank-Starling and Guyton curves. After rh-BNP infusion, variables reflecting cardiac congestion and venous return function, such as pulmonary artery wedge pressure, mean systemic filling pressure (Pmsf) and venous return resistance index (VRRI), reduced from 15 ± 3 to 13 ± 3 mmHg, from 32 ± 7 to 28 ± 7 mmHg and from 6.7 ± 2.6 to 5.7 ± 1.8 mmHg min mrh-BNP might ameliorate venous return rather than cardiac output function in post-cardiotomy CHF patients.

Past studies have investigated the association between the built environment and active lifestyle, but the environmental exposure in most of these studies was measured in residential settings with predefined boundaries. In this study, we investigated the relationship between destinations in cities and walking behaviors in national and provincial capital cities in China based on a nationwide smartphone dataset. We identified destinations that were strongly and consistently associated with walking behaviors based on geographic information systems (GIS) spatial analysis. Results from this study suggest that certain components, especially parks, rivers, running tracks, of the built environment were positively associated with walking behaviors. Parks were consistently associated with more frequent walking behaviors while rivers were associated with longer walking trajectories. Findings from this study help better understand to what extent urban destinations influence physical activities and support evidence-based urban planning and health promotion in cities.

In this work, we discuss the numerical method for the solution of the Black-Scholes model. First of all, the asymptotic convergence for the solution of Black-Scholes model is proved. Second, we develop a linear, unconditionally stable, and second-order time-accurate numerical scheme for this model. By using the finite difference method and Legendre-Galerkin spectral method, we construct a time and space discrete scheme. Finally, we prove that the scheme has second-order accuracy and spectral accuracy in time and space, respectively. Several numerical experiments further verify the convergence rate and effectiveness of the developed scheme.

Effect of external-recycle operations on the heat-transfer efficiency, specifically for the power-law fluid flowing in double-pass concentric circular heat exchanger under sinusoidal wall fluxes, is investigated theoretically in the developed countries. Given that the fluid is heated twice on both sides of the impermeable sheet, four flow patterns proposed in recycling double-pass operations are expected to make substantial improvements in the performance of heat exchanger device in this study. Theoretical predictions point out that the heat-transfer efficiency increases with the ratio of channel thickness of double-pass concentric circular heat exchanger for all new designs under the same working dimension and the operational condition. The fluid velocity within the double-pass heat exchanger is increased by the fluids flowing through divided subchannels, which contributed to the higher convective heat-transfer efficiency. A simplified mathematical formulation was derived for double-pass concentric circular heat exchangers and would be a significant contribution to analyze heat transfer problems with sinusoidal wall fluxes at boundaries. The results deliver the optimal performance for the proposed four configurations with the use of external recycle compared to those conducted in single-pass, where an impermeable sheet is not inserted. The influences of power-law index and impermeable-sheet position on average Nusselt numbers under various flow patterns are also delineated. The distribution of dimensionless wall temperature was lower at the level of relative smaller thickness of annular channel, and the average Nusselt numbers for four external-recycle configurations and single-pass device were more suitable for operating under same condition. The ratio of the power consumption increment to heat-transfer efficiency enhancement demonstrates the economic feasibility among various configurations of double-pass concentric circular heat exchanger. The results also show that the external-recycle configuration (say Type B in the present study) serves as an important economic advantage in designing concentric circular heat exchangers for heating power-law fluids due to the smaller volumetric flow rate in annular channel with exiting outlet temperature.

Background Disco-interaction protein 2 homologue B (DIP2B) plays an important role in DNA methylation. There have been many reports on DIP2B in various diseases, but neither the diagnostic value nor the prognostic value of DIP2B across cancer types has been deeply explored. Methods The expression levels of DIP2B in 33 cancer types were analysed based on data sets from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. The relationships of DIP2B expression with immune cell infiltration and immune-related gene expression were studied via the CIBERSORT, ESTIMATE and TISIDB tools. Gene set variation analysis (GSVA) was performed to identify pathways related to DIP2B. DIP2B knockdown by siRNA was performed in breast cancer cell lines to investigate the effect on proliferation, apoptosis and migration. The relationships of DIP2B expression with clinicopathological features and prognosis were analysed based on immunohistochemistry. Results DIP2B was highly expressed in 26 of 33 cancer types and was significantly associated with poor overall survival (OS) in breast invasive carcinoma (BRCA), mesothelioma and chromophobe renal cell carcinoma (each P P P P P = 0.023 and P = 0.069). Conclusions DIP2B may be a prognostic biomarker for BRCA, especially for the Her-2 + subtype. DIP2B is associated with a “cold” tumour immune microenvironment in BRCA and might serve as a future target for immunotherapy.

