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Rationale and Objectives First, to evaluate and compare three different diffusion sequences (i.e., standard DWI, IVIM, and DKI) for nodal staging. Second, to combine the DWI, and anatomic information to assess metastatic lymph node (LN). Materials and Methods We retrospectively identified 136 patients of rectal adenocarcinoma who met the inclusion criteria. Three diffusion sequences (i.e., standard DWI, IVIM, and DKI) were performed, and quantitative parameters were evaluated. Univariate and multivariate analyses were used to assess the associations between the anatomic and DWI information and LN pathology. Multivariate logistic regression was used to identify independent risk factors. A nomogram model was established, and the model performance was evaluated by the concordance index (c-index) and calibration curve. Results There was a statistical difference in variables (LN long diameter, LN short diameter, LN boundary, LN signal, peri-LN signal intensity, ADC-1000, ADC-1400, ADC-2000, Kapp and D) between metastatic and non-metastatic LN for training and validation cohorts (p Conclusion The IVIM and DKI model's diagnostic efficiency was not significantly improved compared to conventional DWI. The diagnostic accuracy of metastatic LN can be enhanced using the nomogram model, leading to a rational therapeutic choice.

Ultrasonic testing procedures are among the most extensively used techniques in non-destructive testing and non-destructive evaluation systems. Meanwhile, phased array inspection or phased-array ultrasonic testing techniques as a well-known type of ultrasonic testing in advanced non-destructive testing systems are utilized in numerous applications, including oil and gas, medical imaging applications, railway, automotive, marine, and aviation industries. Phased-array ultrasonic testing-based methods can also be used in a variety of weld inspections, bond testing, thickness profiling, flaw detections, corrosion inspections, and in-service crack detection. The rapidity, safety, easiness, affordable price, and accurate visualization of phased array in measuring the defect characteristics such as size, shape, depth, and orientation allow its wide usage and even as a substitute for other inspection methods like radiographic methods. In phased array methods, more than one sound wave is employed to enhance the reliability and flexibility of inspection through the operation of several transducer assemblies, involving 16 to 256 small individual elements. Titanium having many desirable properties like high strength to weight ratio found many industrial applications, which highly necessitates its persistent inspection. For this aim, the present study focuses on the application of the phased-array ultrasonic testing technique for inspecting Ti components specifically in additive manufacturing, welding inspections, and defect detection of complex geometries and composites. Moreover, modern applications and improved computation methods are discussed. The development of phased-array ultrasonic testing inspection systems, particularly high throughput and efficient in situ and mobile equipment, and new computation methods will open new horizons toward the highly sophisticated inspection procedures.

Typhoons play an important role in beach evolution. The storm surge and large waves caused by typhoons can cause significant changes in beach morphology in a short period of time. The mechanism of beach evolution and profile changes during typhoons is significantly different from that under non-typhoon dynamic conditions. The XBeach numerical model provides an effective tool for predicting the response of sandy coasts to typhoons. This study is based on field-collected long-term beach profile elevations and grain size data, which were used to establish a two-dimensional XBeach model for simulating the morphological evolution of Cudao Island Beach under Typhoon Lekima. The GSA (Generalized Sensitivity Analysis) method was used to determine the sensitivity order of several important parameters in this modeling. Four different moments of wave height variation were selected during the typhoon process to analyze and study beach evolution. The results show that Chudao South Beach is always in a state of erosion during the typhoon period. The wave water increase is apparent in the nearshore wave-breaking area. The beach shoulder in the northeastern part of the beach is short, and the profile, with a short length, responds quickly to the typhoon. The eroded sediment is mainly deposited in the lower part of the intertidal zone or even transported outside of the wave-breaking zone, and a small part is transported to the shore and deposited in the high-tide zone. The continuous sediment transport along the coast of Chudao Beach is an important factor that influenced the evolution of each profile during Typhoon Lekima.

To develop novel wave energy conversion devices (WECDs) with excellent performance, the relative wave height and pressure in the chambers of square and curved oscillating water column (OWC) WECDs were compared through physical model tests, and the effects of regular incident wave factors, the opening length, the opening width, and the chamber volume on the aerodynamic performance and wave energy capture efficiency (WECE) of the WECDs were investigated. The results indicated good chamber performance for both the square and curved OWC WECDs. As the incident wave height increased, the wave surface elevation, WECE, and pressure in the chamber all increased, while the relative wave height in the chamber decreased. When the opening length, width, and area of the WECD increased, both the relative wave height and chamber pressure increased. The relative wave height in the chamber increased with decreasing chamber volume; however, the chamber pressure and intrachamber WECE decreased with increasing chamber volume. It is recommended that, in actual engineering applications, the overall efficiency of the device be improved by increasing the opening length, width, area and volume of the air chamber.

