Genomic prediction has been widely used in multiple areas and various genomic prediction methods have been developed. The majority of these methods, however, focus on statistical properties and ...ignore the abundant useful biological information like genome annotation or previously discovered causal variants. Therefore, to improve prediction performance, several methods have been developed to incorporate biological information into genomic prediction, mostly in single-trait analysis. A commonly used method to incorporate biological information is allocating molecular markers into different classes based on the biological information and assigning separate priors to molecular markers in different classes. It has been shown that such methods can achieve higher prediction accuracy than conventional methods in some circumstances. However, these methods mainly focus on single-trait analysis, and available priors of these methods are limited. Thus, in both single-trait and multiple-trait analysis, we propose the multi-class Bayesian Alphabet methods, in which multiple Bayesian Alphabet priors, including RR-BLUP, BayesA, BayesB, BayesCΠ, and Bayesian LASSO, can be used for markers allocated to different classes. The superior performance of the multi-class Bayesian Alphabet in genomic prediction is demonstrated using both real and simulated data. The software tool JWAS offers open-source routines to perform these analyses.
3D printing has become an essential part of bone tissue engineering and attracts great attention for the fabrication of bioactive scaffolds. Combining this rapid manufacturing technique with chemical ...precipitation, biodegradable 3D scaffold composed of polymer matrix (polylactic acid and polyethylene glycol), ceramics (nano hydroxyapatite), and drugs (dexamethasone (Dex)) is prepared. Results of water contact angle, differential scanning calorimeter, and mechanical tests confirm that incorporation of Dex leads to significantly improved wettability, higher crystallinity degree, and tunable degradation rates. In vitro experiment with mouse MC3T3‐E1 cells implies that Dex released from scaffolds is not beneficial for early cell proliferation, but it improves late alkaline phosphatase secretion and mineralization significantly. Anti‐inflammation assay of murine RAW 264.7 cells proves that Dex released from all the scaffolds successfully suppresses lipopolysaccharide induced interleukin‐6 and inducible nitric oxide synthase secretion by M1 macrophages. Further in vivo experiment on rat calvarial defects indicates that scaffolds containing Dex promote osteoinduction and osteogenic response and would be promising candidates for clinical applications.
Rapid fabrication technique fused deposition modeling is combined with chemical precipitation and extrusion technique to prepare composite polylactic acid/polyethylene glycol/nano hydroxyapatite/dexamethasone scaffold for application in bone regeneration. Anti‐inflammatory and immunosuppressive of dexamethasone is well preserved in the composite scaffold. This multifunctional 3D printing scaffold would be promising candidate for further clinical applications.
Polymeric micelle systems for drug delivery, monitor and chemotherapy have gained significant attention, and reductive polymeric micelle systems have become particularly attractive due to their ...controlled release behavior without additional assistance. However, there are challenges in accurately controlling drug and probe release from the nanoparticles and determining the loading content of drug and probe. To address these issues, we have developed a reduction-responsive Pt(IV) prodrug-based polymeric delivery system that can be dynamically monitored using aggregation-induced emission luminogens (AIE) based bioprobes. These polymeric micelle can self-assemble into nanoparticles and release both bio-active Pt(II) drug and bio-probe upon reduction activation. TPE molecules released in the inner endo/lysosomal microenvironment aggregate and fluoresce upon irradiation, thus allowing real-time tracking of drug biodistribution without additional contrast agents. Advantages of this system include position-specific chemical bond cleavage, control of platinum content, and monitoring of drug reduction and biodistribution.
Goji (fruits of Lycium barbarum L. and L. chinense Mill., Solanaceae) have been used as a traditional food and medicine for hundreds of years in Asian countries and are now consumed globally. Quality ...of herbal medicines is critical for safe use and has been shown to be affected by value chains.
Using a value chain (VC) framework, we aim at understanding the influence of different VC types on goji quality and revenue of stakeholders.
Participant observation and semi-structured interviews were conducted during five months of fieldwork in the main production areas in China with a total of 65 stakeholders. Quality of goji, behaviour and financial performance of stakeholders was documented and analysed for different VCs.
Ten different types of VCs were identified. VCs with vertical integration and horizontal collaboration were found to have a more coherent quality control and better goji quality as well as improved stakeholders’ financial performance. Vertical integration at different levels was found for independent farmer-based VCs, horizontal collaboration was found in the cooperative-based VCs. Full vertically integrated VCs were found in large-scale production.
Goji quality and stakeholders’ revenues are linked with different types of VCs which mirror stakeholders’ behaviour driven by target markets. Considering their positive influence on quality and revenues, well-developed vertically integrated value chains are likely to become more important in the near future.
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Bayesian regression methods that incorporate different mixture priors for marker effects are used in multi-trait genomic prediction. These methods can also be extended to genome-wide association ...studies (GWAS). In multiple-trait GWAS, incorporating the underlying causal structures among traits is essential for comprehensively understanding the relationship between genotypes and traits of interest. Therefore, we develop a GWAS methodology, SEM-Bayesian alphabet, which, by applying the structural equation model (SEM), can be used to incorporate causal structures into multi-trait Bayesian regression methods. SEM-Bayesian alphabet provides a more comprehensive understanding of the genotype-phenotype mapping than multi-trait GWAS by performing GWAS based on indirect, direct and overall marker effects. The superior performance of SEM-Bayesian alphabet was demonstrated by comparing its GWAS results with other similar multi-trait GWAS methods on real and simulated data. The software tool JWAS offers open-source routines to perform these analyses.
