Acetyl-CoA carboxylase 1 depletion suppresses de novo fatty acid synthesis and mitochondrial ß-oxidation in castration-resistant prostate cancer cells.

Cancer cells, including those of prostate cancer (PCa), often hijack intrinsic cell signaling to reprogram their metabolism. Part of this reprogramming includes the activation of de novo synthesis of fatty acids that not only serve as building blocks for membrane synthesis but also as energy sources for cell proliferation. However, how de novo fatty acid synthesis contributes to PCa progression is still poorly understood. Herein, by mining public datasets, we discovered that the expression of acetyl-CoA carboxylase alpha (ACACA), which encodes acetyl-CoA carboxylase 1 (ACC1), was highly expressed in human PCa. In addition, patients with high ACACA expression had a short disease-free survival time. We also reported that depletion of ACACA reduced de novo fatty acid synthesis and PI3K/AKT signaling in the human castration-resistant PCa (CRPC) cell lines DU145 and PC3. Furthermore, depletion of ACACA downregulates mitochondrial beta-oxidation, resulting in mitochondrial dysfunction, a reduction in ATP production, an imbalanced NADP+/NADPhydrogen(H) ratio, increased reactive oxygen species, and therefore apoptosis. Reduced exogenous fatty acids by depleting lipid or lowering serum supplementation exacerbated both shRNA depletion and pharmacological inhibition of ACACA-induced apoptosis in vitro. Collectively, our results suggest that inhibition of ectopic ACACA, together with suppression of exogenous fatty acid uptake, can be a novel strategy for treating currently incurable CRPC.

Blended BA.5 infection within 8 days after a boosted bivalent mRNA vaccination strengthens and lengthens the host immunity.

The impact of SARS-CoV-2 infection shortly after vaccination on vaccine-induced immunity is unknown, which is also one of the concerns for some vaccinees during the pandemic. Here, based on a cohort of individuals who encountered BA.5 infection within 8 days after receiving the fourth dose of a bivalent mRNA vaccine, preceded by three doses of inactivated vaccines, we show that booster mRNA vaccination provided 48% protection efficacy against symptomatic infections. At Day 7 postvaccination, the level of neutralizing antibodies (Nabs) against WT and BA.5 strains in the uninfected group trended higher than those in the symptomatic infection group. Moreover, there were greater variations in Nabs levels and a significant decrease in virus-specific CD4+ T cell response observed in the symptomatic infection group. However, symptomatic BA.5 infection significantly increased Nab levels against XBB.1.9.1 and BA.5 (symptomatic > asymptomatic > uninfected group) at Day 10 and resulted in a more gradual decrease in Nabs against BA.5 compared to the uninfected group at Day 90. Our data suggest that BA.5 infection might hinder the early generation of Nabs and the recall of the CD4+ T cell response but strengthens the Nab and virus-specific T cell response in the later phase. Our data confirmed that infection can enhance host immunity regardless of the short interval between vaccination and infection and alleviate concerns about infections shortly after vaccination, which provides valuable guidance for developing future vaccine administration strategies.

Effects of allyl isothiocyanate fumigation on medicinal plant root knot disease control, plant survival, and the soil bacterial community.