To compare the performance of CT and MRI radiomics for predicting the malignant potential of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to investigate their value compared to the revised 2017 international consensus Fukuoka guidelines.Sixty patients with surgically confirmed IPMNs (37 malignant and 23 benign) were included. Radiomics features were extracted from arterial and venous phase images of CT and T2-weighted images of MRI, respectively. Intraclass correlation coefficients for the radiomics features were calculated to assess the interobserver reproducibility. The least absolute shrinkage and selection operator algorithm was used for feature selection. Radiomics models were constructed based on selected features with logistic regression (LR) and support vector machine (SVM). A clinical and imaging model was constructed based on independent predictors of the revised 2017 Fukuoka guidelines determined in multivariate logistic regression with forward elimination.The reproducibility of MRI radiomics features was higher than that of CT radiomics features, regardless of arterial or venous phase features (all p0.001). MRI radiomics models achieved improved AUCs (0.879 with LR and 0.940 with SVM, respectively), than that of CT radiomics models (0.811 with LR and 0.864 with SVM, respectively). All radiomics models provided better predictive performance than the clinical and imaging model (AUC = 0.764).The MRI radiomics models with higher reproducibility radiomics features performed better than CT radiomics models for predicting the malignant potential of IPMNs. The performance of radiomics models was superior to the clinical and imaging model based on Fukuoka guidelines.

The response of beaches to typhoons has always been a hot topic at home and abroad. The study of beach changes during typhoons is helpful to deepen the understanding of beach evolution and is important for the coastal ecological environment. Based on the observation results of ten profiles and the sediment samples in Chudao before and after the typhoon Lekima, this article explored the response characteristics of the beach to the typhoon. The results showed that the study area was located on the right side of the typhoon’s forward path, and the double superposition of onshore waves and storm surge resulted in erosion along the beach. In order to alleviate the energy brought by storm waves, the beach was transformed into a more dissipated state. The mean particle size of the beach sediments was coarse on the whole, with poor sorting ability, and that in the wash zone was particularly obvious. The results showed that different profiles responded to Lekima in different ways: while the profiles of N01–N05 in the southwest changed little, those of N06–N10 in the northeast changed from the type of beach shoulder to the type of sandbank as a result of morphological differences in different profiles.

Gradient materials can achieve both external strengthening and internal toughening, which has great potential to break the strong plastic tradeoff. Titanium carbide (TiC) particle is conducive to form a wearable surface in biomedical Titanium (Ti) alloy. In this work, gradient TiC/Ti6Al4V composites were successfully prepared by friction stir processing (FSP). Microstructure, texture and mechanical properties of the material were systematically characterized. Scanning electron microscopy (SEM) showed that the equiaxed grains near the machined surface were transformed into elongated grains inside. The results of energy spectrum analysis (EDS) showed that there was element aggregation near TiC particles. X-ray diffraction (XRD) indicated martensitic transformation in the stir zone and in the transition zone. The results of nano indentation showed that the hardness of stir zone was higher. In order to promote recrystallization and improve the hardness of the transition zone, high temperature rapid heat treatment was carried out after FSP. When the sample was heated at 700°C and cooled in the furnace, the hardness increased to the maximum. In the process of rapid heating, the dissolution of elements near TiC particles also led to the increase of hardness. This study provides a new idea for surface modification of gradient titanium alloy by using FSP method to improve its mechanical properties.

