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Doxycycline hydrochloride and florfenicol combination (DoxHcl&FF) is an effective treatment for respiratory diseases. In the study, our objective was to evaluate the activity of DoxHcl&FF against Actinobacillus pleuropneumoniae (APP) in porcine pulmonary epithelial lining fluid (PELF) and the optimal dosage scheme to avoid the development of resistance. The DoxHcl&FF was administered intramuscularly (IM) at 20 mg/kg, and the PELF was collected at different time points. The minimum inhibitory concentration (MIC) and time-mortality curves were also included in the study. Based on the sigmoid Emax equation and dose equations, the study integrated the in vivo pharmacokinetic data of infected pigs and ex vivo pharmacodynamic data to obtain the area under concentration time curve (AUC0-24h)/MIC values in PELF and achieve bacteriostatic activity, bactericidal activity and the virtual eradication of bacteria. The study showed that the combination of DoxHcl and FF caused no significant changes in PK parameters. The peak concentration (Cmax) of FF in healthy and diseased pigs was 8.87 ± 0.08 μg/mL and 8.67 ± 0.07 μg/mL, the AUC0-24h were 172.75 ± 2.52 h·μg/mL and 180.22 ± 3.13 h·μg/mL, the Cmax of DoxHcl was 7.91 ± 0.09 μg/mL and 7.99 ± 0.05 μg/mL, and the AUC0-24h was 129.96 ± 3.70 h·μg/mL and 169.82 ± 4.38 h·μg/mL. DoxHcl&FF showed strong concentration-dependent tendencies. The bacteriostatic, bactericidal, and elimination activity were calculated as 5.61, 18.83 and 32.68 h, and the doses were 1.37 (bacteriostatic), 4.59 (bactericidal) and 7.99 (elimination) mg/kg. These findings indicated that the calculated recommended dose could assist in achieving more precise administration, increasing the effectiveness of DoxHcl&FF treatment for APP infections.

The process optimization for the synthesis of an RSV antiviral agent is described. Key to the identification of these optimal conditions was the use of high-throughput experimentation to greatly re...

Contemporary DNN testing works are frequently conducted using metamorphic testing (MT). In general, de facto MT frameworks mutate DNN input images using semantics-preserving mutations and determine if DNNs can yield consistent predictions. Nevertheless, we find that DNNs may rely on erroneous decisions (certain components on the DNN inputs) to make predictions, which may still retain the outputs by chance. Such DNN defects would be neglected by existing MT frameworks. Erroneous decisions, however, would likely result in successive mis-predictions over diverse images that may exist in real-life scenarios. This research aims to unveil the pervasiveness of hidden DNN defects caused by incorrect DNN decisions (but retaining consistent DNN predictions). To do so, we tailor and optimize modern eXplainable AI (XAI) techniques to identify visual concepts that represent regions in an input image upon which the DNN makes predictions. Then, we extend existing MT-based DNN testing frameworks to check the consistency of DNN decisions made over a test input and its mutated inputs. Our evaluation shows that existing MT frameworks are oblivious to a considerable number of DNN defects caused by erroneous decisions. We conduct human evaluations to justify the validity of our findings and to elucidate their characteristics. Through the lens of DNN decision-based metamorphic relations, we re-examine the effectiveness of metamorphic transformations proposed by existing MT frameworks. We summarize lessons from this study, which can provide insights and guidelines for future DNN testing., The extended version of a paper to appear in the Proceedings of the 37th IEEE/ACM International Conference on Automated Software Engineering, 2022, (ASE '22), 13 pages

The transcription factor WRKY is widespread in the plant kingdom and plays a crucial role in diverse abiotic stress responses in plant species. Tritipyrum, an octoploid derived from an intergeneric cross between Triticum aestivum (AABBDD) and Thinopyrum elongatum (EE), is a valuable germplasm resource for introducing superior traits of Th. elongatum into T. aestivum. The recent release of the complete genome sequences of T. aestivum and Th. elongatum enabled us to investigate the organization and expression profiling of Tritipyrum WRKY genes across the entire genome.In this study, 346 WRKY genes, from TtWRKY1 to TtWRKY346, were identified in Tritipyrum. The phylogenetic analysis grouped these genes into three subfamilies (I-III), and members of the same subfamilies shared a conserved motif composition. The 346 TtWRKY genes were dispersed unevenly across 28 chromosomes, with 218 duplicates. Analysis of synteny suggests that the WRKY gene family may have a common ancestor. Expression profiles derived from transcriptome data and qPCR demonstrated that 54 TtWRKY genes exhibited relatively high levels of expression across various salt stresses and recovery treatments. Tel1E01T143800 (TtWRKY256) is extremely sensitive to salt stress and is on the same evolutionary branch as the salt-tolerant A. thaliana genes AtWRKY25 and AtWRKY33. From 'Y1805', the novel AtWRKY25 was cloned. The Pearson correlation analysis identified 181 genes that were positively correlated (R0.9) with the expression of TtWRKY256, and these genes were mainly enriched in metabolic processes, cellular processes, response to stimulus, biological regulation, and regulation of biological. Subcellular localization and qRT-PCR analysis revealed that TtWRKY256 was located in the nucleus and was highly expressed in roots, stems, and leaves under salt stress.The above results suggest that TtWRKY256 may be associated with salt stress tolerance in plants and may be a valuable alien gene for improving salt tolerance in wheat.