BACKGROUND: Allyl isothiocyanate (AITC) is a natural product with high volatility that is used as a biofumigant to alleviate soil-borne plant diseases, and problems such as root knot nematodes (RKNs) that necessitate continuous cropping. However, little research has assessed the effects of AITC fumigation on medicinal plants. RESULTS: AITC significantly reduced the population of RKNs in soil (p < 0.0001) and showed an excellent RKN disease control effect within 6 months after sowing Panax notoginseng (p < 0.0001). The seedling survival rate of 2-year-old P. notoginseng was approximately 1.7-fold higher after soil treatment with AITC (p = 0.1008). 16S rRNA sequencing indicated that the AITC treatment affected bacterial richness rather than diversity in consecutively cultivated (CC) soil. Furthermore, biomarkers with statistical differences between AITC-treated and untreated CC soil showed that Pirellulales (order), Pirellulaceae (family), Pseudomonadaceae (family), and Pseudomonas (genus) played important roles in the AITC-treated group. In addition, the microbiome functional phenotypes predicted using the BugBase tool suggested that AITC treatment is more conducive to improving CC soil through changes in the bacterial community structure. Crucially, our research also suggested that AITC soil treatment significantly increases soil organic matter (p = 0.0055), total nitrogen (p = 0.0054), and available potassium (p = 0.0373), which promotes the survival of a succeeding medicinal plant (Polygonatum kingianum). CONCLUSION: AITC is an ecologically friendly soil treatment that affects the top 10 bacterial richness but not diversity. It could also provide a basis for a useful agricultural soil management measure to alleviate soil sickness.

Controlling the Triplet Potential Energy Surface of Bimetallic Platinum(II) Complex by Constructing Structure-Property Relationship: A Theoretical Exploration.

For phosphorescent materials, managing the triplet potential energy surface stands for controlling the phosphorescence quantum yield. However, due to the complexity and variability, the triplet potential energy surface can be managed with difficulty. In this work, a series of bimetallic Pt(II) complexes, namely Pt-1, Pt-1-1, Pt-1-2, Pt-2, Pt-3-5, and Pt-6-7, are employed as models to construct a relationship between the structures and triplet potential energy surfaces, aiming to achieve meaningful information to manage the triplet potential energy surface. On the basis of the results, it is observed that the triplet potential energy surface has an intimate connection with the structures of bimetallic Pt(II) complexes. In the case of the primordial Pt(II) complex, the triplet potential energy surface consists of two minimal points, illustrating various properties, which can largely affect the phosphorescence quantum yield. Once the intramolecular steric hindrance, restriction effect, and metallophilic interaction (Pt-Pd/Pd-Pd) are employed by tailoring the structures of primordial Pt(II) complexes, the triplet potential energy surface can be reconstructed via one minimal point-charactered short metal-metal distance, resulting in different photophysical properties. The relationship between the triplet potential energy surface and structure is essentially unveiled from the structural and electronic viewpoints. The conclusions originated from the structural and electronic investigations can be regarded as indicators to accurately and expediently predict the triplet potential energy surfaces of bimetallic Pt(II) complexes. The results presented here are helpful in addressing the designed strategies as they show that the triplet potential energy surfaces of bimetallic Pt(II) complexes can be properly tuned.

Inhibitory mechanism of 6-Pentyl-2H-pyran-2-one secreted by Trichoderma atroviride T2 against Cylindrocarpon destructans.

Root rot caused by Cylindrocarpon destructans is one of the most devastating diseases of Panax notoginseng, and Trichoderma species are potential agents for the biocontrol of fungal diseases. Thus, we screened a total of 10 Trichoderma isolates against C. destructans and selected Trichoderma atroviride T2 as an antagonistic strain for further research. 6-Pentyl-2H-pyran-2-one (6PP) was identified as an important active metabolite in the fermentation broth of the strain and exhibited antifungal activity against C. destructans. Transcriptome and metabolome analyses showed that 6PP significantly disturbed the metabolic homeostasis of C. destructans, particularly the metabolism of amino acids. By constructing a gene coexpression network, ECHS1 was identified as the hub gene correlated with 6PP stress. 6PP significantly downregulated the expression of ECHS1 at the transcriptional level and combined with the ECHS1 protein. Autophagy occurred in C. destructans cells under 6PP stress. In conclusion, 6PP may induce autophagy in C. destructans by downregulating ECHS1 at the transcriptional level and inhibiting ECHS1 protein activity. 6PP is a potential candidate for the development of new fungicides against C. destructans.

