AIMS:To investigate the association between baseline metformin use and incident hearing loss among participants with diabetes in the UK Biobank. MATERIALS AND METHODS:This study included participants from the UK Biobank who had been diagnosed with diabetes before baseline and had no evidence of hearing loss (N = 24 981). Metformin use was determined based on self-reported medication use at the baseline assessment. Incident hearing loss was ascertained using a composite definition based on speech-reception-threshold estimate, hearing aid use, cochlear implantation and relevant ICD-10 diagnoses during follow-up. Cox proportional hazards models were used, with analyses stratified by sex and adjusted for demographic, lifestyle, socioeconomic, clinical factors, noise exposure, use of antidiabetic medications and renal function. RESULTS:During approximately 12 years of follow-up, 725 and 385 incident hearing loss events were observed among male and female participants, respectively. Sex-stratified analyses showed that, among men with diabetes, baseline metformin use was associated with a lower risk of incident hearing loss (fully adjusted model: hazard ratio [95% confidence interval], 0.846 [0.725-0.987], p = 0.0339), and this association remained generally stable across multiple sensitivity analyses. In contrast, among women with diabetes, no statistically significant association was observed between metformin use and the risk of incident hearing loss (fully adjusted model: hazard ratio [95% confidence interval], 0.977 [0.790-1.208], p = 0.8290). Further interaction analysis showed that the interaction term between metformin use and sex was not statistically significant (p for interaction = 0.260). CONCLUSIONS:In participants with diabetes from the UK Biobank, baseline metformin use was associated with a lower risk of incident hearing loss among men, whereas no significant association was observed among women. However, the interaction term between metformin use and sex was not statistically significant; therefore, it cannot yet be concluded that this association differed by sex.

Myocardial cell injury resulting from myocardial ischemia and reperfusion is one of the primary drivers behind the onset and progression of heart disease. Penehyclidine hydrochloride (PHC), a novel selective anti-cholinergic agent, exerts a protective effect against myocardial ischemia-reperfusion injury (MIRI). Rab32 belongs to the family of small GTPase proteins. The present study aimed to investigate whether PHC improved MIRI by regulating Rab32 and to explore the underlying mechanisms. Oxygen-glucose deprivation/reoxygenation (OGD/R) and left anterior descending coronary artery ligation were used to establish MIRI models in vitro and in vivo. Here, we showed that PHC upregulated the expression of Rab32 in OGD/R treated HL-1 cells. PHC alleviated OGD/R-induced cell apoptosis and intracellular and mitochondrial ROS levels, while the downregulation of Rab32 exacerbated cell injury. Rab32 was upregulated in MIRI mice and downregulated in OGD/R-induced HL-1 cells. Rab32 overexpression improved cardiac function, reduced the myocardial infarct size, and inhibited cell apoptosis and mitochondrial dysfunction, either in MIRI mice or OGD/R-induced HL-1 cells. On the mechanism, Rab32 interacted with Fancd2 in HL-1 cells. Rab32 downregulation decreased Fancd2 protein expression in mitochondria. Rab32 anchored Fancd2 to mitochondria in OGD/R treated HL-1 cells. Fancd2 knockdown reversed the protective effect of Rab32 on OGD/R-induced HL-1 cells and aggravated cardiomyocyte injury. Finally, the protective role of PHC on MIRI-caused cardiomyocyte injury was confirmed in MIRI mice. Overall, we demonstrated that Rab32 protects mitochondrial function by anchoring Fancd2 and mediates the protective effect of PHC against MIRI.

Many models have been developed for landslide displacement prediction, but owing to complex landslide-formation mechanisms and landslide-inducing factors, such models have different prediction accuracies. Thus, landslide displacement prediction remains a popular but difficult topic of research. In this paper, a landslide prediction model is proposed by combining extreme learning machine (ELM) and random search support vector regression (RS-SVR) sub-models. Particularly, the combined model decomposed accumulative landslide displacement into two terms, trend and periodic displacements, using a time series model, and simulated and predicted the two terms using the ELM and RS-SVR sub-models, respectively. The predicted trend and periodic terms are then summed to obtain the total displacement. The ELM and RS-SVR sub-models are applied to predict the deformation of Baishuihe landslide in the Three Gorges Reservoir Area (TGRA) as an example. The results showed that the model effectively improved the accuracy, stability, and scope of application of landslide displacement prediction, thus providing a new method for landslide displacement prediction.