The switch from using only trivalent oral polio vaccine (tOPV) to sequential schedules combining inactivated poliovirus vaccine (IPV) and bivalent oral polio vaccine (bOPV) for polio vaccination will cause changes to mucosal immunity against polio in infants, which plays an important role in preventing the poliovirus spread. Here, we analyzed mucosal immunity against poliovirus in the intestine during different sequential vaccination schedules. We conducted clinical trials in Guangxi Province, China on 1,200 2-month-old infants who were randomly assigned to one of three vaccination schedule groups: IPV-bOPV-bOPV, IPV-IPV-tOPV, and IPV-IPV-bOPV, with vaccine doses administered at 8, 12, and 16 weeks of age. Stool samples were collected from 10% of participants in each group before administration of the second vaccine doses and at 1, 2, and 4 weeks after the administrations of the second and third vaccine doses. Immunoglobulin A (IgA) in the stool samples was measured to analyze the mucosal immune response in the intestine. Because of the absence of poliovirus type 2 in bOPV, the vaccination schedule of IPV-IPV-bOPV did not sufficiently raise intestinal mucosal immunity against poliovirus type 2, although some cross-immunity was seen. The level of intestinal mucosal immunity was related to shedding status; shedders could produce intestinal mucosa IgA more quickly. The intestinal mucosal immunity level was not related to serum neutralizing antibody level. In the combined sequential vaccination schedule of IPV and bOPV, the risk of circulating vaccine-derived poliovirus type 2 (cVDPV2) may be increased owing to insufficient intestinal mucosal immunity against poliovirus type 2.

Wave parameters, such as wave height and wave period, are important for human activities, such as navigation, ocean engineering and sediment transport, etc. In this study, wave data from six buoys around Chinese waters, are used to assess the quality of wave height and wave period in the ERA5 reanalysis of the European Centre for Medium-Range Weather Forecasts. Annual hourly data with temporal resolution are used. The difference between the significant wave height (SWH) of ERA 5 and that of the buoy varies from −0.35 m to 0.30 m for the three shallow locations; for the three deep locations, the variation ranges from −0.09 m to 0.09 m. The ERA5 SWH data show positive biases, indicating an overall overestimation for all locations, except for E2 and S1 where underestimation is observed. During the tropical cyclone period, a large (about 32%) underestimation of the maximum SWH in the ERA5 data is observed. Hence, the ERA5 SWH data cannot be used for design applications without site-specific validation. The difference between the annual wave period from ERA5 and the mean wave period from the buoys varies from −1.31s to 0.4s. Inter-comparisons suggest that the ERA5 dataset is consistent with the annual mean SWH. However, for the average period, the performance is not good, and half of the correlation coefficients in the four points are less 50%. Overall, the deep water area simulation effect is better than that in the shallow water.

Salinity in estuaries has an important influence on sediment deposition, delta formation, and fishery economy. The change of runoff in Yellow River (YR), which is the largest river along the Bohai Sea, has an important effect on the salinity of the sea, particularly in Laizhou Bay. In this study, measured runoff data in Lijin hydrological station from 1950 to 2018 are adopted to examine the change of YR runoff into the sea. The study concludes that the runoff of YR is distributed unevenly throughout the year and the amount of runoff mainly concentrates during the flood season. Results show a decreasing trend at a significant level of α=0.95, with a range of −6.17 × 109 m3 yr−1. Three groups of runoff are set by using the Finite-Volume Coastal Ocean Model numerical model to analyze the change of salinity in Laizhou Bay. These modeled effects were compared with water level observations made by Bayuquan, Tanggu, and Penglai gauge stations and salinity surveys conducted by Longkou gauge station. Model results and observations of salinity distributions and coastal water level showed good agreement. We can conclude that the distribution of salinity in Laizhou Bay is high in the east and low in the west. Furthermore, it responded quickly to the change of the runoff from YR. Under conditions of high river discharge, the low-salinity zone increased in horizontal direction and reached the bottom in vertical direction.

A highly sensitive fluorescent sensor ZnDN was designed, synthesized and used for tracking intracellular zinc ions in various living cells and direct imaging of prostatic tissue in mice. ZnDN was prepared from the heterocyclic-fused naphthalimide fluorophore, and the zinc receptor, N,N-bis(2-pyridylmethyl)ethylenediamine (BPEN). Upon addition of Zn2+ to the solutions of ZnDN, a remarkable fluorescence enhancement was observed, which could be attributed to the photo-induced electron transfer (PET) mechanism. Since ZnDN exhibited high sensitivity toward Zn2+ in phosphate buffer solution, with a limit of detection of 4.0 × 10−9 mol/L, it was further applied for the imaging of exogenous and endogenous Zn2+ in different living cells. Living cells imaging experiments suggested that ZnDN could image the changes of intracellular free zinc ions, and could be used for two-photon imaging. Moreover, flow cytometry suggested that ZnDN could distinguish cancerous prostate cells from normal cells. Animal experiments indicated that ZnDN had the potential in imaging prostate tissue in vivo.

