Comparative effectiveness of multiple androgen receptor signaling inhibitor medicines with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer: a study in the real world.

Background: The current treatment strategy for metastatic Hormone-Sensitive Prostate Cancer (mHSPC) is the combination of Androgen Receptor Signaling Inhibitors (ARSIs) medicines with androgen deprivation therapy (ADT). However, there is a lack of real-world data comparing the efficacy of different ARSI pharmaceuticals. Therefore, the objective of this study was to compare the effectiveness and safety of bicalutamide, abiraterone, enzalutamide, and apalutamide in combination with ADT for patients with mHSPC. Methods: We retrospectively analyzed 82 patients diagnosed with mHSPC, including 18 patients treated with abiraterone acetate with prednisone, 21 patients with enzalutamide, 20 patients with apalutamide, and 23 patients with bicalutamide. We evaluated PSA progression-free survival (PSA-PFS), imaging progression-free survival (r PFS), castration resistance progression-free survival (CRPC-PFS), and overall survival (OS) using Kaplan-Meier survival analyses. Additionally, we explored relevant factors affecting prognosis through univariate and multivariate Cox risk-proportionality models. PSA response rates at 3, 6, and 12 months, nadir PSA levels (nPSA), and time to nadir (TTN) in different medication subgroups after treatment were documented, and we used one-way ANOVA to determine the effect of these measures on patient prognosis. Results: In comparison with bicalutamide, both enzalutamide and apalutamide have shown significant advantages in delaying disease progression among mHSPC patients. Specifically, enzalutamide has been found to significantly prolong PSA-PFS (HR 2.244; 95% CI 1.366-3.685, p=0.001), rPFS (HR 2.539; 95% CI 1.181-5.461; p= 0.007), CRPC-PFS (HR 2.131; 95% CI 1.295-3.506; p= 0.003), and OS (HR 2.06; 95% CI 1.183-3.585; P=0.005). Similarly, apalutamide has significantly extended PSA-PFS (HR 5.071; 95% CI 1.711-15.032; P= 0.003) and CRPC-PFS (HR 6.724; 95% CI 1.976-22.878; P=0.002) among patients. On the other hand, the use of abiraterone in combination with ADT did not demonstrate a significant advantage in delaying diseases progression when compared with the other three agents in mHSPC patients. There were no significant differences in overall adverse event rates among the four pharmaceuticals in terms of safety. Additionally, the observation of PSA kinetics revealed that enzalutamide, apalutamide, and abiraterone acetate had a significant advantage in achieving deep PSA response (PSA ≤ 0.2 ng/ml) compared with bicalutamide (p=0.007 at 12 months). Enzalutamide and apalutamide exhibited preeminence efficacy, with no substantial difference observed between the two medications. Conclusions: Abiraterone, enzalutamide, and apalutamide were found to significantly reduce and stabilize PSA levels in mHSPC patients more quickly and thoroughly than bicalutamide. Furthermore, enzalutamide and apalutamide were found to significantly prolong survival and delay disease progression in mHSPC patients compared with bicalutamide. It should be noted that abiraterone did not demonstrate a significant advantage in delaying disease compared with enzalutamide and apalutamide. After conducting drug toxicity analyses, it was determined that there were no significant differences among the four drugs.

Research on the spatial correlation and formation mechanism between traditional villages and rural tourism.

In recent years, the survival and development of traditional villages in China have been serious challenges. Rural tourism is regarded as an important way to solve rural problems, and the combination of rural culture and tourism has become a new power point for rural development. Therefore, it is necessary to explore the spatial distribution structure between traditional villages and rural tourism. In this paper, rural tourism was represented by the rural tourism characteristic village (RTCV), and Henan Province, China, was taken as a study area to analyze the distribution pattern and spatial correlation of rural tourism and traditional village (TV) and discuss the relationship between the spatial correlation and regional natural environment and socioeconomic factors. The results show that the coupling of the spatial correlation between RTCVs and TVs in Henan was clear. They could be divided into 5 regions based on geographical factors. In addition, the research summarized 4 typical spatial structures between TVs and RTCVs in Henan based on the regional symbiosis theory, and the spatial pattern formation mechanism of TVs and RTCVs was discussed based on three driving mechanisms. The spatial structure of the two can provide reference value for other developing countries and regions to achieve sustainable rural development.

Self-Weighted Unsupervised LDA.

