Climate as a Predictive Factor for Invasion: Unravelling the Range Dynamics of Carpomya vesuviana Costa.

Invasive alien species (IAS) significantly affect global native biodiversity, agriculture, industry, and human health. Carpomya vesuviana Costa, 1854 (Diptera: Tephritidae), a significant global IAS, affects various date species, leading to substantial economic losses and adverse effects on human health and the environment. This study employed biomod2 ensemble models, multivariate environmental similarity surface and most dissimilar variable analyses, and ecological niche dynamics based on environmental and species data to predict the potential distribution of C. vesuviana and explore the environmental variables affecting observed patterns and impacts. Compared to native ranges, ecological niche shifts at invaded sites increased the invasion risk of C. vesuviana globally. The potential geographical distribution was primarily in Asia, Africa, and Australia, with a gradual increase in suitability with time and radiation levels. The potential geographic distribution centre of C. vesuviana is likely to shift poleward between the present and the 2090s. We also show that precipitation is a key factor influencing the likely future distribution of this species. In conclusion, climate change has facilitated the expansion of the geographic range and ecological niche of C. vesuviana, requiring effective transnational management strategies to mitigate its impacts on the natural environment and public health during the Anthropocene. This study aims to assess the potential threat of C. vesuviana to date palms globally through quantitative analytical methods. By modelling and analysing its potential geographic distribution, ecological niche, and environmental similarities, this paper predicts the pest's dispersal potential and possible transfer trends in geographic centres of mass in order to provide prevention and control strategies for the global date palm industry.

A new chromosome-scale genome of wild Brassica oleracea provides insights into the domestication of Brassica crops.

The cultivated diploid Brassica oleracea is an important vegetable crop, but the genetic basis of its domestication remains largely unclear in the absence of high-quality reference genomes of wild B. oleracea. Here, we report the first chromosome-level assembly of the wild Brassica oleracea L. W03 genome (total genome size, 630.7 Mb; scaffold N50, 64.6 Mb). Using the newly assembled W03 genome, we constructed a gene-based B. oleracea pangenome and identified 29 744 core genes, 23 306 dispensable genes, and 1896 private genes. We re-sequenced 53 accessions, representing six potential wild B. oleracea progenitor species. The results of the population genomic analysis showed that the wild B. oleracea populations had the highest level of diversity and represents the most closely related population to modern-day horticultural B. oleracea. In addition, the WUSCHEL gene was found to play a decisive role in domestication and to be involved in cauliflower and broccoli curd formation. We also illustrate the loss of disease-resistance genes during selection for domestication. Our results provide new insights into the domestication of B. oleracea and will facilitate the future genetic improvement of Brassica crops.

Combination of Transcriptomics and Proteomics Reveals Differentially Expressed Genes and Proteins in the Skin of EDAR Gene-Targeted and Wildtype Cashmere Goats.

Cashmere goats play a pivotal role in the animal hair industry and are economically valuable. Cashmere is produced through the periodic growth of secondary hair follicles. To improve their yield of cashmere, the regulatory mechanisms of cashmere follicle growth and development need to be analysed. Therefore, in this study, EDAR gene-targeted cashmere goats were used as an animal model to observe the phenotypic characteristics of abnormal hair growth and development at the top of the head. Transcriptomic and proteomic techniques were used to screen for differentially expressed genes and proteins. In total, 732 differentially expressed genes were identified, including 395 upregulated and 337 downregulated genes. In addition, 140 differentially expressed proteins were identified, including 69 upregulated and 71 downregulated proteins. These results provide a research target for elucidating the mechanism through which EDAR regulates hair follicle growth in cashmere goats. It also enriches the available data on the regulatory network involved in hair follicle growth.

Genome-Wide Identification and Functional Characterization of Stress Related Glyoxalase Genes in Brassica napus L.