Benzothiazole inhibits the growth of Phytophthora capsici through inducing apoptosis and suppressing stress responses and metabolic detoxification.

Benzothiazole (BZO) is an antimicrobial secondary metabolite volatilized by many plants and microbes. However, the mechanism of BZO against phytopathogens is still unclear. Here, we found that BZO has antimicrobial activity against the oomycete pathogen Phytophthora capsici. Transcriptome and proteome analyses demonstrated that BZO significantly suppressed the expression of genes and proteins involved in morphology, abiotic stress defense and detoxification, but induced the activity of apoptosis. Annexin V-FITC/PI staining confirmed that the process of apoptosis was significantly induced by BZO at concentration of 150 mg L-1. FITC-phalloidin actin-cytoskeleton staining combined with hyphal cell wall staining and hyphal ultrastructure studies further confirmed that BZO disrupted the cell membrane and hyphal morphology through disrupting the cytoskeleton, eventually inhibiting the growth of hyphae. These data demonstrated that BZO has multiple modes of action and may act as potential leading compound for the development of new oomycete fungicides. These results also showed that the combination of transcriptomic and proteomic approaches was a useful method for exploring the novel antifungal mechanisms of natural compounds.

Correction: Effects of UV-B radiation on the infectivity of Magnaporthe oryzae and rice disease-resistant physiology in Yuanyang terraces.

Correction for 'Effects of UV-B radiation on the infectivity of Magnaporthe oryzae and rice disease-resistant physiology in Yuanyang terraces' by Xiang Li et al., Photochem. Photobiol. Sci., 2018, 17, 8-17.

Effects of UV-B radiation on the infectivity of Magnaporthe oryzae and rice disease-resistant physiology in Yuanyang terraces.

The traditional rice variety "Baijiaolaojing" was planted in Yuanyang terraces (1600 m altitude) under field conditions. The effects of enhanced UV-B radiation (0 kJ m-2, 2.5 kJ m-2, 5.0 kJ m-2 and 7.5 kJ m-2) on the rice-Magnaporthe oryzae system were studied with respect to the Magnaporthe oryzae infection, the disease-resistance physiology of the rice and the rice blast disease condition. The results showed that under enhanced UV-B radiation, the infectivity of Magnaporthe oryzae was decreased, which could significantly inhibit its growth and sporulation. The activities of rice leaf disease-resistance-related enzymes (phenylalanine ammonia-lyase, lipoxygenase, chitinase and ß-1,3-glucanase) were significantly increased under enhanced UV-B radiation. Following inoculation with Magnaporthe oryzae, levels of disease-resistance-related substances in the rice leaves were significantly increased. Among the results, it was found that leaves after UV-B radiation had a more significant resistance response. The level of UV-B irradiation showed a parabolic relationship with the rice blast index (r2 = 0.85, P < 0.01; in the control group, r2 = 0.88, P < 0.01). The disease index decreased with increase in irradiation. The DI was at a minimum with enhanced UV-B irradiance of 4 kJ m-2; thereafter, it increased with increasing irradiation. The enhanced UV-B radiation had a direct impact on the growth of rice and Magnaporthe oryzae, and it indirectly changed the rice-Magnaporthe oryzae system. UV-B radiation could reduce the harmful impact of rice blast.

Proteomic analysis on zoxamide-induced sensitivity changes in Phytophthora cactorum.