As a hot topic in unsupervised learning, clustering methods have been greatly developed. However, the model becomes more and more complex, and the number of parameters becomes more and more with the continuous development of clustering methods. And parameter-tuning in most methods is a laborious work due to its complexity and unpredictability. How to propose a concise and beautiful model in which the parameters can be learned adaptively becomes a very meaningful problem. Aim at tackling this problem, we develop a novel self-weighted unsupervised linear discriminative analysis method, namely SWULDA. The proposed method not only avoids adjusting parameters but also explains the link between k -means and linear discriminant analysis (LDA). To obtain superior structural performance, the idea of minimizing the within-class scatter matrix and maximizing the between-class scatter matrix is embedded in the unsupervised model. Moreover, equipped with the proposed quadratic weighted optimization framework, the parameter can be adaptively learned. The extensive experiments on several datasets are conducted to validate the effectiveness of our method.

Unsupervised Graph Embedding via Adaptive Graph Learning.

Graph autoencoders (GAEs) are powerful tools in representation learning for graph embedding. However, the performance of GAEs is very dependent on the quality of the graph structure, i.e., of the adjacency matrix. In other words, GAEs would perform poorly when the adjacency matrix is incomplete or be disturbed. In this paper, two novel unsupervised graph embedding methods, unsupervised graph embedding via adaptive graph learning (BAGE) and unsupervised graph embedding via variational adaptive graph learning (VBAGE) are proposed. The proposed methods expand the application range of GAEs on graph embedding, i.e, on the general datasets without graph structure. Meanwhile, the adaptive learning mechanism can initialize the adjacency matrix without being affected by the parameter. Besides that, the latent representations are embedded with the Laplacian graph structure to preserve the topology structure of the graph in the vector space. Moreover, the adjacency matrix can be self-learned for better embedding performance when the original graph structure is incomplete. With adaptive learning, the proposed method is much more robust to the graph structure. Experimental studies on several datasets validate our design and demonstrate that our methods outperform baselines by a wide margin in node clustering, node classification, link prediction, and graph visualization tasks.

The roles of lncRNA functions and regulatory mechanisms in the diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most frequent and deadly type of liver cancer. While the underlying molecular mechanisms are poorly understood, it is documented that lncRNAs may play key roles. Many HCC-associated lncRNAs have been linked to HBV and HCV infection, mediating gene expression, cell growth, development, and death. Studying the regulatory mechanisms and biological functions of HCC-related lncRNAs will assist our understanding of HCC pathogenesis as well as its diagnosis and management. Here, we address the potential of dysregulated lncRNAs in HCC as diagnostic and therapeutic biomarkers, and we evaluate the oncogenic or tumor-suppressive properties of these lncRNAs.

Research on the Vitality Evaluation of Parks and Squares in Medium-Sized Chinese Cities from the Perspective of Urban Functional Areas.

Medium-sized cities are increasingly committed to the planning and construction of urban public spaces to meet people's demand for high-quality urban life. Parks and squares are important parts of urban public spaces, and their vitality represents the quality of public spaces to a certain extent and reflects the happiness index of urban residents. At present, the functional areas and transportation networks of medium-sized cities are still developing. Due to the influence of urban construction, the planning of parks and squares in medium-sized cities has not yet caught up to that in larger cities. This study analyzed a medium-sized city, Jiaozuo, as an example, with the help of point of interest (POI) data, OpenStreetMap road network density data and WorldPop population data. The vitality of parks and squares in different functional spaces in the main urban area in Jiaozuo was quantitatively evaluated in terms of the four following aspects: urban space functional area characteristics, travel vitality index of urban residents, park and square attractiveness and the regional service levels of parks and squares. The effects of functional mixing, traffic network density, population density and spatial distribution on the vitality of parks and squares in medium-sized cities were also studied. The results showed that (1) the functional mixing in the main urban area in Jiaozuo was characterized by a spatial distribution of high in the center and low in the surrounding areas, with the highest functional mixing in the central part of the Jiefang District; (2) the travel dynamics of urban residents were characterized by a clear development of concentric circles radiating in a circular pattern; (3) the levels of service in parks and squares were particularly high in Jiefang District, with a spatial distribution of Jiefang District > Shanyang District > Macun District > Zhongzhan District; (4) under the condition that the service levels of each district were the same, the vitality values of the existing parks and squares in each district were compared and, from high to low, were Jiefang District (1.0-3.5), Shanyang District (0.2-2.0), Macun District (0-1.4) and Zhongzhan District (0-1.2). Functional mixing, road networks and population density had significant impacts on the vitality of parks and squares. Based on our study on the division of urban functional areas, we expanded the study to include urban microspaces. By evaluating the vitality of existing parks and squares and analyzing the influencing factors of spatial vitality, we found that it would be helpful to adopt targeted strategies to improve spatial vitality. Considering the spatial layouts of parks and squares, planning and constructing high-vitality parks and squares would be conducive to the future development of medium-sized cities. The existence of high-vitality spaces could also help to realize the sustainable development of cities.