Rapeseed (Brassica napus L.) is not only one of the most important oil crops in the world, but it is also an important vegetable crop with a high value nutrients and metabolites. However, rapeseed is often severely damaged by adverse stresses, such as low temperature, pathogen infection and so on. Glyoxalase I (GLYI) and glyoxalase II (GLYII) are two enzymes responsible for the detoxification of a cytotoxic metabolite methylglyoxal (MG) into the nontoxic S-D-lactoylglutathione, which plays crucial roles in stress tolerance in plants. Considering the important roles of glyoxalases, the GLY gene families have been analyzed in higher plans, such as rice, soybean and Chinese cabbage; however, little is known about the presence, distribution, localizations and expression of glyoxalase genes in rapeseed, a young allotetraploid. In this study, a total of 35 BnaGLYI and 30 BnaGLYII genes were identified in the B. napus genome and were clustered into six and eight subfamilies, respectively. The classification, chromosomal distribution, gene structure and conserved motif were identified or predicted. BnaGLYI and BnaGLYII proteins were mainly localized in chloroplast and cytoplasm. By using publicly available RNA-seq data and a quantitative real-time PCR analysis (qRT-PCR), the expression profiling of these genes of different tissues was demonstrated in different developmental stages as well as under stresses. The results indicated that their expression profiles varied among different tissues. Some members are highly expressed in specific tissues, BnaGLYI11 and BnaGLYI27 expressed in flowers and germinating seed. At the same time, the two genes were significantly up-regulated under heat, cold and freezing stresses. Notably, a number of BnaGLY genes showed responses to Plasmodiophora brassicae infection. Overexpression of BnGLYI11 gene in Arabidopsis thaliana seedlings confirmed that this gene conferred freezing tolerance. This study provides insight of the BnaGLYI and BnaGLYII gene families in allotetraploid B. napus and their roles in stress resistance, and important information and gene resources for developing stress resistant vegetable and rapeseed oil.

Settling Preference of Two Coexisting Aphid Species on the Adaxial and Abaxial Surfaces of Walnut Leaves.

Walnut dusky-veined aphid Panaphis juglandis (Goeze) and walnut green aphid Chromaphis juglandicola (Kaltenbach) cause economic losses and co-occur on walnut trees, but they have separate niche. Panaphis juglandis feeds on the upper (adaxial) surface of leaves while C. juglandicola feeds on the lower (abaxial) surface. Field surveys and controlled experiments in the field and laboratory were conducted to determine microhabitat selection by P. juglandis and C. juglandicola and the factors associated with this behavior. In the field, the two aphid species colonized a leaflet as follows: P. juglandis only, 16.5%; C. juglandicola only, 44.5%; and both species on same leaflet, 39%. C. juglandicola settled on the abaxial surface earlier than P. juglandis settled on the adaxial surface. P. juglandis showed the highest reproduction rate when they were in the erect position on the adaxial surface. C. juglandicola exhibited the highest reproduction rate when they were inverted and on the abaxial surface. Under a light intensity of 50,000 lux, 60.5% of C. juglandicola remained on the illuminated surface, while P. juglandis did not move from the illuminated surface. Through field and laboratory experiments, we found that P. juglandis preferred to settle on the adaxial surface and C. juglandicola preferred to settle on the abaxial surface. Leaf surface, gravity, and light were three physical factors affecting microhabitat selection by the two aphid species but light intensity was the key factor. This information will help to better understand the habitats of two aphid species, which may be helpful for walnut aphids management strategies such as the usage of insecticides option and spraying.

Genomic selection and genetic architecture of agronomic traits during modern rapeseed breeding.

Rapeseed (Brassica napus L.) is an important oil-producing crop for the world. Its adaptation, yield and quality have been considerably improved in recent decades, but the genomic basis underlying successful breeding selection remains unclear. Hence, we conducted a comprehensive genomic assessment of rapeseed in the breeding process based on the whole-genome resequencing of 418 diverse rapeseed accessions. We unraveled the genomic basis for the selection of adaptation and agronomic traits. Genome-wide association studies identified 628 associated loci-related causative candidate genes for 56 agronomically important traits, including plant architecture and yield traits. Furthermore, we uncovered nonsynonymous mutations in plausible candidate genes for agronomic traits with significant differences in allele frequency distributions across the improvement process, including the ribosome recycling factor (BnRRF) gene for seed weight. This study provides insights into the genomic basis for improving rapeseed varieties and a valuable genomic resource for genome-assisted rapeseed breeding.

Quantitative Assessment of Abiotic Stress on the Main Functional Phytochemicals and Antioxidant Capacity of Wheatgrass at Different Seedling Age.