Correction for ‘Recent development of gene therapy for pancreatic cancer using non-viral nanovectors’ by Yu Liu et al., Biomater. Sci., 2021, DOI: 10.1039/d1bm00748c.

Pancreatic cancer (PC), characterized by its dense desmoplastic stroma and hypovascularity, is one of the most lethal cancers with a poor prognosis in the world. Traditional treatments such as chemotherapy, radiotherapy, and targeted therapy show little benefit in the survival rate in patients with advanced PC due to the poor penetration and resistance of drugs, low radiosensitivity, or severe side effects. Gene therapy can modify the morbific and drug-resistant genes as well as insert the tumor-suppressing genes, which has been shown to have great potential in PC treatment. The development of safe non-viral vectors for the highly efficient delivery of nucleic acids is essential for effective gene therapy, and has been attracting much attention. In this review, we first summarized the PC-promoting genes and gene therapies using plasmid DNA, mRNA, miRNA/siRNA-based RNA interference technology, and genome editing technology. Second, the commonly used non-viral nanovector and theranostic gene delivery nanosystem, especially the tumor microenvironment-sensitive delivery nanosystem and the cell/tumor-penetrating delivery nanosystem, were introduced. Third, a combination of non-viral nanovector-based gene therapy and other therapies, such as immunotherapy, chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT), for PDAC treatment was discussed. Finally, a number of clinical trials have demonstrated the proof-of-principle that gene therapy or the combination of gene therapy and chemotherapy using non-viral vectors can inhibit the progression of PC. Although most of the non-viral vector-based gene therapies and their combination therapy are still under preclinical research, the development of genetics, molecular biology, and novel vectors would promote the clinical transformation of gene therapy.

Powdery mildew is one of the most devastating foliar diseases in wheat production. The wild relative

The present work focuses on the existence of chimera states in two-layer networks of locally, nonlocally, and globally coupled Hindmarsh–Rose neurons. We show that chimera states occur in all three coupled neuronal networks by changing synaptic coupling strength and the number of coupled neighbors, and traveling chimera state exists in networks by using local and nonlocal couplings. Particularly, we find that in the nonlocally coupled network, there exist regions of coherent state, which can produce a wave such that the period becomes longer with the increase of the number of coupled neighbors. Interestingly, we observe a new chimera state with the coexistence of interlayer synchronous and asynchronous chimera states, which we named as the interlayer semi-synchronous chimera state. In addition, the results indicate that the interaction between layers in neuronal networks can induce different types of chimera states and firing patterns, which could be useful to control neural firing patterns and deepen the understanding of neuronal evolution where coherent and incoherent dynamics coexist.

Cronobacter sakazakii is an important opportunistic food-borne pathogen, and it can cause severe diseases with main symptoms including neonatal meningitis, necrotizing enterocolitis, and sepsis. For the achievement of practical and convenient detection of viable C. sakazakii, a simple and robust strategy based on the cascade signal amplification of RT-PCR triggered G-quadruplex DNAzyme catalyzed reaction was firstly used to develop an effective and sensitive DNAzyme electrochemical assay. Without viable C. sakazakii in the samples there are no RT-PCR and DNAzyme products, which can cause a weak electrochemical response. Once viable C. sakazakii exists in the samples, an obvious enhancement of the electrochemical response can be achieved after the target signal is amplified by RT-PCR and the resulting DNAzyme, which catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 with the assistance of the cofactor hemin. Our novel assay can be performed in a range of 2.4 × 107 CFU mL-1 to 3.84 × 104 CFU mL-1 (R2 = 0.9863), with a detection limit of 5.01 × 102 CFU mL-1. Through the assay of 15 real samples, electrochemical detection assay provided the same results as conventional detection methods. Therefore, detection of viable C. sakazakii based on G-quadruplex DNAzyme electrochemical assay with RT-PCR demonstrates the significant advantages of high sensitivity, low cost and simple manipulation over existing approaches and offers an opportunity for potential application in pathogen detection.