Zoxamide is an important fungicide for oomycete disease management. In this study, we established the baseline sensitivity of Phytophthora cactorum to zoxamide and assessed the risk of developing resistance to zoxamide using ultraviolet irradiation and fungicide taming methods. All 73 studied isolates were sensitive to zoxamide, with effective concentrations for 50% inhibition of mycelial growth ranging from 0.04 to 0.29 mg/L and mean of 0.15 mg/L. Stable zoxamide-resistant mutants of P. cactorum were not obtained from four arbitrarily selected isolates by either treating mycelial cultures with ultraviolet irradiation or adapting mycelial cultures to the addition of increasing zoxamide concentrations. However, the sensitivity of the isolates to zoxamide could be easily reduced by successive zoxamide treatments. In addition to displaying decreased sensitivity to zoxamide, these isolates also showed decreased sensitivity to the fungicides flumorph and cymoxanil. Proteomic analysis indicated that some proteins involved in antioxidant detoxification, ATP-dependent multidrug resistance, and anti-apoptosis activity, are likely responsible for the induced decrease in the sensitivity of P. cactorum to zoxamide compared to controls. Further semi-quantitative PCR analysis demonstrated that the gene expression profiles of most of above proteins were consistent with the proteomic analysis. Based on the above results, P. cactorum shows low resistance risk to zoxamide; however, the fungicidal effect of zoxamide might be decreased due to induced resistance when this fungicide is continuously applied.

Proteomic analysis of zoxamide-induced changes in Phytophthora cactorum.

In this study, the global proteomic response of Phytophthora cactorum to zoxamide was evaluated using a two-dimensional gel electrophoresis (2-DE)-based proteomic approach. Among the 21 proteins identified by matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS), four cytoskeleton-related proteins were down-regulated upon addition of zoxamide. Five detoxification metabolism enzymes, seven sugar metabolism proteins and one mitochondria-related protein were up-regulated by more than 2-fold in response to zoxamide. Taken together, these results suggest that zoxamide can decrease the expression of cytoskeleton-related proteins of P. cactorum, resulting in cell death; however, the up-regulation of detoxification metabolism-related enzymes may protect P. cactorum against zoxamide, and the up-regulation of proteins related to sugar metabolism and mitochondria may lead to the generation of more energy for detoxification metabolism. These data also suggest that proteomics may be useful not only in exploring the mode of action of fungicides but also for gaining insight into the resistance mechanisms that pathogens employ against fungicides.

Diallyl Trisulfide Acts as a Soil Disinfestation Against the Ilyonectria destructans through Inducing the Burst of Reactive Oxygen Species.

Soil-borne diseases represent an impediment to the sustainable development of agriculture. A soil-borne disease caused by Ilyonectria destructans severely impacts Panax species, and soil disinfestation has proven to be an effective management approach. Here, diallyl trisulfide (DATS), derived from garlic, exhibited pronounced inhibitory effects on the growth of I. destructans in vitro tests and contributed to the alleviation of soil-borne diseases in the field. A comprehensive analysis demonstrated that DATS inhibits the growth of I. destructans by activating detoxifying enzymes, such as GSTs, disrupting the equilibrium of redox reactions. A series of antioxidant amino acids were suppressed by DATS. Particularly noteworthy is the substantial depletion of glutathione by DATS, resulting in the accumulation of ROS, ultimately culminating in the inhibition of I. destructans growth. Briefly, DATS could effectively suppress soil-borne diseases by inhibiting pathogen growth through the activation of ROS, and it holds promise as a potential environmentally friendly soil disinfestation.

Initial COVID-19 severity influenced by SARS-CoV-2-specific T cells imprints T-cell memory and inversely affects reinfection.

The immunoprotective components control COVID-19 disease severity, as well as long-term adaptive immunity maintenance and subsequent reinfection risk discrepancies across initial COVID-19 severity, remain unclarified. Here, we longitudinally analyzed SARS-CoV-2-specific immune effectors during the acute infection and convalescent phases of 165 patients with COVID-19 categorized by severity. We found that early and robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses ameliorate disease progression and shortened hospital stay, while delayed and attenuated virus-specific CD8+ T cell responses are prominent severe COVID-19 features. Delayed antiviral antibody generation rather than titer level associates with severe outcomes. Conversely, initial COVID-19 severity imprints the long-term maintenance of SARS-CoV-2-specific adaptive immunity, demonstrating that severe convalescents exhibited more sustained virus-specific antibodies and memory T cell responses compared to mild/moderate counterparts. Moreover, initial COVID-19 severity inversely correlates with SARS-CoV-2 reinfection risk. Overall, our study unravels the complicated interaction between temporal characteristics of virus-specific T cell responses and COVID-19 severity to guide future SARS-CoV-2 wave management.