The wheat seedlings of 6 days old were daily subjected to ultraviolet irradiation (irradiating for 5, 10, 20, 40, and 60 min/day, respectively), Polyethylene glycol 6000 (5, 10, 15, 20, 25% in 1/2 Hoagland solution, respectively), and salinity solution (10, 25, 50, 100, 200 mM in 1/2 Hoagland solution, respectively), while the control group (CK) was supplied only with the Hoagland solution. The wheatgrass was harvested regularly seven times and the total soluble polysaccharides, ascorbic acid, chlorophyll, total polyphenol, total triterpene, total flavonoid, and proanthocyanins content were tested. The antioxidant capacity was evaluated through 2,2'-azino-bis (3-ethylbenzthia-zoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging ability, and ferric ion reducing power. Technique for order preference by similarity to ideal solution (TOPSIS) mathematical model was adopted to comprehensively assess the functional phytochemicals of the different treatments. The results showed that the accumulation patterns of phytochemicals under abiotic stress were complex and not always upregulated or downregulated. The antioxidant activity and functional phytochemicals content of wheatgrass were significantly affected by both the stress treatments and seedling age, while the latter affected the chemicals more efficiently. The top five highest functional phytochemicals were observed in the 200 mM NaCl treated group on the 21st and 27th day, 25% PEG treated group on the 24th day, 200 mM NaCl treated group on the 24th day, and the group of 40 min/day ultraviolet exposure on 27th day.

Green Extraction of Phenolic Compounds from Lotus Seedpod (Receptaculum Nelumbinis) Assisted by Ultrasound Coupled with Glycerol.

Lotus Receptaculum Nelumbinis has been sparking wide research interests due to its rich phenolic compounds. In the present work, ultrasonic-assisted extraction coupled with glycerol was employed to extract phenolic compounds from Receptaculum Nelumbinis and the process was optimized using a response surface methodology with Box-Behnken design (BBD). The optimal conditions for the total phenolic content (TPC) extract were obtained: glycerol concentration of 40%, an extraction temperature of 66 °C, ultrasonic time of 44 min, and the solvent-to-solid ratio of 55 mL/g. Under these optimum extraction conditions, the extraction yield of TPC was 92.84 ± 2.13 mg gallic acid equivalents (GAE) /g. Besides, the antioxidant activities demonstrated the ability of free radical scavenging by four different methods that included 2,2-Diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing activity (RA) were 459.73 ± 7.07, 529.97 ± 7.30, 907.61 ± 20.28, and 983.66 ± 11.80 µmol TE/g, respectively. Six phenolic compounds were identified by ultra-high pressure liquid chromatography combined with triple-time-of-flight mass spectrophotometry (UPLC-Triple-TOF/MS) from the extracts. Meanwhile, Fourier transform infrared (FTIR) was conducted to identify the characteristic functional groups of the extracts and thus reflected the presence of polyphenols and flavonoids. Scanning electron microscopy (SEM) illustrated the microstructure difference of four treatments, which might explain the relationships between antioxidant activities and the structures of phenolic compounds.

Is Orius sauteri Poppius a Promising Biological Control Agent for Walnut Aphids? An Assessment from the Laboratory to Field.

Walnut aphids are major pests of walnut production with few commercially available natural enemies. We conducted laboratory and field experiments to evaluate the potential of Orius sauteri Poppius (Anthocoridae), a predatory bug, as a biological control agent against two walnut aphid species: the dusky-veined aphid (Panaphis juglandis Goeze) and the walnut aphid (Chromaphis juglandicola Kaltenbach). Both species co-occur on walnut trees; P. juglandis is distributed on the upper surface (adaxial) of leaves while C. juglandicola is found on the lower surface (abaxial) of leaves. Based on functional response experiments, O sauteri had a strong capacity for consuming both aphid species. Biocontrol efficacy of O. sauteri for each species in the laboratory and field experiments was high, 77% for P. juglandis and 80% for C. juglandicola, regardless if one or two predators being present. However, biocontrol efficacy declined 15-25% for C. juglandicola and 20-50% for P. juglandis when both aphid species were present on the same leaf. The efficacy of O. sauteri under (semi)-field conditions gave similar findings based on the percentage reduction of aphids and change in population growth rates of aphids. The reduced biocontrol efficacy of the predatory bug against mixed species populations of aphids can be explained by competition between the aphid species and differences in their preferred location on leaves. Our experiments showed that O. sauteri is a promising biocontrol agent, but biocontrol efficacy may decline when both aphid species are present on walnut trees. This should be considered in the commercial release of O. sauteri in walnut orchards to promote economic and environmental benefits of walnuts production.