The prosperous trend of deploying deep neural network (DNN) models to diverse hardware platforms has boosted the development of deep learning (DL) compilers. DL compilers take the high-level DNN model specifications as input and generate optimized DNN executables for diverse hardware architectures like CPUs, GPUs, and various hardware accelerators. Compiling DNN models into high-efficiency executables is not easy: the compilation procedure often involves converting high-level model specifications into several different intermediate representations (IR), e.g., graph IR and operator IR, and performing rule-based or learning-based optimizations from both platform-independent and platform-dependent perspectives. Despite the prosperous adoption of DL compilers in real-world scenarios, principled and systematic understanding toward the correctness of DL compilers does not yet exist. To fill this critical gap, this paper introduces MT-DLComp, a metamorphic testing framework specifically designed for DL compilers to effectively uncover erroneous compilations. Our approach leverages deliberately-designed metamorphic relations (MRs) to launch semantics-preserving mutations toward DNN models to generate their variants. This way, DL compilers can be automatically examined for compilation correctness utilizing DNN models and their variants without requiring manual intervention. We also develop a set of practical techniques to realize an effective workflow and localize identified error-revealing inputs. Real-world DL compilers exhibit a high level of engineering quality. Nevertheless, we detected over 435 inputs that can result in erroneous compilations in four popular DL compilers, all of which are industry-strength products maintained by Amazon, Facebook, Microsoft, and Google. While the discovered error-triggering inputs do not cause the DL compilers to crash directly, they can lead to the generation of incorrect DNN executables. With substantial manual effort and help from the DL compiler developers, we uncovered four bugs in these DL compilers by debugging them using the error-triggering inputs. Our proposed testing frameworks and findings can be used to guide developers in their efforts to improve DL compilers.

For early detection and diagnosis of gastric cancer, a novel, highly sensitive detection of microRNA-378 was developed through rolling circle amplification and DNA-templated silver nanoclusters as a lable-free fluorescent probe. DNA-templated fluorescent silver nanoclusters (DNA/AgNCs) to make target signal cascade amplification were prepared and identified through their fluorescent spectrum. MiRNA-378 trigged rolling circle amplification to obtain the complementary sequence (cDNA) to combine with two DNA/AgNCs in the middle of a sandwich structure to induce the new fluorescent signal at a new wavelength. In the presence of microRNA-378, a large amount of RCA product cDNAs were hybridized with DNA/AgNCs as the fluorescence nanocluster beacon, resulting in fluorescence enhanced “turn-on” phenomenon. This study indicated that amplified fluorescence detection of microRNA-378 is a stable, low-cost, highly specific, and ultra-low as 1.07 fM detectability. The proposed approach of signal synergetic amplification facilitating the fluorescence detection microRNA shows great potential for potentially clinically diagnosis.

As most of intracellular reactive oxygen species (ROS) is produced in the mitochondria, mitochondrial modulation of cancer cell is a promising strategy for maximizing the in situ-activable combination therapy of oxidative catastrophe and cascaded chemotherapy. Herein, a serum-stable polymer‑calcium phosphate (CaP) hybrid nanocapsule carrying siRNA against ADP-ribosylation factor 6 (Arf6) overexpressed in cancer cells and parent drug camptothecin (CPT), designated as PTkCPT/siRNA, was developed for the RNAi-induced oxidative catastrophe and cascaded chemotherapy. A copolymer of mPEG-P(Asp-co-TkCPT), covalently tethered with chemotherapeutic CPT via a ROS-labile dithioketal (Tk) linker, was synthesized and self-assembled into a PTkCPT micelle as a nanotemplate for the CaP mineralization. The as-prepared PTkCPT/siRNA nanoparticle showed a core-shell-distinct nanocapsule which was consisted of a spherical polymeric core enclosed within a CaP shell capable of releasing siRNA in response to lysosomal acidity. Blocking Arf6 signal pathway of cancer cells led to their mitochondrial aggregation and subsequently induced a burst of ROS for oxidative catastrophe, which further triggered the cascaded CPT chemotherapy via the breakage of ROS-labile dithioketal linker. This strategy of RNAi-induced oxidative catastrophe and cascaded chemotherapy resulted in a significant combination effect on cancer cell killing and tumor growth inhibition in mice with low side effects, and provided a promising paradigm for precise cancer therapy.

In vitro propagation technology with plant growth regulators (PGRs) is generally applied in the cultivation of Scabiosa tschiliensis, which can solve collection difficulties and limited resources of S. tschiliensis. Nevertheless, comprehensive metabolomic evaluation on S. tschiliensis with PGR effects is still lacking. In this work, a non-targeted metabolomics approach, coupled with statistical and pathway enrichment analysis, was used to assess the regulatory influences of 6-benzylaminopurine (6-BA) and kinetin (KT) applied in S. tschiliensis. The results showed that the PGRs affect metabolism differentially, and the addition of 6-BA and KT can increase different secondary metabolites. In the two PGR groups, some primary metabolites such as L-phenylalanine, L-tyrosine, L-arginine, L-asparagine, and D-proline were significantly reduced. We suspect that under the action of PGRs, these decreased amino acids are derived into secondary metabolites such as umbelliferone, chlorogenic acid, and glutathione. Additionally, some of those secondary metabolites have a biological activity and can also promote the plant growth. Our results provide a basis for the targeted cultivation and utilization of S. tschiliensis, especially the expression of metabolites related to PGR application.