Convolutional neural networks (CNN) are widely used deep learning frameworks and are applied in the field of face recognition, achieving outstanding results. The Macropixel comparison approach is a shallow mathematical approach that recognizes faces by comparing the original pixel blocks of face images. In this article, the authors are inspired by ideas of the currently popular deep neural network framework and introduce two features into the mathematical approach: deep overlap and weighted filter. The aim is to explore if the idea of deep learning could benefit mathematical recognition method, which might extend the scope of face recognition research. Results from the experiments show that the new proposed approach achieves markedly better recognition rates than the original macropixel methods.

One hallmark of solid tumors, regardless of its type or stage, is the existence of an unsual acidic microenvironment, which has been considered a specific and ideal target for cancer imaging. Therefore, we developed a pH-activatable nanoprobe GNPs-CKL-FA for near-infrared fluorescence (NIR) and computed tomography (CT) imaging of tumors. This nanoprobe consists of a near-infrared fluorophore (Cy5.5), a pH-sensitive ketal linker, and gold nanoparticles (GNPs) decorated with folates that could bind to tumor cells' surface receptors to promote cellular internalization. This ability of folate to mediate tumor targeting and accelerate internalization has been confirmed by in vitro experiments with HeLa cells. The fluorescence of the nanoprobes successfully activated by low intracellular pH, especially in more acidic organelles. Furthermore, fluorescence signals increased to a greater extent when the pH in tumors was lowered by injection of acetate buffer and isoproterenol. The CT contrast of GNPs-CKL-FA was obtained after administering intravenously to HeLa subcutaneous tumor-bearing mice. These results suggest that GNPs-CKL-FA has the potential to be a pH-activatable fluorescent nanoprobe combined with CT contrast agent for tumor targeted imaging.

Surface wind is significant for ocean state climate, ocean mixing, and viability of wind energy techniques. However, surface wind simulated from the regional climate model generally features substantial bias from observation. For the first time, this study compares the performance of five bias correction techniques, (1) linear scaling, (2) variance scaling, (3) quantile mapping based on empirical distribution, (4) quantile mapping based on Weibull distribution, and (5) cumulative distribution functions transformation, in reducing the statistical bias of a regional climate model wind output, which was downscaled from a global climate model CNRM-CM5 during 1991-2000. The surface wind of JRA55 reanalysis data is used as reference. Results show that all bias correction methods are consistent in reducing the climatological mean bias in spatial patterns and intensities. The linear scaling method always performs the worst among all methods in correcting higher-order statistical biases such as skewness, kurtosis, and wind power density. The other four bias correction methods are generally similar in reducing the statistical biases of different measures based on spatial distribution maps. However, when it comes to spatial averaged mean of statistical measures over CORDEX-East Asia in January and July, the quantile mapping based on Weibull distribution generally shows the best skills among all methods in bias reduction. Plain Language Summary In the current stage, global climate model or regional climate model simulations generally feature substantial bias relative to observations, leading to an inaccurate assessment of climate change or inaccurate inputs for impact models. For the first time, we have compared five bias correction methods using various statistical measures to find out the most robust method for correcting statistical properties of simulated winds from regional climate model. Results show that the linear scaling method always performs the worst among all methods in correcting higher-order statistical biases of simulated winds. On average, the quantile mapping based on Weibull distribution shows the best skills among all methods in bias reduction in January and July. This study is of importance for climate change assessment of wind as well as deriving accurate wind forcing for driving ocean model.

Due to the growing aging population of the world, and as a result of the increasing need for dental implants and prostheses, the use of titanium and its alloys as implant materials has spread rapidly. Although titanium and its alloys are considered the best metallic materials for biomedical applications, the need for innovative technologies is necessary due to the sensitivity of medical applications and to eliminate any potentially harmful reactions, enhancing the implant-to-bone integration and preventing infection. In this regard, the implant’s surface as the substrate for any reaction is of crucial importance, and it is accurately addressed in this review paper. For constructing this review paper, an internet search was performed on the web of science with these keywords: surface modification techniques, titanium implant, biomedical applications, surface functionalization, etc. Numerous recent papers about titanium and its alloys were selected and reviewed, except for the section on forthcoming modern implants, in which extended research was performed. This review paper aimed to briefly introduce the necessary surface characteristics for biomedical applications and the numerous surface treatment techniques. Specific emphasis was given to micro/nano-structured topographies, biocompatibility, osteogenesis, and bactericidal effects. Additionally, gradient, multi-scale, and hierarchical surfaces with multifunctional properties were discussed. Finally, special attention was paid to modern implants and forthcoming surface modification strategies such as four-dimensional printing, metamaterials, and metasurfaces. This review paper, including traditional and novel surface modification strategies, will pave the way toward designing the next generation of more efficient implants.