A visual Hg2+ detection strategy based on distance as readout by G-quadruplex DNAzyme on microfluidic paper.

In this work, we have developed a simple, fast and visual Hg2+ detection strategy based on distance as readout on paper chip by the Hg2+-mediated formation of G-quadruplex-hemin DNAzymes. In the presence of Hg2+, the two oligonucleotides hybridize to form G-quadruplex DNA by T-Hg2+-T base pair, which was able to bind hemin to form the catalytically active G-quadruplex-hemin DNAzymes. Once DNAzymes were added to react with the precipitated 3,3,5,5-tetramethyl benzidine (TMB) immobilized on the sample area, a visible color band was produced, and the formed length was positively correlated with the concentration of Hg2+. This biosensor is capable of selectively detecting mercuric ions with good reproducibility and satisfactory dynamic range. The limit of detection was low to 0.23 nM. Therefore, this strategy not only provides a visual and quick screen of Hg2+, but also shows a promising future in monitoring analysis of other metal ions in POC diagnostic field.

Organosilica-Based Hollow Mesoporous Bilirubin Nanoparticles for Antioxidation-Activated Self-Protection and Tumor-Specific Deoxygenation-Driven Synergistic Therapy.

A major concern about glucose oxidase (GOx)-mediated cancer starvation therapy is its ability to induce serious oxidative damage to normal tissues through the massive production of H2O2 byproducts in the oxygen-involved glucose decomposition reaction, which may be addressed by using a H2O2 scavenger, known as an antioxidation agent. Surprisingly, H2O2 removal accelerates the aerobic glycometabolism of tumors by activating the H2O2-dependent "redox signaling" pathway of cancer cells. Simultaneous oxygen depletion further aggravates tumor hypoxia to increase the toxicity of a bioreductive prodrug, such as tirapazamine (TPZ), thereby improving the effectiveness of cancer starvation therapy and bioreductive chemotherapy. Herein, a "nitrogen-protected silica template" method is proposed to design a nanoantioxidant called an organosilica-based hollow mesoporous bilirubin nanoparticle (HMBRN), which can act as an excellent nanocarrier to codeliver GOx and TPZ. In addition to efficient removal of H2O2 for self-protection of normal tissues via antioxidation, GOx/TPZ-coloaded HMBRN can also rapidly deplete intratumoral glucose/oxygen to promote a synergistic starvation-enhanced bioreductive chemotherapeutic effect for the substantial suppression of solid tumor growth. Distinct from the simple combination of two treatments, this study introduces antioxidation-activated self-protection nanotechnology for the significant improvement of tumor-specific deoxygenation-driven synergistic treatment efficacy without additional external energy input, thus realizing the renaissance of precise endogenous cancer therapy with negligible side effects.

Highly efficient preparation of active S-phenyl-L-cysteine with tryptophan synthase using a chemoenzymatic method.

BACKGROUND: S-Phenyl-L-cysteine is regarded as having potential applicability as an antiretroviral/protease inhibitor for human immunodeficiency virus (HIV). In the present study, optically active S-phenyl-L-cysteine was prepared in a highly efficient manner from inexpensive bromobenzene using tryptophan synthase through a chemoenzymatic method. RESULTS: The chemoenzymatic method used a four-step reaction sequence. The process started with the reaction of magnesium and bromobenzene, followed by a Grignard reaction, and then hydrolysis and enzymatic synthesis using tryptophan synthase. Through this approach, S-phenyl-L-cysteine was chemoenzymatically synthesized using tryptophan synthase from thiophenol and L-serine as the starting material. CONCLUSIONS: High-purity, optically active S-phenyl-L-cysteine was efficiently and inexpensively obtained in a total yield of 81.3% (> 99.9% purity).