Although deep learning has been explored extensively for computer‐aided medical imaging diagnosis in human medicine, very little has been done in veterinary medicine. The goal of this retrospective, ...pilot project was to apply the deep learning artificial intelligence technique using thoracic radiographs for detection of canine left atrial enlargement and compare results with those of veterinary radiologist interpretations. Seven hundred ninety‐two right lateral radiographs from canine patients with thoracic radiographs and contemporaneous echocardiograms were used to train, validate, and test a convolutional neural network algorithm. The accuracy, sensitivity, and specificity for determination of left atrial enlargement were then compared with those of board‐certified veterinary radiologists as recorded on radiology reports. The accuracy, sensitivity, and specificity were 82.71%, 68.42%, and 87.09%, respectively, using an accuracy driven variant of the convolutional neural network algorithm and 79.01%, 73.68%, and 80.64%, respectively, using a sensitivity driven variant. By comparison, accuracy, sensitivity, and specificity achieved by board‐certified veterinary radiologists was 82.71%, 68.42%, and 87.09%, respectively. Although overall accuracy of the accuracy driven convolutional neural network algorithm and veterinary radiologists was identical, concordance between the two approaches was 85.19%. This study documents proof‐of‐concept for application of deep learning techniques for computer‐aided diagnosis in veterinary medicine.
Dense single nucleotide polymorphism (SNP) panels are widely used for genome-wide association studies (GWAS). In these panels, SNPs within a genomic segment tend to be highly correlated. Thus, ...association studies based on testing the significance of single SNPs are not very effective, and genomic-window based tests have been proposed to address this problem. However, when the SNP density on the genotype panel is not homogeneous, genomic-window based tests can lead to the detection of spurious associations by declaring effects of genomic windows that explain a large proportion of genetic variance as significant. We propose two methods to solve this problem.
To explore the expression differences of miRNA-21, miRNA-31 and miRNA-let7 between lung cancer patient and healthy people, thereby providing reference for early diagnosis of lung cancer.
Real-time ...PCR was employed to determine the expression difference between lung cancer patients (50 cases) and healthy people (24 cases). The clinical data of lung cancer patients were analyzed to explore the correlation between clinicopathological characteristics and expression level of miRNA-21, miRNA-31, miRNA-let7.
The relative expression levels of miRNA-21 and miRNA-31 in lung cancer group were obviously higher than those in healthy control group, and the relative expression level of miRNA-let7 in lung cancer group was slightly higher than that in healthy control group. Lung cancer patients with lymph node metastasis had higher expression level than those without lymph node metastasis. The ROC curve showed that the three miRNAs had clinical diagnosis efficiency for lung cancer, and the combined detection of the three miRNAs were more efficient in diagnosing lung cancer. Survival curve analysis suggested that the median survival times of patients in the miRNA-21 and miRNA-31 high expression groups were shorter than those in the low expression groups, and the median survival time of patients in miRNA-let7 high expression group was longer than that in the low expression group.
Plasma miRNA-21, miRNA-31 and miRNA-let7 may be diagnostic marker for lung cancer.
Theranostics of platinum (Pt)-based chemotherapy are able to self-track the biodistribution and pharmacokinetics while performing therapeutic effects. Pt-based CT imaging is expected to visualize and ...monitor the tumor throughout the entire tumor inhibition stage. However, a sufficient Pt concentration is necessary for CT imaging, which may bring about severe nephrotoxicity. A Bio-Pt-I compound is designed and synthesized by conjugation of iodine and biotin to the structure of Pt and further self-assembles into nanoparticles. The introduction of iodine not only enhances the CT imaging signal with a much lower dose of Pt but also overcomes the resistance of tumor cells to Pt-containing nanomedicine by inhibiting the expression of Bcl-2. Furthermore, biotin-mediated tumor targeting increases drug accumulation in tumors. This work combines CT imaging based self-track with efficient cisplatin-resistance reversion ability, which may promote the clinical transformation of Pt-containing nanomedicine.
Polyprodrug nanoparticles have been employed recently for safer and more effective cancer treatment. However, it remains a challenge to elucidate how and when the polyprodrug nanoparticles are ...dissociated and activated to release active drugs in cancer cells. Herein, a visible light-activatable Pt(IV) prodrug and an aggregation-induced emission luminogen (AIEgen) were copolymerized and embedded in the main chain of PtAIECP, and the chemotherapeutic doxorubicin (DOX) was subsequently encapsulated in the nanoparticles self-assembled by PtAIECP (PtAIECP@DOX NP). PtAIECP@DOX NP enabled the monitoring of both the light-activation of Pt(IV) prodrug to active Pt(II) and release of encapsulated DOX intracellularly through the fluorescence “turn-on” in the course of visible-light-induced polymer-main-chain cleavage and self-assembled structure dissociation in vitro and ex vivo. The synergistic anticancer efficacy of the activated Pt(II) drug and DOX in PtAIECP@DOX NP was also investigated in vitro and in vivo. The implementation of polyprodrug and AIE combination strategy empowered dual drug release and monitoring, which could be further used to guide the temporal and spatial control of light irradiation to maximize therapeutic efficiency, and will inspire other combinational bioimaging and therapy strategies.
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