Abstract Background Patients with prior illness are more vulnerable to heat stroke-induced injury, but the underlying mechanism is unknown. Recent studies suggested that NLRP3 inflammasome played an important role in the pathophysiology of heat stroke. Methods In this study, we used a classic animal heat stroke model. Prior infection was mimicked by using lipopolysaccharide (LPS) or lipoteichoic acid (LTA) injection before heat stroke (LPS/LTA 1 mg/kg). Mice survival analysis curve and core temperature (TC) elevation curve were produced. NLRP3 inflammasome activation was measured by using real-time PCR and Western blot. Mice hypothalamus was dissected and neuroinflammation level was measured. To further demonstrate the role of NLRP3 inflammasome, Nlrp3 knockout mice were used. In addition, IL-1β neutralizing antibody was injected to test potential therapeutic effect on heat stroke. Results Prior infection simulated by LPS/LTA injection resulted in latent inflammation status presented by high levels of cytokines in peripheral serum. However, LPS/LTA failed to cause any change in animal survival rate or body temperature. In the absence of LPS/LTA, heat treatment induced heat stroke and animal death without significant systemic or neuroinflammation. Despite a decreased level of IL-1β in hypothalamus, Nlrp3 knockout mice demonstrated no survival advantage under mere heat exposure. In animals with prior infection, their heat tolerance was severely impaired and NLRP3 inflammasome induced neuroinflammation was detected. The use of Nlrp3 knockout mice enhanced heat tolerance and alleviated heat stroke-induced death by reducing mice hypothalamus IL-1β production with prior infection condition. Furthermore, IL-1β neutralizing antibody injection significantly extended endotoxemic mice survival under heat stroke. Conclusions Based on the above results, NLRP3/IL-1β induced neuroinflammation might be an important mechanistic factor in heat stroke pathology, especially with prior infection. IL-1β may serve as a biomarker for heat stroke severity and potential therapeutic method.

The q-rung orthopair fuzzy set is a powerful and useful tool to deal with uncertainty, but in actual decision-making process, decision-makers are usually required to analyze the actual problem dynamically. Therefore in this paper, we consider the time-series q-rung orthopair fuzzy decision making. First, we introduce the new cosine similarity measure of q-ROFS which combines the cosine similarity measure and the Euclidean distance measure. Then, we combine the advantages of projection method and grey correlation degree, establishing the nonlinear programming model to calculate the weights of attributes. Furthermore, we use the exponential decay model to get the weights formulas of q-ROFS at different times. Then we replace the distance function with grey relational projection and extend TOPSIS method. Based on these, we propose a new MAGDM approach to deal with time-series q-rung orthopair fuzzy problem not only from the point of view of geometry but also from the point of view of algebra. Finally, we give a practical example to illustrate effectiveness and feasibility of the new method.

Head and neck squamous cell carcinoma (HNSCC) rank seventh among the most common type of malignant tumor worldwide. Various evidences suggest that transcriptional factors (TFs) play a critical role in modulating cancer progression. However, the prognostic value of TFs in HNSCC remains unclear. Here, we identified a risk model based on a 12-TF signature to predict recurrence-free survival (RFS) in patients with HNSCC. We further analyzed the ability of the 12-TF to predict the disease-free survival time and overall survival time in HNSCC, and found that only NR5A2 down-regulation was strongly associated with shortened overall survival and disease-free survival time in HNSCC. Moreover, we systemically studied the role of NR5A2 in HNSCC and found that NR5A2 regulated HNSCC cell growth in a TP53 status-dependent manner. In p53 proficient cells, NR5A2 knockdown increased the expression of TP53 and activated the p53 pathway to enhance cancer cells proliferation. In contrast, NR5A2 silencing suppressed the growth of HNSCC cells with p53 loss/deletion by inhibiting the glycolysis process. Therefore, our results suggested that NR5A2 may serve as a promising therapeutic target in HNSCC harboring loss-of-function TP53 mutations.