Self-assembled green tea polyphenol-based coordination nanomaterials to improve chemotherapy efficacy by inhibition of carbonyl reductase 1.

Nanomedicine has become a promising approach to improve cancer chemotherapy. It remains a major challenge how to enhance anti-drug efficacy and reduce side effects of anti-cancer drugs. Herein, we report a self-assembled nanoplatform (FDEP NPs) by integration of doxorubicin (DOX) and epigallocatechin-3-O-gallate (EGCG) with the help of coordination between Fe3+ ions and polyphenols. The EGCG from FDEP NPs could inhibit the expression of carbonyl reductase 1 (CBR1) protein and thereby inhibit the doxorubicinol (DOXOL) generation from DOX both in vitro and in vivo, thus the efficacy of DOX to cancerous cells is improved significantly. More importantly, the FDEP NPs could reduce cardiac toxicity and the DOX mediated toxicity to blood cells due to the repression of DOXOL production. Moreover, the blood half-life of FDEP NPs is longer than 23 h as determined by positron emission tomography (PET) imaging of biodistribution of radiolabelled NPs and HPLC measurement of plasma level of DOX, ensuring high tumor accumulation of FDEP NPs by enhanced permeability and retention (EPR) effect. The FDEP NPs also exhibited much improved antitumor effect over free drugs. Our work sheds new light on the engineering of nanomaterials for combination chemotherapy and may find unique clinical applications in the near future.

Revealing the Synergistic Mechanism of Multiple Components in Compound Fengshiding Capsule for Rheumatoid Arthritis Therapeutics by Network Pharmacology.

BACKGROUND: Compound Fengshiding capsule (CFC), is a Chinese formulation from herbal origin including Alangium platanifolium, Angelicae dahurica, Cynanchum paniculatum and Glycyrrhiza uralensis. CFC is widely used as clinical therapy against rheumatoid arthritis. However, its exact mechanism of action has not been explored yet. METHODS: In order to explore the synergistic mechanism of CFC, we designed a study adopting network pharmacology scheme to screen the action targets in relation to the CFC components. The study analyses target facts of salicin, paeonol, liquiritin and imperatorin from PubMed database, and explores the potential pharmacological targets of rheumatoid arthritis, cervical neuralgia and sciatica related diseases for their interaction. RESULTS: The results of boosted metabolic pathway showed that the chemical components of CFC interrupted many immune-related pathways, thus participating in immunity regulation of the body and playing a role in the treatment of rheumatism. Collectively, CFC has apoptotic, oxidative stress modulatory and anti-inflammatory effects that accumulatively serve for its clinical application against rheumatoid arthritis. CONCLUSION: Conclusively, our findings from present study reconnoiters and compacts systematic theoretical approach by utilizing the network pharmacology mechanism of four effective components for the treatment of rheumatism indicating sufficient potential drug targets associated with CFC against rheumatism. These interesting findings entreaties for further in vitro and in vivo studies on the mechanism of compound active ingredient against rheumatism.

Liquiritin from Glycyrrhiza uralensis Attenuating Rheumatoid Arthritis via Reducing Inflammation, Suppressing Angiogenesis, and Inhibiting MAPK Signaling Pathway.

Among the various treatments, induction of synoviocyte apoptosis by natural products during a rheumatoid arthritis (RA) pathological condition can be considered to have vast potential. However, it is unclear that liquiritin, a kind of natural flavonoid extracted from the roots of Glycyrrhiza uralensis, induced the apoptosis of the synovial membrane and its molecular mechanism. In this study, interleukin-1ß (IL-1ß)-RA-FLS cells were incubated with different concentrations of liquiritin. An MTT assay, Hoechst 33342 staining, JC-1 staining, and Western blot were used to check the viability, cell apoptosis, mitochondrial membrane potential changes, and the expression of related proteins, respectively. In vivo, a TUNEL assay and HE staining of tissue were used for histopathological evaluation. Our results showed that liquiritin significantly inhibited the proliferation of IL-1ß-induced-RA-FLS, promoted nuclear DNA fragmentation, and changed the mitochondrial membrane potential to accelerate cell apoptosis. Liquiritin downregulated the ratio of Bcl-2/Bax and inhibited the VEGF expression and phosphorylation of JNK and P38. Moreover, liquiritin improved the clinical score of rheumatism, inflammatory infiltration, and angiogenesis and induced apoptosis of the synovial tissue in vivo. Hence, liquiritin ameliorates RA by reducing inflammation, blocking MAPK signaling, and restraining angiogenesis.