Visual question answering (VQA) takes an image and a natural-language question as input and returns a natural-language answer. To date, VQA models are primarily assessed by their accuracy on high-level reasoning questions. Nevertheless, Given that perception tasks (e.g., recognizing objects) are the building blocks in the compositional process required by high-level reasoning, there is a demanding need to gain insights into how much of a problem low-level perception is. Inspired by the principles of software metamorphic testing, we introduce MetaVQA, a model-agnostic framework for benchmarking perception capability of VQA models. Given an image i, MetaVQA is able to synthesize a low-level perception question q. It then jointly transforms (i, q) to one or a set of sub-questions and sub-images. MetaVQA checks whether the answer to (i, q) satisfies metamorphic relationships (MRs), denoting perception consistency, with the composed answers of transformed questions and images. Violating MRs denotes a failure of answering perception questions. MetaVQA successfully detects over 4.9 million perception failures made by popular VQA models with metamorphic testing. The state-of-the-art VQA models (e.g., the champion of VQA 2020 Challenge) suffer from perception consistency problems. In contrast, the Oscar VQA models, by using anchor points to align questions and images, show generally better consistency in perception tasks. We hope MetaVQA will revitalize interest in enhancing the low-level perceptual abilities of VQA models, a cornerstone of high-level reasoning.

In vitro propagation technology with plant growth regulators (PGRs) is generally applied in the cultivation of Scabiosa tschiliensis, which can solve collection difficulties and limited resources of S. tschiliensis. Nevertheless, comprehensive metabolomic evaluation on S. tschiliensis with PGR effects is still lacking. In this work, a non-targeted metabolomics approach, coupled with statistical and pathway enrichment analysis, was used to assess the regulatory influences of 6-benzylaminopurine (6-BA) and kinetin (KT) applied in S. tschiliensis. The results showed that the PGRs affect metabolism differentially, and the addition of 6-BA and KT can increase different secondary metabolites. In the two PGR groups, some primary metabolites such as L-phenylalanine, L-tyrosine, L-arginine, L-asparagine, and D-proline were significantly reduced. We suspect that under the action of PGRs, these decreased amino acids are derived into secondary metabolites such as umbelliferone, chlorogenic acid, and glutathione. Additionally, some of those secondary metabolites have a biological activity and can also promote the plant growth. Our results provide a basis for the targeted cultivation and utilization of S. tschiliensis, especially the expression of metabolites related to PGR application.

Theranostic nanosystem has been demonstrated great potential in real-timely monitoring drug biodistribution and therapeutic response. It is still a challenge to fabricate a theranostic nanosystem that possesses the properties of good biocompatibility, a high magnetic resonance imaging (MRI) sensitivity, and stimuli-responsive drug release for the diagnosis and treatment of hepatocellular carcinoma. Here, a pH-responsive micelle, which was self-assembled from biodegradable poly(amino acid) block copolymer mPEG-PAsp(DIP)-co-PLLeu, was constructed to load both chemotherapeutic paclitaxel (PTX) and MRI contrast agent superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs/PTX-coloaded PDPL micelle (SPIONs/PTX-PDPL) had a hydrodynamic particle size of 134.5 ± 11.2 nm. The theranostic SPIONs/PTX-PDPL not only effectively delivered PTX and SPION into Bel-7402 cancer cells but also rapidly released PTX in acidic lysosome to induce cell apoptosis. Meanwhile, in vitro MR imaging sensitively detected the liver cancer cells after co-incubation with SPIONs/PTX-PDPL micelle. The SPIONs/PTX-PDPL micelle is a potential theranostic nanosystem in terms of the simultaneous chemotherapy and MR imaging of hepatocellular carcinoma.

MicroRNA-378 (miRNA-378) is widely regarded as a novel noninvasive serum biomarker for early detection of gastric cancer. In the current study, a T4 DNA ligase-mediated circular template specific to target and a target-triggering rolling circle amplification (RCA) strategy was proposed for gastric cancer biomarker miRNA-378 visual detection. After multiple signal amplification through RCA and DNAzyme, a simple method for colorimetric detection of miRNA-378 was first developed with an ultralow detection limit of 80 fM per reaction by the naked eye, and synergetic signal cascade amplification enables the assay to have extraordinarily high sensitivity and the potential for clinical diagnosis.