Unsupervised Feature Selection via Adaptive Graph Learning and Constraint.

The performance of graph-based feature selection methods relies heavily on the quality of the construction of the similarity matrix. However, most of the graphs on these methods are initially fixed, where few of them are constrained. Once the graph is determined, it will remain constant in the whole optimization process. In other words, in case that the graph constructed on the raw data is not appropriate, it will drag down the entire algorithm. Aiming to tackle this defect, a novel unsupervised feature selection via adaptive graph learning and constraint (EGCFS) is proposed to select the uncorrelated yet discriminative features by exploiting the embedded graph learning and constraint. The adaptive graph learning method incorporates the structure of the similarity matrix into the optimization process, which not only learns the graph structure adaptively but also obtains the closed-form solution of the graph coefficient. Special graph constraint is embedded with the feature selection process to connect nearer data points with larger probability. The idea of maximizing between-class scatter matrix and the adaptive graph structure is integrated into a uniform framework to obtain excellent structural performance. Moreover, the proposed embedded graph constraint not only performs with manifold structure but also validates the link between graph-based approach and k -means from a unique perspective. Experiments on several benchmark data sets verify the effectiveness and superiority of the proposed method.

Semisupervised Feature Selection via Generalized Uncorrelated Constraint and Manifold Embedding.

Ridge regression is frequently utilized by both supervised learning and semisupervised learning. However, the results cannot obtain the closed-form solution and perform manifold structure when ridge regression is directly applied to semisupervised learning. To address this issue, we propose a novel semisupervised feature selection method under generalized uncorrelated constraint, namely SFS. The generalized uncorrelated constraint equips the framework with the elegant closed-form solution and is introduced to the ridge regression with embedding the manifold structure. The manifold structure and closed-form solution can better save data's topology information compared to the deep network with gradient descent. Furthermore, the full rank constraint of the projection matrix also avoids the occurrence of excessive row sparsity. The scale factor of the constraint that can be adaptively obtained also provides the subspace constraint more flexibility. Experimental results on data sets validate the superiority of our method to the state-of-the-art semisupervised feature selection methods.

Nickel-Catalyzed Carboalkenylation of 1,3-Dienes with Aldehydes and Alkenylzirconium Reagents: Access to Skipped Dienes.

A regio- and stereoselective nickel-catalyzed three-component coupling reaction of aldehydes, 1,3-dienes, and alkenylzirconium reagents was realized. The ligand- and additive-free protocol afforded a convenient approach to the synthesis of skipped diene compounds bearing various functionals (e.g., hydroxyl, carbonyl, halide) and heterocyclic groups. The products were readily transformed into structurally diverse polyenes. The utility of this reaction was also demonstrated by the one-pot operation and scale-up preparation.

Effects of growth irradiance on photosynthesis and photorespiration of Phoebe bournei leaves.

Light intensity is a major environmental factor affecting the growth and survival of trees in a forest. The effect of light reduction on photosynthesis and photorespiration of an evergreen broad-leaved tree, Phoebe bournei (Hemsley) Yang was examined with three levels of full light, 50.5% light, and 21.8% light. The results showed that shading led to significant increase in plant height and crown diameter. Light-saturated leaf photosynthetic rate (Amax), maximal carboxylation activity (Vcmax), maximum electron transfer rate (Jmax), stomatal conductance (gs), mesophyll conductance (gm) and chloroplast CO2 concentration (Cc) significantly increased in response to shade. Photorespiratory CO2 release rate (PR) was higher in plants grown under shade conditions than under full light. The relative limitations of gm (lm) was higher than the relative limitations of gs (ls) and the relative limitations of biochemical factors (lb) in leaves of P. bournei grown under full light, whereas lm was lower than ls and lb under shade. Our results suggest that increase of photosynthesis in P. bournei leaves grown under shade is associated with enhanced CO2 diffusion and biochemistry. And we propose that enhancement of the photorespiratory is essential for shade leaves to improve photosynthesis.