Prediction of drug sensitivity based on multi-omics data using deep learning and similarity network fusion approaches.

With the rapid development of multi-omics technologies and accumulation of large-scale bio-datasets, many studies have conducted a more comprehensive understanding of human diseases and drug sensitivity from multiple biomolecules, such as DNA, RNA, proteins and metabolites. Using single omics data is difficult to systematically and comprehensively analyze the complex disease pathology and drug pharmacology. The molecularly targeted therapy-based approaches face some challenges, such as insufficient target gene labeling ability, and no clear targets for non-specific chemotherapeutic drugs. Consequently, the integrated analysis of multi-omics data has become a new direction for scientists to explore the mechanism of disease and drug. However, the available drug sensitivity prediction models based on multi-omics data still have problems such as overfitting, lack of interpretability, difficulties in integrating heterogeneous data, and the prediction accuracy needs to be improved. In this paper, we proposed a novel drug sensitivity prediction (NDSP) model based on deep learning and similarity network fusion approaches, which extracts drug targets using an improved sparse principal component analysis (SPCA) method for each omics data, and construct sample similarity networks based on the sparse feature matrices. Furthermore, the fused similarity networks are put into a deep neural network for training, which greatly reduces the data dimensionality and weakens the risk of overfitting problem. We use three omics of data, RNA sequence, copy number aberration and methylation, and select 35 drugs from Genomics of Drug Sensitivity in Cancer (GDSC) for experiments, including Food and Drug Administration (FDA)-approved targeted drugs, FDA-unapproved targeted drugs and non-specific therapies. Compared with some current deep learning methods, our proposed method can extract highly interpretable biological features to achieve highly accurate sensitivity prediction of targeted and non-specific cancer drugs, which is beneficial for the development of precision oncology beyond targeted therapy.

PlantNLRatlas: a comprehensive dataset of full- and partial-length NLR resistance genes across 100 chromosome-level plant genomes.

Plants have evolved two layers of protection against biotic stress: PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI). The primary mechanism of ETI involves nucleotide-binding leucine-rich repeat immune receptors (NLRs). Although NLR genes have been studied in several plant species, a comprehensive database of NLRs across a diverse array of species is still lacking. Here, we present a thorough analysis of NLR genes across 100 high-quality plant genomes (PlantNLRatlas). The PlantNLRatlas includes a total of 68,452 NLRs, of which 3,689 are full-length and 64,763 are partial-length NLRs. The majority of NLR groups were phyletically clustered. In addition, the domain sequences were found to be highly conserved within each NLR group. Our PlantNLRatlas dataset is complementary to RefPlantNLR, a collection of NLR genes which have been experimentally confirmed. The PlantNLRatlas should prove helpful for comparative investigations of NLRs across a range of plant groups, including understudied taxa. Finally, the PlantNLRatlas resource is intended to help the field move past a monolithic understanding of NLR structure and function.

Exogenous leucine alleviates heat stress and improves saponin synthesis in Panax notoginseng by improving antioxidant capacity and maintaining metabolic homeostasis.