Vibrio alginolyticus, a Gram-negative halophilic zoonotic pathogen, can cause bacterial hemorrhagic septicemia in various aquaculture species and wound infections in humans. V. alginolyticus brings about huge economic losses in aquaculture all around the world. Hfq, a ubiquitous RNA-binding protein, is a global post-transcriptional regulator in most bacteria and some archaea, by facilitating base-pairing between sRNAs and their mRNA targets, and is essential for adaptation to different environments and growth conditions. Despite its important roles in the stress adaptation, virulence, nutrient utilization, and colony morphology in V. alginolyticus, further research is required to shed light on the pathways modulated by Hfq. In this study, we used metabolomics and lipidomics analytical approaches based on ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) to understand the impact of Hfq on the metabolic profile of V. alginolyticus. The deletion of the hfq gene resulted in the growth deficiency and cell elongation of V. alginolyticus cultured in the rich medium. Substantial metabolic alterations, mainly involved in amino acids, nucleotides, fatty acids, and lipids, were observed in the hfq deletion mutant strain (Δhfq) when compared to the wild-type (WT) strain and its complemented strain (hfq+). Notably, the hfq deletion induced accumulations of free fatty acids (FFAs) and nucleotides, but decreased levels of most amino acids (e.g., branched amino acids, aromatic amino acids, and aspartate family amino acids). Meanwhile, the majority of lipids (e.g., lysophosphatidylglycerol, lysophosphatidylethanolamine, phosphatidylcholine, phosphatidic acid, cardiolipin, sphingomyelin, some phosphatidylglycerol and phosphatidylethanolamine with mono- or poly-unsaturated fatty acids) were decreased, while ceramide, diacylglycerol, triacylglycerol and some phosphatidylglycerol and phosphatidylethanolamine with saturated fatty acids increased in the Δhfq strain. These data demonstrated that the hfq deletion triggered de novo synthesis of FFAs and nucleosides and enhanced the catabolism of phospholipid and sphingomyelin to further regulate cell division and growth. Additionally, the hfq deletion could inhibit the synthesis of the branched amino acids, aromatic amino acids and enhance the TCA cycle to influence cell stress defenses and energy metabolism. Our research indicates that Hfq can regulate pathways associated with cell division, growth and stress resistance, being an important metabolic modulator in V. alginolyticus.

The ancient Zhenggang landslide (47.5 million m3) represents a potential threat to the construction and safe operation of the proposed Gushui Hydropower Project and to the people living downstream. The landslide was caused by continuous rainfall from October 20 to November 5, 2008, indicating that groundwater aggravated sliding and deformation, and it can be divided into two distinct zones: zone I and zone II. Investigations of the Zhenggang landslide deposits have been conducted for 10 years, but the evolution of the landslide deformation is yet to be revealed. Geological surveys and stability analysis have revealed that the Zhenggang landslide is currently relatively stable and is not sliding. The deformational data for the deep soil layers show that subslide zone I is a translational slide, while subslide zone II is an uplift slide, and zone II is slightly more stable than zone I. Obvious interior deformational failure occurred and was observed in the exploratory adits. The numerical results show that rainfall infiltration is the main factor to induce the revival of ancient landslide, and it is necessary to strengthen the landslide risk assessment and reliability of Zhenggang landslide under the condition of rainfall infiltration. Finally, in order to reduce landslide risks, the local residents living near the landslide mass should be relocated, and measures should be taken to increase slope stability.

Heavy rainfall and changes in the water levels of reservoirs directly affect the degree of landslide disasters in major hydropower project reservoir areas. Correlation analyses of rainfall- and water-level fluctuations with landslide displacement changes can provide a scientific basis for the prevention and early warning of landslide disasters in reservoir areas. Because of the shortcomings of the traditional correlation analysis based on linear assumptions, this study proposed the use of a pseudo-maximum-likelihood-estimation-mixed-Copula (MLE-M-Copula) method instead of linear assumptions. We used the Bazimen landslide in the Three Gorges Reservoir Area as a case study to carry out the correlation analysis of the rainfall, water-level fluctuations, and landslide displacement. First, we selected several appropriate influencing factors to construct four candidate Copula models and estimated the parameters using the pseudo-MLE method. After the goodness-of-fit test, we selected the M-Copula model as the optimal model and used this model to study correlations between the monthly displacement increment of the landslide and influencing factors. We then established the joint distribution functions of these correlations. We computed and analyzed the overall and tail correlations between the displacement increment and the influencing factors, and we constructed the conditional probability distribution of the monthly displacement increment for different given conditions. The results showed that the pseudo-MLE-M-Copula method effectively quantified the correlation between the rainfall, reservoir-level fluctuations, and landslide displacement changes, and we obtained the return periods and value at risk of the influencing factors of the Bazimen landslide under different rainfall conditions and reservoir-level changes. Furthermore, the tail correlations between the monthly displacement increment of the landslide and the rainfall- and reservoir-level changes were higher than the overall correlations.