Interference-free determination of polycyclic aromatic hydrocarbons (PAHs) in water pollution is proposed based on third-order correction algorithms with quadrilinear component modeling applied to the constructed four way fluorescence excitation–emission-sample data array with higher accuracy and better predictive ability than second-order (three-dimension) correction. Alternating weighted residue constraint quadrilinear decomposition (AWRCQLD), quadrilinear parallel factor analysis (4-PARAFAC), alternate penalty quadrilinear decomposition (APQLD) and alternate penalty trilinear decomposition (APTLD) are applied to acenaphthene (ANA), naphthalene (NAP) and fluorene (FLU) respectively. Fulvic acid affects PAHs determination seriously in real-world situation, so it is simulated as an interfering agent. Excitation-emission fluorescence matrixes (EEMs) of PAHs are measured at different volumes of fulvic acid simulated different interference conditions, to construct a four-way data array. After the four-way spectra data is analyzed by AWRCQLD, 4-PARAFAC, and APQLD, three-way EEMs analyzed by APTLD, results show that, on the one hand, PAHs can be measured more accurately with four-way data combined with third-order calibration than lower-order. On the other hand, AWRCQLD algorithm can reflect the superiority of third-order advantage better with higher recovery rate and smaller root mean square error, than other third-order or second-order correction algorithms.

The Staphylococcus aureus (S. aureus) cow mastitis causes great losses to the cow industry. In order to improve the treatment effect of tilmicosin against cow mastitis, the combination of solid lipid nanoparticle (SLN) technology with in situ hydrogel technology was used to prepare the self-assembly tilmicosin nanogel (TIL-nanogel). The physicochemical characteristics, in vitro release, antibacterial activity and in vivo treatment efficacy of TIL-SLNs and TIL-nanogel were studied, respectively. The results showed the loading capacity (LC), encapsulation efficiency (EE), size, zeta potential and poly dispersion index (PDI) of TIL-nanogel were 23.33 ± 0.77%, 67.89 ± 3.01%, 431.57 ± 12.87 nm, 8.3 ± 0.06 mv and, 0.424 ± 0.032, respectively. The TIL-nanogel showed stronger sustained release in vitro than TIL-SLNs and commercial injection. The cure rate of half dosage and normal dosage of TIL-nanogel was 58.3% and 75.0%, which was higher than that of commercial injection (50.0%) at normal dosage. The results suggest that the treatment dosage of tilmicosin for cow mastitis could be reduced by TIL-nanogel. The novel TIL-nanogel will be beneficial by decreasing the usage of tilmicosin and the treatment costs of cow mastitis.

Kinsenoside is a characteristic component of Anoectochilus roxburghii and accounts for this herb's medicinal and edible values. No international certified standard method is available for kinsenoside analysis as well as extraction and preservation.To develop a more accurate analytical method of kinsenoside. The effects of extraction and drying methods of A. roxburghii on kinsenoside efficiency were investigated for the first time, as well as to examine the kinsenoside stability.The amino (NHAn accurate method of kinsenoside detection by HPLC-ELSD with dual columns of NHThis study provides a reliable experimental method and theoretical basis for the quality control of kinsenoside from A. roxburghii, as well as other glycosides.

Wheat is one of the most important staple food crops in many parts of the world. Nitrogen (N) is often considered to be the most important mineral nutrient element for crop growth and development. Nitrogen use efficiency (NUE) comprises nitrogen uptake efficiency (NUpE) and nitrogen utilization efficiency (NUtE). We constructed a high-density genetic map using a set of 184 recombinant inbred lines (RILs) derived from the cross ‘Tainong 18 × Linmai 6’ (TL-RILs). In this study, 14 seedling traits and 17 maturity traits related to NUE and agronomic traits of wheat were investigated using the TL-RILs under hydroponic culture trials with high N (HN), moderate N (MN) and low N (LN) levels in two time frames, and under field trials with HN and LN levels in two growing seasons. A total of 121 and 130 quantitative trait loci (QTLs) we detected at seedling and maturity stages, respectively. Of these, 47 relatively high-frequency QTLs (RHF-QTLs) and 16 QTL clusters were found. The most important cluster, C9, included morphological, biomass, yield, NUpE and NUtE traits at the same time. The contributions for most QTLs were high, with the highest contribution of 30.00%. Seventeen RHF-QTLs were detected in this cluster, and it showed a favorable relationship between the RHF-QTLs for breeding programs. The markers in the region of cluster C9 should be valuable in marker-assisted selection (MAS). The sequence of DArT marker D-3940950 in the C9 region was identified to the RhtB1 gene with the similarity of 100% by BLAST against the Chinese Spring genome (IWGSCv1.0). The correlation analysis suggested that the morphological/biomass traits and eight yield traits can be considered as the primary morphological indexes for the evaluation of NUE instead of using element determinations, and the outcomes make it easy to identify NUE on a large scale.