SaHsfA4c From Sedum alfredii Hance Enhances Cadmium Tolerance by Regulating ROS-Scavenger Activities and Heat Shock Proteins Expression.

The heat shock transcription factor (Hsf) family, an important member in plant stress response, affects cadmium (Cd) tolerance in plants. In this study, we identified and functionally characterized a transcript of the Hsf A4 subgroup from Sedum alfredii. Designated as SaHsfA4c, the open reading frame was 1,302 bp long and encoded a putative protein of 433 amino acids containing a complete DNA-binding domain (DBD). Heterologous expression of SaHsfA4c in yeast enhanced Cd stress tolerance and accumulation, whereas expression of the alternatively spliced transcript InSaHsfA4c which contained an intron and harbored an incomplete DBD, resulted in relatively poor Cd stress tolerance and low Cd accumulation in transgenic yeast. The function of SaHsfA4c under Cd stress was characterized in transgenic Arabidopsis and non-hyperaccumulation ecotype S. alfredii. SaHsfA4c was able to rescue the Cd sensitivity of the Arabidopsis athsfa4c mutant. SaHsfA4c reduced reactive oxygen species (ROS) accumulation and increased the expression of ROS-scavenging enzyme genes and Hsps in transgenic lines. The present results suggest that SaHsfA4c increases plant resistance to stress by up-regulating the activities of ROS-scavenging enzyme and the expression of Hsps.

Transporters and ascorbate-glutathione metabolism for differential cadmium accumulation and tolerance in two contrasting willow genotypes.

Salix matsudana Koidz is a low cadmium (Cd)-accumulating willow, whereas its cultivated variety, Salix matsudana var. matsudana f. umbraculifera Rehd., is a high Cd-accumulating and tolerant willow (HCW). The physiological and molecular mechanisms underlying differential Cd accumulation and tolerance in the two Salix species are poorly understood. Here, we confirmed that the differential Cd translocation capacity from roots to the shoots leads to the differential Cd accumulation in their aboveground parts between these two willow genotypes. Cadmium accumulation happens preferentially in the transport pathway, and Cd is mainly located in the vacuolar, cell wall and intercellular space in HCW bark by cadmium location analysis at tissue and subcellular levels. Comparative transcriptome analysis revealed that higher expressions of several metal transporter genes (ATP-binding cassette transporters, K+ transporters/channels, yellow stripe-like proteins, zinc-regulated transporter/iron-regulated transporter-like proteins, etc.) are involved in root uptake and translocation capacity in HCW; meanwhile, ascorbate-glutathione metabolic pathways play essential roles in Cd detoxification and higher tolerance of the Cd-accumulator HCW. These results lay the foundation for further understanding the molecular mechanisms of Cd accumulation in woody plants and provide new insights into molecular-assisted-screening woody plant varieties for phytoremediation.

Identification, Expression Analysis of the Hsf Family, and Characterization of Class A4 in Sedum Alfredii Hance under Cadmium Stress.

Sedum alfredii Hance, a cadmium (Cd)/zinc (Zn)/lead (Pb) co-hyperaccumulating species, is a promising phytoremediation candidate because it accumulates substantial amounts of heavy metal ions without showing any obvious signs of poisoning. The heat shock transcription factor (Hsf) family plays crucial roles in plant growth, development, and stress responses. Although the roles of some Hsfs in abiotic stress have been well studied in model plants, the Hsf family has not been systematically investigated in heavy metal hyperaccumulators. Here, we comprehensively analyzed the Hsf gene family in S. alfredii based on a transcriptome under Cd stress. There were 22 Hsf members that were identified and phylogenetically clustered into three classes, namely, SaHsfA, SaHsfB, and SaHsfC. All of the three classes shared similar motifs. The expression profiles of the 22 Hsf members showed significant differences: 18 SaHsfs were responsive to Cd stress, as were multiple SaHsp genes, including SaHsp18.1, SaHsp22, SaHsp26.5, SaHsp70, SaHsp90, and SaHsp101. Two class A4 members, SaHsfA4a and SaHsfA4c, exhibited transcriptional activation activities. Overexpression of SaHsfA4a and SaHsfA4c in transgenic yeast indicated an improved tolerance to Cd stress and Cd accumulation. Our results suggest SaHsfs play important regulatory roles in heavy metal stress responses, and provide a reference for further studies on the mechanism of heavy metal stress regulation by SaHsfs.