Supplementary Figure S1 from Synergistic Induction of DOC-2/DAB2 Gene Expression in Transitional Cell Carcinoma in the Presence of GATA6 and Histone Deacetylase Inhibitor

The down-regulation of DOC-2/DAB2 gene, which encodes a unique phosphoprotein modulating signal pathways elicited by exogenous stimuli, is often associated with several cancer types; however, the underlying mechanism is still unknown. Dramatically different expression levels of DOC-2/DAB2 mRNA and protein are observed among several human transitional cell carcinoma (TCC) cell lines, suggesting that transcriptional regulation may play a role in these cells. In this study, we have shown that the histone acetylation status associated with the 5′ upstream regulatory sequence of DOC-2/DAB2 gene is one of the key determinants for its gene expression. In addition, GATA6 but not other GATA family members, such as GATA2 and GATA4, can specifically induce DOC-2/DAB2 promoter activity, although GATA transcription factors share a very similar DNA-binding sequence. We also show that increased histone acetylation and the presence of GATA6 have a synergistic effect on DOC-2/DAB2 promoter activity, which results in the elevation of DOC-2/DAB2 protein expression. Thus, we conclude that transcriptional regulation of DOC-2/DAB2 gene in human TCC is determined by histone acetylation and a specific transcription factor (i.e., GATA6), which underlie the reduced DOC-2/DAB2 protein expression in TCC cells.

Supplementary Table and Figure from The Role of DOC-2/DAB2 in Modulating Androgen Receptor–Mediated Cell Growth via the Nongenomic c-Src–Mediated Pathway in Normal Prostatic Epithelium and Cancer

Prostate cancer is initially responsive to androgen ablation, but prostate cancer tumors invariably progress to an androgen-independent state that is ultimately lethal. The onset of the androgen-independent prostate cancer is often associated with up-regulation of the androgen receptor that can cause antagonists to exhibit agonistic activity, which could lead to the failure of androgen ablation therapy. We describe a unique protein—DOC-2/DAB2 (differentially expressed in ovarian cancer-2/disabled 2)—that antagonizes androgen receptor–mediated cell growth in prostate cancer cells via interaction with c-Src protein. This interaction causes inactivation of Erk and Akt proteins critical for proliferation and survival of prostate cancer cells. However, DOC-2/DAB2 does not change the capacity of androgen receptor to regulate the transcription of androgen-responsive reporter genes, indicating that DOC-2/DAB2 selectively inhibits androgen receptor–mediated cell growth in androgen-independent prostate cancer by disrupting the androgen receptor/c-Src complex. In normal prostatic epithelia, DOC-2/DAB2 protein levels are more abundant than androgen receptor protein levels and reduced endogenous DOC-2/DAB2 protein levels in these cells by DOC-2/DAB2 RNA interference result in enhancing androgen receptor–mediated cell growth. We conclude that DOC-2/DAB2 can modulate androgen receptor–mediated cell growth in both normal and malignant prostatic epithelial cells and the outcome of this study could evolve into a new therapeutic strategy of prostate cancer.

Background Sepsis is an abnormal immune response after infection, wherein the lung is the most susceptible organ to fail, leading to acute lung injury. To overcome the limitations of current therapeutic strategies and develop more specific treatment, the inflammatory process, in which T cell-derived extracellular vesicles (EVs) play a central role, should be explored deeply. Methods Liquid chromatography–tandem mass spectrometry was performed for serum EV protein profiling. The serum diacylglycerol kinase kappa (DGKK) and endotoxin contents of patients with sepsis-induced lung injury were measured. Apoptosis, oxidative stress, and inflammation in A549 cells, bronchoalveolar lavage fluid, and lung tissues of mice were measured by flow cytometry, biochemical analysis, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and western blot. Results DGKK, the key regulator of the diacylglycerol (DAG)/protein kinase C (PKC) pathway, exhibited elevated expression in serum EVs of patients with sepsis-induced lung injury and showed strong correlation with sepsis severity and disease progression. DGKK was expressed in CD4+ T cells under regulation of the NF-κB pathway and delivered by EVs to target cells, including alveolar epithelial cells. EVs produced by CD4+ T lymphocytes exerted toxic effects on A549 cells to induce apoptotic cell death, oxidative cell damage, and inflammation. In mice with sepsis induced by cecal ligation and puncture, EVs derived from CD4+ T cells also promoted tissue damage, oxidative stress, and inflammation in the lungs. These toxic effects of T cell-derived EVs were attenuated by the inhibition of PKC and NOX4, the downstream effectors of DGKK and DAG. Conclusions This approach established the mechanism that T-cell-derived EVs carrying DGKK triggered alveolar epithelial cell apoptosis, oxidative stress, inflammation, and tissue damage in sepsis-induced lung injury through the DAG/PKC/NOX4 pathway. Thus, T-cell-derived EVs and the elevated distribution of DGKK should be further investigated to develop therapeutic strategies for sepsis-induced lung injury.