Cronobacter sakazakii is a typical food-borne bacterium that causes clinical symptoms including necrotizing enterocolitis, bacteremia, and meningitis with a mortality rate of 40 %–80 %. In this study, a pair of split G-rich DNA probes was assembled into the DNAzyme capable of mimicking peroxidase. The assembly was utilized to provide a simple, low-cost, highly specific, and sensitive method for rapid detection of viable C. sakazakii. In the absence of viable C. sakazakii, the two split G-rich DNA probes formed DNAzyme, mimicked the activity of peroxidase and displayed colorimetric signals to indicate detection results. In the presence of viable C. sakazakii, specific recognition by the aptamer results in the destruction of the DNAzyme-aptamer complex, and subsequently the colorimetric signal is “turned-off” due to the decrease in DNAzyme bioactivity. Under the optimal reaction conditions, there is a linear relationship between absorption intensity at 418 nm and logarithmic concentration of C. sakazakii in the range of 2–1200 CFU/mL (R2 = 0.9839), with a detection limit of 1.2 CFU/mL. This is the highest sensitivity ever reported for viable C. sakazakii detection. Artificially contaminated samples were assayed by this novel sensor, and numerous advantages were discovered, including ultra-low sensitivity, low-cost, simple operation, and good performance, compared to existing methods. We believe the DNAzyme shows great potential for food safety applications.

The potentiality of PGPR and biocontrol bacteria in agriculture is steadily increased as it offers an attractive way to replace the use of chemical fertilizers, pesticides and other supplements. This study aimed to investigate the effects and potential mechanism of inoculation with two Bacillus velezensis strains on the growth and quality improvement of Anoectochilus roxburghii (Wall.) Lindl. (MRH) and Anoectochilus formosanus (Wall.) Lindl. (YYB). The control treatment was non-inoculated (CK) and the coculture treatments were inoculated with Bacillus velezensis D2WM (D2), Bacillus velezensis ZJ-11 (ZJ-11), Bacillus velezensis D2WM and Bacillus velezensis ZJ-11 (D2+ZJ-11). The fresh weight, plant length, amount of active compounds, as well as chlorophyll content were significantly increased under D2, ZJ-11, and D2+ZJ-11 treatments compared with MRH and YYB plants in CK. In particular, D2+ZJ-11 treatment resulted in the greatest growth promotion. In MRH and YYB plants, the fresh weight increased by 82.6 % and 106.6 %, the kinsenoside content increased by 9.33 % and 21.65 % per gram, and the flavonoid content increased by 44.70 % and 21.07 % per gram, respectively. D2WM and ZJ-11 were capable of secreting siderophore, phytase, indole-3-acetic acid (IAA), and zeatin to promote plant nutrient assimilation and growth. Moreover, when D2WM and ZJ-11 were both inoculated with Anoectochilus roxburghii, the rhizosphere soil enzyme activities of urease, phosphatase, and invertase were significantly higher than control, thus helped to provide more nutrients to Anoectochilus. Further, the analysis of microbial community diversity indicated the increase of abundance of beneficial microorganisms, such as nitrogen-fixing bacteria, Basidiomycota and Ascomycota both of which are known to fuel their plant partners with mineral nutrients from the soil. Additionally, the abundance of pathogens belonging to Xanthobacteraceae as well as Cladophialophora and Penicillium were reduced. Hence, coculture with beneficial microorganisms can improve the growth and quality of Anoectochilus plants via promoting nutrient assimilation and regulating rhizosphere microbial community. This technique is of great application value in promoting the efficient cultivation and production of high-quality plant materials.

Additional file 3. Partial nucleotide sequence of Gb_11937. The nucleotide sequence of Gb_11937 encoded R2 and R3 of AP2 domain were completely identical. The red characters encoded the R2 and R3 repeat of AP2 domain, the yellow ones were also completely identical, indicating a duplication.

Additional file 2. Sequence alignment of all B3 ERFs. Arabidopsis B3 ERF were obtained from TAIR ( https://www.arabidopsis.org/ ), while CrORCA3 downloaded from UniprotKB under accession number Q9LDB6. This CrORCA3, lacked of the EDLL-motif, was certificated to up-regulate biosynthesis of terpenoid indole alkaloids in Catharanthus roseus.

Combined photothermo-chemotherapy is a new cancer treatment modality that improves therapeutic outcome by synergistic actions of two different means. A reduction and pH dual sensitive polymeric vesicle encapsulating doxorubicin (DOX) was prepared and then decorated with a gold layer using a modified method of in situ gold seed growth. By tuning the compactness of gold layer, the gold nanoshell may possess a desirable light absorption peak for tumor photothermal therapy using near-infrared (NIR) laser irradiation, a method featuring high tissue penetrability essential for in vivo applications. The NIR light energy was converted into heat, which killed cancer cells in the vicinity and induced the rupture of nanoshell to release DOX inside tumor. Therefore, a combined photothermo-chemotherapy of tumor can be achieved precisely at tumor site. In addition, DOX released in the thermochemotherapeutic mode effectively penetrated tumor tissue, which is meaningful considering the intrinsic low tissue penetrability of nanomedicines. In nude mice bearing human Bel-7402 hepatoma, the photothermo-chemotherapy using DOX-loaded gold nanoshell appeared advantageous over a chemotherapy or a photothermal therapy alone.