Objective: The tumour microenvironment is one of the significant factors driving the carcinogenesis of Pancreatic adenocarcinoma (PAAD). However, the underlying mechanism of how the tumour microenvironment impacts the prognosis of PAAD is not completely clear. Results: The transcriptome and clinical data of 182 PAAD program cases were downloaded from the TCGA database. Three hundred thirty-three differentially expressed genes (DEGs) between high and low stromal groups and 314 DEGs between high and low immune score groups were identified using ESTIMATE score. Based on the 203 genes differentially expressed simultaneously in two score-related comparisons, we established an 8-mRNA signature to evaluate the prognosis of PAAD patients. Kaplan-Meier curves showed significantly worse survival for patients with high-risk scores in both the training and validation groups. The risk score was an independent prognostic factor and had a high predictive value for the prognosis of patients with PAAD. By searching the TCGA database, we showed that CA9, CXCL9, and GIMAP7 from the 8-mRNA signature were associated with the infiltration levels of immunocytes by regulating FOXO1 expression in PAAD. Conclusions: Unlike traditional methods of screening for differential genes in cancer and healthy tissues, we constructed a novel 8-mRNA signature to predict the prognosis of PAAD patients by applying ESTIMATE scoring to RNA-seq-based transcriptome data. Most importantly, we identified CA9, CXCL9, and GIMAP7 from the above eight genes as regulators of immunocyte infiltration by adjusting the expression of FOXO1 in PAAD. Thus, CA9, CXCL9, and GIMAP7 might be the ideal targets of immune therapy of PAAD. Methods: ESTIMATE scoring was used to determine the stromal and immune scores of transcriptome datasets downloaded from the TCGA database. An mRNA-based prognostic signature was built for the training cohort via the LASSO Cox regression model. The signature was verified using a validation cohort. Kaplan-Meier curves and log-rank analysis were used to identify survival differences. Western blot analysis and RT-qPCR analysis were carried out to analyze the expression of specific proteins and mRNAs. IHC was performed to assess the protein levels of Forkhead box-O 1 (FOXO1), Carbonic anhydrase 9 (CA9), C-X-C motif chemokine ligand 9 (CXCL9), and GTPase, IMAP family member 7 (GIMAP7) in the tissue microarray of PAAD.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly solid tumors in the world. Aerobic glycolysis is among the characteristic features of pancreatic cancer. However, the regulatory process of aerobic glycolysis in pancreatic cancer is too complicated, and the underlying mechanism remains unexplained. Reportedly, CDK4/6 inhibitors repress breast cancer cell proliferation by modulating glucose metabolism. Here, we reveal that the CDK4/6 inhibitor, PD0332991 stabilized FBP1 to hinder aerobic glycolysis in pancreatic cancer. We also show that the CDK4/6-E2?F1 signaling pathway mediated an increase in MAGED1 expression, promoting FBP1 degradation in pancreatic cancer. We, therefore, might have identified a novel mechanism by which the CDK4/6 inhibitor, PD0332991 blocks the Warburg effect of pancreatic cancer by stabilizing FBP1.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumour that is characteristically unresponsive to most chemotherapeutic regimens. Bromodomain and extra terminal domain (BET) inhibitors that specifically repress the function of BET family proteins, such as BRD4, are under evaluation in clinical trials for their activity in repressing cancer growth. However, resistance to BET inhibitors has hindered their further clinical application in pancreatic cancer. We previously reported that FBP1 contributes to the resistance to BET inhibitors, but the underlying mechanism of this resistance remains unclear. Herein, we demonstrate that FBP1 is a binding partner of BRD4 in pancreatic cancer cells. We reveal that FBP1 binds to the BD2 domain of BD4 in an acetylation-dependent manner. Moreover, we found that Tip60 and HDAC3 were key to the acetylation and de-acetylation of FBP1 at K110 and K113, which are critical for mediating FBP1-BRD4 binding in pancreatic cancer cells. Furthermore, our data indicate that FBP1 decreases the expression of genes downstream of BRD4 to inhibit pancreatic cancer cell progression. Our results, therefore, provide evidence of the novel anti-tumour effect of FBP1 via its blockade of BRD4 function in pancreatic cancer cells.