Panax notoginseng saponins (PNSs) are used as industrial raw materials to produce many drugs to treat cardio-cerebrovascular diseases. However, it is a heat-sensitive plant, and its large-scale artificial cultivation is impeded by high temperature stress, leading to decreases in productivity and PNSs yield. Here, we examined exogenous foliar leucine to alleviate heat stress and explored the underlying mechanism using metabolomics. The results indicated that 3 and 5 mM exogenous foliar leucine significantly alleviated heat stress in one-year- and two-year-old P. notoginseng in pots and field trials. Exogenous foliar leucine enhanced the antioxidant capacity by increasing the activities of antioxidant enzymes (POD, SOD) and the contents of antioxidant metabolites (amino acids). Moreover, exogenous foliar leucine enhanced carbohydrate metabolism, including sugars (sucrose, maltose) and TCA cycle metabolites (citric acid, aconitic acid, succinic acid and fumaric acid), in P. notoginseng leaves, stems, and fibrous roots to improve the energy supply of plants and further alleviate heat stress. Field experiments further verified that exogenous foliar leucine increased the productivity and PNSs accumulation in P. notoginseng. These results suggest that leucine application is beneficial for improving the growth and quality of P. notoginseng under heat stress. It is therefore possible to develop plant growth regulators based on leucine to improve the heat resistance of P. notoginseng and other crops.

Virus infection pattern imprinted and diversified the differentiation of T-cell memory in transcription and function.

Introduction: Memory T (Tm) cells are a subpopulation of immune cells with great heterogeneity. Part of this diversity came from T cells that were primed with different viruses. Understanding the differences among different viral-specific Tms will help develop new therapeutic strategies for viral infections. Methods: In this study, we compared the transcriptome of Tm cells that primed with CMV, EBV and SARS-CoV-2 with single-cell sequencing and studied the similarities and differences in terms of subpopulation composition, activation, metabolism and transcriptional regulation. Results: We found that CMV is marked by plentiful cytotoxic Temra cells, while EBV is more abundant in functional Tem cells. More importantly, we found that CD28 and CTLA4 can be used as continuous indicators to interrogate the antiviral ability of T cells. Furthermore, we proposed that REL is a main regulatory factor for CMV-specific T cells producing cytokines and plays an antiviral role. Discussion: Our data gives deep insight into molecular characteristics of Tm subsets from different viral infection, which is important to understand T cell immunization. Furthermore, our results provide basic background knowledges for T cell based vaccine development in future.

2,3-Butanediol from the leachates of pine needles induces the resistance of Panax notoginseng to the leaf pathogen Alternaria panax.

Compared with the use of monocultures in the field, cultivation of medicinal herbs in forests is an effective strategy to alleviate disease. Chemical interactions between herbs and trees play an important role in disease suppression in forests. We evaluated the ability of leachates from needles of Pinus armandii to induce resistance in Panax notoginseng leaves, identified the components via gas chromatography-mass spectrometry (GC-MS), and then deciphered the mechanism of 2,3-Butanediol as the main component in the leachates responsible for resistance induction via RNA sequencing (RNA-seq). Prespraying leachates and 2,3-Butanediol onto leaves could induce the resistance of P. notoginseng to Alternaria panax. The RNA-seq results showed that prespraying 2,3-Butanediol onto leaves with or without A. panax infection upregulated the expression of large number of genes, many of which are involved in transcription factor activity and the mitogen-activated protein kinase (MAPK) signaling pathway. Specifically, 2,3-Butanediol spraying resulted in jasmonic acid (JA) -mediated induced systemic resistance (ISR) by activating MYC2 and ERF1. Moreover, 2,3-Butanediol induced systemic acquired resistance (SAR) by upregulating pattern-triggered immunity (PTI)- and effector-triggered immunity (ETI)-related genes and activated camalexin biosynthesis through activation of WRKY33. Overall, 2,3-Butanediol from the leachates of pine needles could activate the resistance of P. notoginseng to leaf disease infection through ISR, SAR and camalexin biosynthesis. Thus, 2,3-Butanediol is worth developing as a chemical inducer for agricultural production.