Functional gradient materials (FGMs), as a modern group of materials, can provide multiple functions and are able to well mimic the hierarchical and gradient structure of natural systems. Because biomedical implants usually substitute the bone tissues and bone is an organic, natural FGM material, it seems quite reasonable to use the FGM concept in these applications. These FGMs have numerous advantages, including the ability to tailor the desired mechanical and biological response by producing various gradations, such as composition, porosity, and size; mitigating some limitations, such as stress-shielding effects; improving osseointegration; and enhancing electrochemical behavior and wear resistance. Although these are beneficial aspects, there is still a notable lack of comprehensive guidelines and standards. This paper aims to comprehensively review the current scenery of FGM metallic materials in the biomedical field, specifically its dental and orthopedic applications. It also introduces various processing methods, especially additive manufacturing methods that have a substantial impact on FGM production, mentioning its prospects and how FGMs can change the direction of both industry and biomedicine. Any improvement in FGM knowledge and technology can lead to big steps toward its industrialization and most notably for much better implant designs with more biocompatibility and similarity to natural tissues that enhance the quality of life for human beings.

To investigate the value of radiomic features at contrast-enhanced CT integrated with clinic-pathologic features and body composition measures for predicting survival after upfront surgery in patients with pancreatic ductal adenocarcinoma (PDAC).Two hundred and ninety-nine patients with PDAC who underwent surgical resection were included and allocated to training set (210 patients) and validation set (89 patients). The radiomics signature for predicting survival was constructed by using the least absolute shrinkage and selection operator Cox regression. Multivariable Cox regression analysis was used to construct a radiomics model based on radiomics signature, clinic-pathologic features and body composition measures. A clinical model without radiomics signature was also developed. Model performance was analyzed by Harrell's concordance index (C-index) and time-independent receiver operating characteristic (ROC) analysis. The Kaplan-Meier (KM) method was used for survival analysis.Five independent variables were selected for the radiomics model: radiomics signature, carbohydrate antigen 19-9, skeletal muscle index, histologic grade and postoperative chemotherapy. The radiomics-based model provided better predictive performance (C-index = 0.73; all p 0.05) than the clinical model without radiomics signature and American Joint Committee on Cancer (AJCC) TNM staging system. Patients were stratified as high-risk and low-risk group by the radiomics model. The KM analysis showed a significant difference between two groups (p 0.05).The radiovdmics-based model integrating with clinic-pathologic features and body composition measures could predict survival after surgical resection in PDAC patients.

Pancreatic cancer severely affects people's wellbeing and has been one of the most malignant digestive diseases with regard to its tough diagnosis and treatment. Recently many papers have focused on the utility of siRNA as potential therapeutics to cure tumors. Herein, we developed a novel siRNA nanocarrier based on biomimetic Au@BSA nanoflowers that might be applied as a potential theranostic nanoplatform. As gold has a much larger atomic number and X-ray absorption coefficient in comparison with traditional iodine agents, it is suitable to utilize the nanoprobe for computed tomography (CT) as well as optical multimodal imaging when combined with fluorescence markers. Firstly, Au@BSA nanoflowers were obtained utilizing bovine serum albumin (BSA) as a biotemplate. Then the synthesized Au@BSA nanocomposites were conjugated with siRNA-FAM to form Au@BSA–siRNA-FAM through electrostatic layer-by-layer assembling interactions. The constructed delivery system showed good biocompatibility due to the BSA coating. Furthermore, the in vitro experiments demonstrated that the delivered siRNA could efficiently suppress the growth of BXPC-3 cells through gene silencing. In general, the biomimetic Au@BSA nanocarrier may provide a new method for cancer therapy.

Serum albumins perform various biological functions in bioorganisms, and abnormal levels of serum albumin are predictors of many diseases; contrary to the various approaches developed for the detection of serum albumins in blood and urine samples, limited tools are available for tracing and exploring endogenous serum albumins in living bioorganisms. Specifically, fluorescent probes have not been used for the exploration of endogenous serum albumins in zebrafish. Herein, we presented a versatile fluorescent probe (C7H) that highly specifically interacted with the site I of serum albumins. We succeeded in developing C7H as a visualized tool for tracing endogenous serum albumins in living larval zebrafish. Furthermore, C7H could be used as a fluorescent probe for the real-time monitoring of the wound area in larval zebrafish. Our results suggest that the larval zebrafish has a strong self-repair capacity for wound areas. Thus, C7H could be an efficient probe for studying wound healing in live zebrafish. Moreover, C7H can significantly expand the further understanding of wound healing in zebrafish, which may also promote the research on wound healing in human beings.