This study aimed to develop a novel surgery classification for an endoscopic approach to middle ear cholesteatoma. We retrospectively analyzed the surgical approaches and outcomes of patients with middle ear cholesteatoma. Middle ear cholesteatoma surgeries were divided into four types and two special types as follows: type I, attic retraction pocket, which only requires tympanostomy tube placement or retraction pocket resection and cartilage reconstruction; type II, cholesteatoma which is limited to the attic or in which endoscopy can confirm complete removal of mastoid cholesteatoma lesions, including type II a, requiring only use of a curette, and type II b, requiring use of an electric drill or chisel; type III, cholesteatoma not limited to the attic, in which endoscopy cannot confirm complete removal of mastoid cholesteatoma lesions, requiring the combined use of endoscope and microscope to perform endoscopic tympanoplasty and "Canal Wall Up" mastoidectomy; type IV, extensive involvement of mastoid cavity cholesteatoma lesions and/or cases with a potential risk of complications, removal of which can only be performed under a microscope for "Canal Wall Down" mastoidectomy. In addition, there were two special types: "difficult external auditory canal" and congenital cholesteatoma in children. In our system, type I and type II middle ear cholesteatoma surgery was completely performed under an endoscope alone. However, estimating the extent of the lesions, determining the choice of mastoid opening and reestablishing ventilation are the key points for an endoscopic approach to middle ear cholesteatoma. The classification of endoscopic middle ear cholesteatoma surgery may benefit the selection of surgical indications.

The project delivery mode is an extremely important link in the life cycle of water engineering. Many cases show that increases in the costs, construction period, and claims in the course of the implementation of water engineering are related to the decision of the project delivery mode in the early stages. Therefore, it is particularly important to choose a delivery mode that matches the water engineering. On the basis of identifying the key factors that affect the decision on the project delivery system and establishing a set of index systems, a comprehensive decision of engineering transaction is essentially considered to be a fuzzy multi-attribute group decision. In this study, intuitionistic fuzzy entropy was used to determine the weight of the influencing factors on the engineering transaction mode; then, intuitionistic fuzzy entropy was used to determine the weight of decision experts. Thus, a comprehensive scheme-ranking model based on an intuitionistic fuzzy hybrid average (IFHA) operator and intuitionistic fuzzy weighted average (IFWA) operator was established. Finally, a practical case analysis of a hydropower station further demonstrated the feasibility, objectivity, and scientific nature of the decision model.

Background and aims The evidence concerning the association between hearing loss and stroke is limited. We aimed to investigate the association of hearing loss with risk of stroke and its subtypes among the middle-aged and older Chinese population. Methods We included 19,238 participants aged 64.6 years from the Dongfeng-Tongji Cohort in 2013. Hearing loss was classified into normal, mild, moderate, severe or greater levels by the pure tone average at speech frequency and high frequency, respectively. We calculated the odds ratios of hearing loss and stroke by logistic regression models. Results With the increase of hearing loss level, the prevalence risk of stroke has gradually increased. Compared with normal hearing, participants having severe or greater hearing loss had a higher stroke risk of 76% and 39% at speech frequency and at high frequency, respectively. Similarly, individuals with severe or greater hearing loss had an increased risk of ischemic stroke of 69% and 52% at speech frequency and high frequency, respectively; while severe or greater hearing loss was associated with about a 2-fold risk of hemorrhagic stroke than normal hearing only at speech frequency. Stratified analysis suggested that some high cardiovascular risk participants such as male, age ≥65, exposed to occupational noise, smoker and with diabetes, hypertension or hyperlipidemia had higher risk of stroke. Furthermore, severe or greater hearing loss combined with age, diabetes, hypertension and hyperlipidemia had joint effects on stroke. Conclusions The results have suggested a dose-response relationship between hearing loss and stroke risk in middle-aged and older adults.