Salicin from Alangium chinense Ameliorates Rheumatoid Arthritis by Modulating the Nrf2-HO-1-ROS Pathways.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder linked to oxidative stress of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). The effects and potential mechanism of salicin on inflammation and oxidative stress of RA-FLSs were examined by MTT, ELISA, and Western blot methods. Salicin significantly reduced cell viability (82.03 ± 7.06, P < 0.01), cytokines (47.70 ± 1.48 ng/L for TNF-α, 30.03 ± 3.49 ng/L for IL-6) ( P < 0.01), and matrix metalloproteinases-1/-3 expression ( P < 0.01) in IL-1ß-induced RA-FLSs and inhibited ROS generation and p65 phosphorylation ( P < 0.01) as compared with IL-1ß-induced treatment. Moreover, salicin promoted Nrf2 nuclear translocation (2.15 ± 0.21) and HO-1 expression (1.12 ± 0.05) and reduced ROS production in IL-1ß-induced RA-FLSs ( P < 0.01). Salicin not only reduced the collagen-induced arthritis by reducing the clinical score ( P < 0.01), inflammatory infiltration, and synovial hyperplasia in vivo but also suppressed the oxidative damage indexes (SOD 155.40 ± 6.53 U/mg tissue, MDA 152.80 ± 5.89 nmol/g tissue, GSH 50.98 ± 3.45 nmol/g tissue, and CAT 0.92 ± 0.10 U/g protein) ( P < 0.01) of ankle joint cells. Conclusively, our findings indicate that salicin ameliorates rheumatoid arthritis, which may be associated with oxidative stress and Nrf2-HO-1-ROS pathways in RA-FLSs.

An Integration of Genome-Wide Association Study and Gene Co-expression Network Analysis Identifies Candidate Genes of Stem Lodging-Related Traits in Brassica napus.

Lodging is a persistent problem which severely reduce yield and impair seed quality in rapeseed (Brassica napus L.). Enhancing stem strength (SS) has proven to be an effective approach to decrease lodging risk. In the present study, four interrelated stem lodging-related traits, including stem breaking resistance (SBR), stem diameter (SD), SS, and lodging coefficient (LC), were investigated among 472 rapeseed accessions. A genome-wide association study (GWAS) using Brassica 60K SNP array for stem lodging-related traits identified 67 significantly associated quantitative trait loci (QTLs) and 71 candidate genes. In parallel, a gene co-expression network based on transcriptome sequencing was constructed. The module associated with cellulose biosynthesis was highlighted. By integrating GWAS and gene co-expression network analysis, some promising candidate genes, such as ESKIMO1 (ESK1, BnaC08g26920D), CELLULOSE SYNTHASE 6 (CESA6, BnaA09g06990D), and FRAGILE FIBER 8 (FRA8, BnaC04g39510D), were prioritized for further research. These findings revealed the genetic basis underlying stem lodging and provided worthwhile QTLs and genes information for genetic improvement of stem lodging resistance in B. napus.

A paclitaxel prodrug with bifunctional folate and albumin binding moieties for both passive and active targeted cancer therapy.