The gene silencing activity of small interfering RNA (siRNA) has led to their use as tools for target validation and as potential therapeutics for a variety of diseases. A major challenge is the development of vectors with high delivery efficiency and low toxicity. Although poly(ethylenimine) (PEI) has been regarded as the most promising polymeric vector for nucleic acid delivery, the nonbiodegradable structure greatly hinders its clinical application. In the present study, a diblock copolymer, PEG-PAsp(DIP-DETA), of poly(ethylene glycol) (PEG) and poly(L-aspartic acid) (PAsp) randomly grafted with pH-sensitive 2-(diisopropylamino)ethylamine (DIP) and diethylenetriamine (DETA) groups was synthesized via ring-opening polymerization and aminolysis reaction. Similar to polyethylenimine (PEI), the copolymer possesses a multiamine structure that not only allows effective siRNA complexation at neutral pH but also facilitates lysosomal release of siRNA via a proton buffering effect. Moreover, the poly(L-aspartic acid) backbone renders the vector biodegradability, which is not achievable with PEI. This novel polymeric vector can mediate effective intracellular siRNA delivery in various cancer cells. Consequently, the delivery of BCL-2 siRNA resulted in target gene silencing, inducing apoptosis and inhibiting the growth of cancer cells. These results show the potential of this non-PEI based polymeric vector with proton buffering capacity and biodegradability for siRNA delivery in cancer therapy.

Supplementary Figures. This is a pdf file. This file includes 2 supplementary figures. (PDF 1148 kb)

Background Recent results demonstrated that either non-coding or coding genes generate phased secondary small interfering RNAs (phasiRNAs) guided by specific miRNAs. Till now, there is no studies for phasiRNAs in Panax notoginseng (Burk.) F.H. Chen (P. notoginseng), an important traditional Chinese herbal medicinal plant species. Methods Here we performed a genome-wide discovery of phasiRNAs and its host PHAS loci in P. notoginseng by analyzing small RNA sequencing profiles. Degradome sequencing profile was used to identify the trigger miRNAs of these phasiRNAs and potential targets of phasiRNAs. We also used RLM 5’-RACE to validate some of the identified phasiRNA targets. Results After analyzing 24 small RNA sequencing profiles of P. notoginseng, 204 and 90 PHAS loci that encoded 21 and 24 nucleotide (nt) phasiRNAs, respectively, were identified. Furthermore, we found that phasiRNAs produced from some pentatricopeptide repeat-contain (PPR) genes target another layer of PPR genes as validated by both the degradome sequencing profile and RLM 5’-RACE analysis. We also found that miR171 with 21 nt triggers the generations of 21 nt phasiRNAs from its conserved targets. Conclusions We validated that some phasiRNAs generated from PPRs and TASL genes are functional by targeting other PPRs in trans. These results provide the first set of PHAS loci and phasiRNAs in P. notoginseng, and enhance our understanding of PHAS in plants. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-4331-0) contains supplementary material, which is available to authorized users.

A novel surface-plasmon-enhanced structure is proposed to improve the absorption efficiency of organic solar cells in this paper. The PEDOT:PSS-Ag light-trapping structure introduced allows light to be reflected multiple times between the multilayer films, increasing the optical path length of light in the device and the light absorption by the absorption layer. The Ag film in P3HT:PCBM absorption layer can induce surface plasmons, which can enhance the electromagnetic energy around Ag film, improving the light absorption ability of organic solar cells. Based on the finite element method, the COMSOL-RF module is used to simulate the designed structure, and the absorption efficiency, electric field mode distribution and total power loss density distribution at different structural parameters were obtained. The results reveal that the absorption efficiency is more than 80% in the wavelength range of 485 nm to 520 nm in TE mode and more than 85% in the wavelength range of 495 nm to 595 nm in TM mode, providing a reliable basis for the development of high-performance organic solar cells.

A novel reduction and pH dual-sensitive nonviral vector for long-circulating and tumor-targeted siRNA delivery is described. The nanomedicine is negatively charged at neutral pH of bloodstream whereas it is positively charged at lower pH of tumor tissue (ca. 6.8). Interlayer crosslinking with disulfide bonds stabilizes the nanomedicine during blood circulation and allows quick intracellular siRNA release after endocytosis.