The present study was designed to investigate the effect of hypoxia inducible factor-1α (HIF-1α) on diabetic nephropathy (DN) with hypertension. HIF-1α deficient mice (Mx/HIF-1α-/-) were constructed and treated with streptozotocin (STZ) injection for hypertensive DN induction. Normal C57BL/6 mice received STZ or no treatment (normal) were considered as controls. Three days post STZ administration; body weight, fasting blood glucose (FBG), 24 h urinary albumin and systolic blood pressure (SBP) were measured weekly. Periodic acid-Schiff's staining was performed for histologic analysis of glomeruli damage. In comparison with the normal control, significant upregulation and downregulation of HIF-1α was, respectively, detected in diabetic and HIF-1α-/- mice (P<0.01). In comparison with STZ-induced diabetic mice, HIF-1α-/- + STZ mice displayed reduced body weight, and increased FBG, urinary albumin and SBP. PAS showed HIF-1α-/- + STZ mice had damaged kidney tissues, with more renal fibrosis and apparent glomerular hypertrophy. These results demonstrated that HIF-1α deficiency accelerated DN progression with increasing hypertension in mice.

Background and aims: The association between hearing loss and coronary heart disease (CHD) is inconsistent. We aimed to investigate the association of hearing loss with prevalent CHD and CHD-related biomarkers among a middle aged and elderly Chinese population. Methods: We included 14,755 Chinese aged 64.6 years from the Dongfeng-Tongji Cohort in 2013. Hearing loss was classified into normal, mild, moderate or greater levels by the pure tone average (PTA) at low frequency and high frequency, respectively. Logistic regression models were used to estimate the odds ratios (ORs) of CHD risk in relation to hearing loss. Linear regression models were used to evaluate the effect of hearing loss on CHD-related biomarkers. Results: The adjusted ORs for prevalent CHD increased gradually with the increasing hearing loss levels. Compared with normal hearing, individuals having mild-and moderate or greater-hearing loss had a higher CHD risk of 19% and 20% at low frequency, and 33% and 41% at high frequency, respectively (all p for trend < 0.05). The associations were more evident among subjects who were females, overweight, exposed to occupational noise and with hyperglycemia, hypertension or dyslipidemia at low frequency, and those with hyperglycemia at high frequency. Meanwhile, moderate or greater hearing loss combined with overweight, hyperglycemia, hypertension or dyslipidemia had joint effects on CHD. In addition, the majority of CHD-related biomarkers worsened with increasing hearing loss levels. Conclusions: There may be a dose-response relationship between hearing loss and CHD prevalence, and the association could partially be explained by intermediate CHD-related biomarkers. (C) 2018 Elsevier B.V. All rights reserved.

Combined effect of cigarette smoking and occupational noise exposure on hearing loss has rarely been evaluated among Chinese population, especially among females. This cross-sectional study was conducted in 11196 participants of Dongfeng-Tongji cohort study. Smoking status was self-reported through questionnaire and occupational noise exposure was evaluated through workplace noise level and/or the job titles. Hearing loss was defined as a pure-tone mean of 25 dB or higher at 0.5, 1, 2, and 4 kHz in both ears. Compared with participants without occupational noise exposure, the risk of hearing loss was significantly higher for noise exposure duration ≥20 (OR = 1.45, 95%CI = 1.28–1.65). The association was particularly evident among individuals who were males (OR = 1.74, 95%CI = 1.45–2.08) and aged ≥ 70 (OR = 1.74, 95%CI = 1.30–2.33). Similarly, the risks increased with the increasing of pack-years in males and all age groups except for those aged <60. As to the combined effect, the hearing loss risk was highest for noise exposure duration ≥20 and pack-years ≥25 (OR = 2.41, 95%CI = 1.78–3.28), especially among males (OR = 2.42, 95%CI = 1.74–3.37) and those aged ≥70 (OR = 2.76, 95%CI = 1.36–5.60). Smoking may be an independent risk factor for hearing loss. And it may synergistically affect hearing when combined with occupational noise exposure, especially among males and older participants.

Microstructure evolution during hot deformation of a new Al-Zn-Mg-Cu alloy was investigated by Gleeble-1500D thermal -mechanical simulator at 300-450 degrees C and strain rate of 0. 001-10s(-1). The microstructure features at different hot deformation conditions were analyzed with optical microscope (OM) and transmission electron microscope (TEM). The results show that the dislocation density decreases and the subgrain sizes increase with the increase of deformation temperature and the decrease of the strain rate; the main softening mechanism of the alloy is dynamic recovery and dynamic recrystallization. Only dynamic recovery occurs when the temperature is 300-400 degrees C. Dynamic recrystallization occurs when the strain rate is 0. 001-10s(-1) at 450 degrees C. The nucleation mechanism is grain boundary bowing, subgrain growing and subgrain incorporation during dynamic recrystallization.