LncRNA CBR3-AS1 predicts unfavorable prognosis and promotes tumorigenesis in osteosarcoma.

LncRNA CBR3-AS1 has been suggested to promote malignancy in several types of human cancers, but the clinical significance and biological function of lncRNA CBR3-AS1 in osteosarcoma is still unknown. The purpose of our study is to explore the clinical significance of lncRNA CBR3-AS1 in osteosarcoma patients and the biological function in osteosarcoma cells. In our results, we found lncRNA CBR3-AS1 was highly-expressed in osteosarcoma tissues and cell lines, and associated with Enneking stage, distant metastasis and histological grade. Survival analysis indicated that the high-expression of lncRNA CBR3-AS1 was an independent poor prognostic factor for osteosarcoma patients. Loss-of-function studies showed knockdown of lncRNA CBR3-AS1 suppressed osteosarcoma cells proliferation, migration and invasion, and promotes cells apoptosis, but had no effect on cell-cycle distribution. There was no association between lncRNA CBR3-AS1 and CBR3 expression in osteosarcoma tissues, and knockdown of lncRNA CBR3-AS1 had no effect on CBR3 mRNA and protein expression osteosarcoma cells. In conclusion, lncRNA CBR3-AS1 serves an oncogenic role to regulate osteosarcoma cells proliferation, migration, invasion and apoptosis, and is an independent poor prognostic factor for osteosarcoma patients.

A comprehensive genome-wide analysis of long noncoding RNA expression profile in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, especially in East Asia and China. Long noncoding RNAs (lncRNAs) are emerging as critical regulators that may be involved in the development and progression of cancers in humans. However, the contributions of lncRNAs to HCC development, metastasis, and recurrence remain largely unknown. In this study, we comprehensively investigated lncRNA expression profile in HCC and normal tissues using TCGA RNA sequencing data, one RNA sequencing dataset, and two microarray datasets from GEO. By analyzing these four datasets, we identified hundreds of expression-dysregulated lncRNAs in HCC tissues compared with normal tissues. Genomic copy number variation analysis showed that many of those lncRNAs disorder are related to the copy number amplification or deletion. Moreover, several lncRNAs expression levels are associated with HCC patients' overall and recurrence-free survival, such as RP1-228H13.5, TMCC1-AS1, LINC00205, and RP11-307C12.11. Furthermore, we identified two lncRNAs termed PVT1 and SNHG7 that may be involved in HCC cells metastasis by comparing lncRNAs expression profiles between early recurrence HCC tissues with metastasis and late recurrence HCC tissues without metastasis. Finally, loss-of-function assays confirmed that knockdown of SNHG7 and PVT1 impaired HCC cells invasion. Taken together, these findings may provide a valuable resource for further identification of novel biomarkers and therapeutic targets for HCC patients.

Overexpressing the Sedum alfredii Cu/Zn Superoxide Dismutase Increased Resistance to Oxidative Stress in Transgenic Arabidopsis.

Superoxide dismutase (SOD) is a very important reactive oxygen species (ROS)-scavenging enzyme. In this study, the functions of a Cu/Zn SOD gene (SaCu/Zn SOD), from Sedum alfredii, a cadmium (Cd)/zinc/lead co-hyperaccumulator of the Crassulaceae, was characterized. The expression of SaCu/Zn SOD was induced by Cd stress. Compared with wild-type (WT) plants, overexpression of SaCu/Zn SOD gene in transgenic Arabidopsis plants enhanced the antioxidative defense capacity, including SOD and peroxidase activities. Additionally, it reduced the damage associated with the overproduction of hydrogen peroxide (H2O2) and superoxide radicals (O2•-). The influence of Cd stress on ion flux across the root surface showed that overexpressing SaCu/Zn SOD in transgenic Arabidopsis plants has greater Cd uptake capacity existed in roots. A co-expression network based on microarray data showed possible oxidative regulation in Arabidopsis after Cd-induced oxidative stress, suggesting that SaCu/Zn SOD may participate in this network and enhance ROS-scavenging capability under Cd stress. Taken together, these results suggest that overexpressing SaCu/Zn SOD increased oxidative stress resistance in transgenic Arabidopsis and provide useful information for understanding the role of SaCu/Zn SOD in response to abiotic stress.

Selection of suitable reference genes for quantitative real-time PCR gene expression analysis in Salix matsudana under different abiotic stresses.