In this study, we investigate the skills of the regional climate model Consortium for Small-Scale Modeling in Climate Mode (CCLM) in reproducing historical climatic features and their added value to the driving global climate models (GCMs) of the Coordinated Regional Climate Downscaling Experiment—East Asia (CORDEX-EA) domain. An ensemble of climate simulations, with a resolution of 0.44°, was conducted by downscaling four GCMs: CNRM-CM5, EC-EARTH, HadGEM2, and MPI-ESM-LR. The CCLM outputs were compared with different observations and reanalysis datasets. Results showed strong seasonal variability of CCLM’s ability in reproducing climatological means, variability, and extremes. The bias of the simulated summer temperatures is generally smaller than that of the winter temperatures; in addition, areas where CCLM adds value to the driving GCMs in simulating temperature are larger in the winter than in the summer. CCLM outperforms GCMs in terms of generating climatological precipitation means and daily precipitation distributions for most regions in the winter, but this is not always the case for the summer. It was found that CCLM biases are partly inherited from GCMs and are significantly shaped by structural biases of CCLM. Furthermore, downscaled simulations show added value in capturing features of consecutive wet days for the tropics and of consecutive dry days for areas to the north of 30°N. We found considerable uncertainty from reanalysis and observation datasets in temperatures and precipitation climatological means for some regions that rival bias values of GCMs and CCLM simulations. We recommend carefully selecting reference datasets when evaluating modeled climate means.

Shi, H.Y.; You, Z.J.; Yin, B.S., and Bai, Y.C., 2018. Critical Depths Derived for Three Distinct Modes of Coastal Sediment Transport. In: Shim, J.-S.; Chun, I., and Lim, H.S. (eds.), Proceedings from the International Coastal Symposium (ICS) 2018 (Busan, Republic of Korea). Journal of Coastal Research, Special Issue No. 85, pp. 271–275. Coconut Creek (Florida), ISSN 0749-0208.A unified criterion is developed for three distinct modes of coastal sediment transport: incipient movement of sediment (only bedload), initiation of bedripple formation (bedload and suspended load), and inception of bed ripple disappearance or sheet flow (mainly bed load) based on three unique laboratory datasets collected on a horizontal bed of sediment under regular waves. The onset velocity criterion on the three distinct sediment transport modesis derived to be of the same simple form, U0 = 2πC (1 − T0/T), where U0 is the maximum on set wave orbital velocity close to the bed, T is the wave period, and C and T0 are the coefficients dependent of sediment property only. The newly developed criterion is then extended to calculate critical depths for the distinct modes of sediment transport under coastal waves by replacing regular wave height H and period T with statistical wave height Hrms and period Trms according to the recently developed “zero-crossing and energy balance” wave analysis method and linear wave theory. The critical depth calculated from this unified criterion is shown to be a function of sediment grain size and density, and wave height and period, but more sensitive to wave period. The critical depth estimated for the initiation of bed sediment ripple formation is found to be much larger than the depth of closure derived for beach-fill designs.

For the urgent need for fermentation control and product quality improvement of Pu-erh tea, gas chromatography-mass spectrometry and odor activity value (OAV) were used to comprehensively investigate the flavor-active compounds during artificial fermentation of Pu-erh tea. A flavor wheel was constructed to expound the sensory attributes evolution during fermentation. With an increased total volatiles content, 43 were significantly up-regulated and 30 were down-regulated among 131 detected volatiles. Key active compounds of three aroma types, namely fresh fragrance, fruit-fungus fragrance and stale-Qu fragrance, were analyzed based on OAV. β-damascenone was firstly found contributing most to the aroma of Pu-erh tea, followed by 1,2,3-methoxybenzene and (E,E)-2,4-nonadienal. γ-terpinene, linalool, 1,2,4-trimethoxybenzene, 1,2,3-trimethoxybenzene, and 4-ethylveratrol were identified as the potential markers responsible for aroma differences among three fermentation stages. Finally the metabolic evolution of key flavor-active compounds were systematically summarized. This study provides significant guidance in fermentation control and new product development of Pu-erh tea.