The diblock copolymer (PEI-PAsp(DIP/MEA)) of branched polyethyleneimine (PEI) and biodegradable poly(2-diisopropylamino/2-mercaptoethylamine) ethyl aspartate (PAsp(DIP/MEA)) was synthesized and assembled into nanovesicles for the co-delivery of cytosine deaminase (CD) gene and 5-fluorocytosine (pCMVCD/5-FC) into glioma cells. The nanovesicle comprises a hydrophilic outerlayer of branched PEI for pCMVCD complexation, a hydrophilic inner cavity for prodrug 5-FC loading, and a pH-sensitive membrane crosslinked by disulfide to prevent drug leakage into the bloodstream-simulating environment with neutral pH and without reducing agent. Yet, once the PPDM (PEI-PAsp(DIP/MEA)) nanovesicle was internalized into cancer cells and entrapped inside lysosomes featuring a low pH (∼5) and enriched reducing agent (∼10 mM GSH), it dissociated as a result of tertiary amine protonation and disulfide bond breakage to release the loaded drug. The in vitro release studies showed that less than 10% of 5-FC was released from the nanovesicle in 24 h at pH 7.4, whereas about 98% of 5-FC was released in the presence of 10 mM GSH at pH 5.0. The prodrug 5-FC was converted into its toxic active metabolite 5-fluorouracil (5-FU) by cytosine deaminase inside C6 glioma cells, owing to the effective CD gene transfection and expression. As a result, the 5-FC/pCMVCD-loaded nanovesicle induced effective apoptosis and generated a significant cytotoxic effect in the cancer cells. Our results indicated that this multifunctional nanovesicle is a promising carrier for the co-delivery of gene and drug or prodrug in cancer therapy.

Catalytic activity of rare-earth metal complexes for dehydrocoupling of Me2NH center dot BH3 is deeply ligand- and metal ion-dependent, and 1-methyl boratabenzene yttrium alkyl shows very high activity for the reaction (TOF > 1000 h(-1)). The transformati

The hydroboration of alkenes, alkynes, imines, and carbodiimides using the anionic 1-H-boratabenzene ligand bound to rare-earth (RE = Y, Lu), transition (Zr and Rh), and main-group (Li) metals is reported. This hydroboration is metal ion dependent; in the case of 1-H-boratabenzene transition metal complexes, the reactivity follows the trend RE > Zr > Rh. Hydroboration with 1-H-boratabenzene rare-earth metal complexes works well for a range of unsaturated substrates, including 1-hexene, allyl propyl ether, allyl ether, 3-hexyne, benzylidene-n-propylamine, and N,N′-diisopropylcarbodiimide, thus generating a series of new alkyl-, alkenyl-, amino-, or amidino-functionalized boratabenzene rare-earth metal complexes in high yields. The reactions are highly anti-Markovnikov selective, and the mechanism has been investigated by deuterium-labeling experiments. In comparison, a 1-H-boratabenzene Zr complex reacts with benzylidene-n-propylamine and N,N′-diisopropylcarbodiimide, and a 1-H-boratabenzene Rh complex rea...

Drug resistance is the greatest challenge in clinical cancer chemotherapy. Co-delivery of chemotherapeutic drugs and siRNA to tumor cells is a vital means to silence drug resistant genes during the course of cancer chemotherapy for an improved chemotherapeutic effect. This study aims at effective co-delivery of siRNA and anticancer drugs to tumor cells. A ternary block copolymer PEG-PAsp(AED)-PDPA consisting of pH-sensitive poly(2-(diisopropyl amino)ethyl methacrylate) (PDPA), reduction-sensitive poly(N-(2,2'-dithiobis(ethylamine)) aspartamide) PAsp(AED), and poly(ethylene glycol) (PEG) is synthesized and assembled into a core-shell structural micelle which encapsulated doxorubicin (DOX) in its pH-sensitive core and the siRNA-targeting anti-apoptosis BCL-2 gene (BCL-2 siRNA) in a reduction-sensitive interlayer. At the optimized size and zeta potential, the nanocarriers loaded with DOX and BCL-2 siRNA may effectively accumulate in the tumor site via blood circulation. Moreover, the dual stimuli-responsive design of micellar carriers allows microenviroment-specific rapid release of both DOX and BCL-2 siRNA inside acidic lysosomes with enriched reducing agent, glutathione (GSH, up to 10 mM). Consequently, the expression of anti-apoptotic BCL-2 protein induced by DOX treatment is significantly down-regulated, which results in synergistically enhanced apoptosis of human ovarian cancer SKOV-3 cells and thus dramatically inhibited tumor growth.

With the development of mobile Internet, more and more people begin to get convenient service by mobile phones. Obtaining one's current location by GPS positioning or network positioning has become one of the important foundations in most applications of location based service. In this paper, we designed and implemented a personalized positioning and navigation system based on the Android platform. With the combination of GPS positioning and network positioning, and using Google Map API, this system provides the following functions: view the current location, get the navigation route, address query and view historical location records. Keywords-location; navigation; Android; Google Map