Salix matsudana is a deciduous, rapidly growing willow species commonly cultivated in China, which can tolerate drought, salt, and heavy metal stress conditions. Selection of suitable reference genes for quantitative real-time PCR is important for normalizing the expression of the key genes associated with various stresses. To validate suitable reference genes, we selected 11 candidate reference genes (five traditional housekeeping genes and six novel genes) and analyzed their expression stability in various samples, including different tissues and under different abiotic stress treatments. The expression of these genes was determined using five programs-geNorm, NormFinder, BestKeeper, ΔCt, and RefFinder. The results showed that α-TUB2 (alpha-tubulin 2) and DnaJ (chaperone protein DnaJ 49) were the most stable reference genes across all the tested samples. We measured the expression profiles of the defense response gene SmCAT (catalase) using the two most stable and one least stable reference genes in all samples of S. matsudana. The relative quantification of SmCAT varied greatly according to the different reference genes. We propose that α-TUB2 and DnaJ should be the preferred reference genes for normalization and quantification of transcript levels in future gene expression studies in willow species under various abiotic stress conditions.

Transcriptome analysis of immature xylem in the Chinese fir at different developmental phases.

Background.Chinese fir [Cunninghamia lanceolata (Lamb.) Hook.] is one of the most important native tree species for timber production in southern China. An understanding of overall fast growing stage, stem growth stage and senescence stage cambium transcriptome variation is lacking. We used transcriptome sequencing to identify the repertoire of genes expressed during development of xylem tissue in Chinese fir, aiming to delineate the molecular mechanisms of wood formation. Results. We carried out transcriptome sequencing at three different cultivation ages (7Y, 15Y and 21Y) generating 68.71 million reads (13.88 Gbp). A total of 140,486 unigenes with a mean size of 568.64 base pairs (bp) were obtained via de novo assembly. Of these, 27,427 unigenes (19.52%) were further annotated by comparison to public protein databases. A total of 5,331 (3.79%) unigenes were mapped into 118 pathways by searching against the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG). Differentially expressed genes (DEG) analysis identified 3, 16 and 5,899 DEGs from the comparison of 7Y vs. 15Y, 7Y vs. 21Y and 15Y vs. 21Y, respectively, in the immature xylem tissues, including 2,638 significantly up-regulated and 3,280 significantly down-regulated genes. Besides, five NAC transcription factors, 190 MYB transcription factors, and 34 WRKY transcription factors were identified respectively from Chinese fir transcriptome. Conclusion. Our results revealed the active transcriptional pathways and identified the DEGs at different cultivation phases of Chinese fir wood formation. This transcriptome dataset will aid in understanding and carrying out future studies on the molecular basis of Chinese fir wood formation and contribute to future artificial production and applications.

Integration of small RNAs, degradome and transcriptome sequencing in hyperaccumulator Sedum alfredii uncovers a complex regulatory network and provides insights into cadmium phytoremediation.

The hyperaccumulating ecotype of Sedum alfredii Hance is a cadmium (Cd)/zinc/lead co-hyperaccumulating species of Crassulaceae. It is a promising phytoremediation candidate accumulating substantial heavy metal ions without obvious signs of poisoning. However, few studies have focused on the regulatory roles of miRNAs and their targets in the hyperaccumulating ecotype of S. alfredii. Here, we combined analyses of the transcriptomics, sRNAs and the degradome to generate a comprehensive resource focused on identifying key regulatory miRNA-target circuits under Cd stress. A total of 87 721 unigenes and 356 miRNAs were identified by deep sequencing, and 79 miRNAs were differentially expressed under Cd stress. Furthermore, 754 target genes of 194 miRNAs were validated by degradome sequencing. A gene ontology (GO) enrichment analysis of differential miRNA targets revealed that auxin, redox-related secondary metabolism and metal transport pathways responded to Cd stress. An integrated analysis uncovered 39 pairs of miRNA targets that displayed negatively correlated expression profiles. Ten miRNA-target pairs also exhibited negative correlations according to a real-time quantitative PCR analysis. Moreover, a coexpression regulatory network was constructed based on profiles of differentially expressed genes. Two hub genes, ARF4 (auxin response factor 4) and AAP3 (amino acid permease 3), which might play central roles in the regulation of Cd-responsive genes, were uncovered. These results suggest that comprehensive analyses of the transcriptomics, sRNAs and the degradome provided a useful platform for investigating Cd hyperaccumulation in S. alfredii, and may provide new insights into the genetic engineering of phytoremediation.