We initiate the study of matroid problems in a new oracle model called dynamic oracle. Our algorithms in this model lead to new bounds for some classic problems, and a "unified" algorithm whose performance matches previous results developed in various papers. We also show a lower bound that answers some open problems from a few decades ago. Concretely, our results are as follows. * We show an algorithm with $\tilde{O}_k(n+r\sqrt{r})$ dynamic-rank-query and time complexities for the matroid union problem over $k$ matroids. This implies the following consequences. (i) An improvement over the $\tilde{O}_k(n\sqrt{r})$ bound implied by [Chakrabarty-Lee-Sidford-Singla-Wong FOCS'19] for matroid union in the traditional rank-query model. (ii) An $\tilde{O}_k(|E|+|V|\sqrt{|V|})$-time algorithm for the $k$-disjoint spanning tree problem. This improves the $\tilde{O}_k(|V|\sqrt{|E|})$ bounds of Gabow-Westermann [STOC'88] and Gabow [STOC'91]. * We show a matroid intersection algorithm with $\tilde{O}(n\sqrt{r})$ dynamic-rank-query and time complexities. This implies new bounds for some problems and bounds that match the classic ones obtained in various papers, e.g. colorful spanning tree [Gabow-Stallmann ICALP'85], graphic matroid intersection [Gabow-Xu FOCS'89], simple scheduling matroid intersection [Xu-Gabow ISAAC'94], and Hopcroft-Karp combinatorial bipartite matching. More importantly, this is done via a "unified" algorithm in the sense that an improvement over our dynamic-rank-query algorithm would imply improved bounds for all the above problems simultaneously. * We show simple super-linear ($\Omega(n\log n)$) query lower bounds for matroid intersection in our dynamic-rank-oracle and the traditional independence-query models; the latter improves the previous $\log_2(3)n - o(n)$ bound by Harvey [SODA'08] and answers an open problem raised by, e.g., Welsh [1976] and CLSSW [FOCS'19]., Comment: To appear at STOC 2023. Abstract shortened to meet arXiv requirement

Hepatocytes, the major parenchymal cells in the liver, are responsible for a variety of cellular functions including carbohydrate, lipid and protein metabolism, detoxification and immune cell activation to maintain liver homeotasis. Recent studies show hepatocytes play a pivotal role in liver inflammation. After receiving liver insults and inflammatory signals, hepatocytes may undergo organelle damage, and further respond by releasing mediators and expressing molecules that can act in the microenvironment as well as initiate a robust inflammatory response. In this review, we summarize how the hepatic organelle damage link to liver inflammation and introduce numerous hepatocyte-derived pro-inflammatory factors in response to chronic liver injury.

BackgroundMetal components of environmental PM2.5 are associated with the exacerbation of allergic diseases like asthma. In our recent hospital-based population study, exposure to vanadium is shown to pose a significant risk for current asthma, but the causal relationship and its underlying molecular mechanisms remain unclear.ObjectiveWe sought to determine whether vanadium co-exposure can aggravate house dust mite (HDM)-induced allergic airway inflammation and remodeling, as well as investigate its related mechanisms.MethodsAsthma mouse model was generated by using either vanadium pentoxide (V2O5) or HDM alone or in combination, in which the airway inflammation and remodeling was investigated. The effect of V2O5 co-exposure on HDM-induced epithelial-derived cytokine release and oxidative stress (ROS) generation was also examined by in vitro analyses. The role of ROS in V2O5 co-exposure-induced cytokine release and airway inflammation and remodeling was examined by using inhibitors or antioxidant.ResultsCompared to HDM alone, V2O5 co-exposure exacerbated HDM-induced airway inflammation with increased infiltration of inflammatory cells and elevated levels of Th1/Th2/Th17 and epithelial-derived (IL-25, TSLP) cytokines in the bronchoalveolar lavage fluids (BALFs). Intriguingly, V2O5 co-exposure also potentiated HDM-induced airway remodeling. Increased cytokine release was further supported by in vitro analysis in human bronchial epithelial cells (HBECs). Mechanistically, ROS, particularly mitochondrial-derived ROS, was significantly enhanced in HBECs after V2O5 co-exposure as compared to HDM challenge alone. Inhibition of ROS with its inhibitor N-acetyl-L-cysteine (NAC) and mitochondrial-targeted antioxidant MitoTEMPO blocked the increased epithelial release caused by V2O5 co-exposure. Furthermore, vitamin D3 as an antioxidant was found to inhibit V2O5 co-exposure-induced increased airway epithelial cytokine release and airway remodeling.ConclusionsOur findings suggest that vanadium co-exposure exacerbates epithelial ROS generation that contribute to increased allergic airway inflammation and remodeling.