Folate receptor (FR) has proven to be a valuable target for chemotherapy using folic acid (FA) conjugates. However, FA-conjugated chemotherapeutics still have low therapeutic efficacy accompanied with side effects, resulting from complications such as short circulation half-life, limited tumor delivery, as well as high kidney accumulation. Herein, we present a novel FA-conjugated paclitaxel (PTX) prodrug which was additionally conjugated with an Evans blue (EB) derivative for albumin binding. The resulting bifunctional prodrug prolonged blood circulation, enhanced tumor accumulation, and consequently improved tumor therapeutic efficacy. Methods: Fmoc-Cys(Trt)-OH was coupled onto PTX at the 7'-OH position for further synthesis of ester prodrug FA-PTX-EB. The targeting ability was investigated using confocal microscopy and flow cytometry. The pharmacokinetics of this bifunctional compound was also studied. Meanwhile, cell viability was evaluated in normal cells and three cancer cell lines by MTT assay. In vivo therapeutic effect was tested on FR-α overexpressing MDA-MB-231 tumor model. Results: Compared with free PTX, the FA-PTX, PTX-EB and FA-PTX-EB prodrugs increased circulation half-life in mice from 2.19 to 3.82, 4.41, and 7.51 h, respectively. Pharmacokinetics studies showed that the FA-PTX-EB delivered more PTX to tumors than FA-PTX and free PTX. In vitro and in vivo studies demonstrated that FA-EB-conjugated PTX induced potent antitumor activity. Conclusion: FA-PTX-EB showed prolonged blood circulation, enhanced drug accumulation in tumors, higher therapeutic index, and lower side effects than either free PTX or monofunctional FA-PTX and EB-PTX. The results support the potential of using EB for the development of long-acting therapeutics.

Apoptosis effects of imperatorin on synoviocytes in rheumatoid arthritis through mitochondrial/caspase-mediated pathways.

Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease associated with a potential imbalance between the growth and death of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). Imperatorin (IPT) is a naturally occurring furanocoumarin found in umbelliferous vegetables, citrus fruits, and some herbs. The effects of IPT on the proliferation and apoptosis of RA-FLSs and its potential underlying mechanisms have remained unclear. RA-FLSs obtained from RA patients were induced by interleukin-1ß (IL-1ß) and treated with IPT. Cell viability was determined by MTT assay. Apoptotic cell death was analyzed by Annexin V-FITC/PI double staining and Hoechst 33342 staining. The loss in the mitochondrial membrane potential (ΔΨm) was visualized on the basis of JC-1 staining via fluorescence microscopy, and protein expression changes were assessed by western blot, whereas in vivo studies were conducted in male Wistar rats followed by histopathological assessment via TUNEL assay and HE staining of tissues. The results showed that IPT significantly reduced cell viability, accelerated cell apoptosis and decreased matrix metalloproteinases-1/-3 expression in IL-1ß-induced RA-FLSs. Furthermore, IPT exposure was found to disrupt the ΔΨm compared to the IL-1ß-induced treatment. Moreover, IPT increased the release of mitochondrial cytochrome C, the ratio of Bax/Bcl-2, and the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase. In vivo studies showed that IPT not only significantly reduced the collagen induced arthritis by reducing synovial hyperplasia, and pannus formation but also enhanced the apoptotic index of ankle joint cells. Conclusively, our findings suggest that IPT inhibits cell proliferation and induces apoptosis in RA-FLSs that may be associated with mitochondrial/caspase-mediated signalling pathways.

Genome-wide analysis and expression profiles of glyoxalase gene families in Chinese cabbage (Brassica rapa L).

The glyoxalase pathway is composed of glyoxalase I (GLYI) and glyoxalase II (GLYII) and is responsible for the detoxification of a cytotoxic metabolite methylglyoxal (MG) into the nontoxic S-D-lactoylglutathione. The two glyoxalase enzymes play a crucial role in stress tolerance in various plant species. Recently, the GLY gene families have well been analyzed in Arabidopsis, rice and soybean, however, little is known about them in Chinese cabbage (Brassica rapa). Here, 16 BrGLYI and 15 BrGLYII genes were identified in the B. rapa genome, and the BrGLYI and BrGLYII proteins were both clustered into five subfamilies. The classifications, chromosomal distributions, gene duplications, exon-intron structures, localizations, conserved motifs and promoter cis-elements were also predicted and analyzed. In addition, the expression pattern of these genes in different tissues and their response to biotic and abiotic stresses were analyzed using publicly available data and a quantitative real-time PCR analysis (RT-qPCR). The results indicated that the expression profiles of BrGLY genes varied among different tissues. Notably, a number of BrGLY genes showed responses to biotic and abiotic stress treatments, including Plasmodiophora brassicae infection and various heavy metal stresses. Taken together, this study identifies BrGLYI and BrGLYII gene families in B. rapa and offers insight into their roles in plant development and stress resistance, especially in heavy metal stress tolerance and pathogen resistance.