Genetic screening of MMP1 as a potential pathogenic gene in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous syndrome. Airway inflammation and remodeling are the two key processes involved in COPD pathogenesis. However, the key pathogenic genes driving COPD development have not been revealed. This study aims to identify and validate hub gene(s) underlying COPD development through bioinformatics analysis and experimental validation. METHODS: Three lung tissue sequencing datasets of the COPD (including GSE38974, GSE103174, and GSE106986) were analyzed. Further, differentially expressed genes (DEGs) were used to compare patients with COPD with non-COPD individuals, and the Robust Rank Aggregation (RRA) analysis was also performed. Results revealed a series of potential pathogenic genes of COPD. DEGs were subjected to KEGG, GO, and GSEA analyses. The scRNA dataset of human lung tissues (Human Lung Cell Atlas), and human primary airway epithelial cells (GSE134147) were used to identify the cell subtype localization. The qRT-PCR assay was performed in the human lung tissues, COPD mice model, and primary bronchial epithelial cells at the air-liquid interface (ALI) under cigarette smoke extract (CSE) stimulation to verify the expression of the hub genes. LASSO and GLM analysis with the hub genes were performed to identify the most critical gene. RNA-seq was performed after knocking down the critical gene using siRNA in HBECs at ALI. The potential role of the critical gene was confirmed through qRT-PCR, Western blot, and Immunofluorescence (IF) assays. RESULTS: A total of 98 genes were significantly and differently expressed in 3 GEO datasets. The KEGG and GO analyses showed that most of these genes are responsible for inflammation, immunity, and cell proliferation. The core gene set including 15 genes was screened out and consequently, the MMP1 was the most likely responsible for the progression of COPD. Moreover, we confirmed that MMP1 is significantly related to inflammatory effects and cilia function in human bronchial epithelial cells cultured at the air-liquid interface (ALI). CONCLUSION: In summary, we confirmed that inflammation and cell proliferation are potentially critical processes in COPD occurrence and development. A total of 15 potential hub genes were identified among which MMP1 was the most likely gene responsible for the development of COPD. Therefore, MMP1 is a potential molecular target of COPD therapy.

Smad3-mediated lncRNA HSALR1 enhances the non-classic signalling pathway of TGF-ß1 in human bronchial fibroblasts by binding to HSP90AB1.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the diseases with high mortality and morbidity with complex pathogenesis. Airway remodeling is an unavoidable pathological characteristic. However, the molecular mechanisms of airway remodeling are incompletely defined. METHODS: lncRNAs highly correlated with transforming growth factor beta 1(TGF-ß1) expression were chosen, the lncRNA ENST00000440406 (named HSP90AB1 Assoicated LncRNA 1, HSALR1) was chosen for further functional experiments. Dual luciferase and ChIP assay were used to detect the upstream of HSALR1, transcriptome sequencing, Cck-8, Edu, cell proliferation, cell cycle assay, and WB detection of pathway levels confirmed the effect of HSALR1 on fibroblast proliferation and phosphorylation levels of related pathways. Mice was infected with adeno-associated virus (AAV) to express HSALR1 by intratracheal instillation under anesthesia and was exposure to cigarette smoke, then mouse lung function was performed and the pathological sections of lung tissues were analyzed. RESULTS: Herein, lncRNA HSALR1 was identified as highly correlated with the TGF-ß1 and mainly expressed in human lung fibroblasts. HSALR1 was induced by Smad3 and promoted fibroblasts proliferation. Mechanistically, it could directly bind to HSP90AB1 protein, and acted as a scaffold to stabilize the binding between Akt and HSP90AB1 to promote Akt phosphorylation. In vivo, mice expressed HSALR1 by AAV was exposure to cigarette smoke (CS) for COPD modeling. We found that lung function was worse and airway remodeling was more pronounced in HSLAR1 mice compare to wild type (WT) mice. CONCLUSION: Our results suggest that lncRNA HSALR1 binds to HSP90AB1 and Akt complex component, and enhances activity of the TGF-ß1 smad3-independent pathway. This finding described here suggest that lncRNA can participate in COPD development, and HSLAR1 is a promising molecular target of COPD therapy.