Summary
The effective anti‐malarial drug artemisinin (AN) isolated from Artemisia annua is relatively expensive due to the low AN content in the plant as AN is only synthesized within the glandular ...trichomes. Therefore, genetic engineering of A. annua is one of the most promising approaches for improving the yield of AN. In this work, the AaMYB1 transcription factor has been identified and characterized. When AaMYB1 is overexpressed in A. annua, either exclusively in trichomes or in the whole plant, essential AN biosynthetic genes are also overexpressed and consequently the amount of AN is significantly increased. Artemisia AaMYB1 constitutively overexpressing plants displayed a greater number of trichomes. In order to study the role of AaMYB1 on trichome development and other possibly connected biological processes, AaMYB1 was overexpressed in Arabidopsis thaliana. To support our findings in Arabidopsis thaliana, an AaMYB1 orthologue from this model plant, AtMYB61, was identified and atmyb61 mutants characterized. Both AaMYB1 and AtMYB61 affected trichome initiation, root development and stomatal aperture in A. thaliana. Molecular analyses indicated that two crucial trichome activator genes are misexpressed in atmyb61 mutant plants and in plants overexpressing AaMYB1. Furthermore, AaMYB1 and AtMYB61 are also essential for gibberellin (GA) biosynthesis and degradation in both species by positively affecting the expression of the enzymes that convert GA9 into the bioactive GA4 as well as the enzymes involved in the degradation of GA4. Overall, these results identify AaMYB1/AtMYB61 as a key component of the molecular network that connects important biosynthetic processes, and reveal its potential value for AN production through genetic engineering.
Significance Statement
The biosynthetic pathway of artemisinin, an antimalarial and anticancer substance, only takes place in Artemisia annua glandular trichomes; however artemisinin content in this plant is too low to cover worldwide demand for the product. New research has identified AaMYB1 transcription factor that positively affects not only AN biosynthesis but also, as its orthologue AtMYB61, affect gibberellin biosynthesis and trichome proliferation; two diverse but connected processes necessary for improving AN yield in planta.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The present study reviewed the relevant recent literature regarding the development and application of oblique lumbar interbody fusion (OLIF), with a particular focus on its application and ...associated complications. The study evaluated the rationality of this technique and demonstrated the direction of future research by collecting data on previous operative outcomes and complications. A literature search was performed in Pubmed and Web of Science, including the following keywords and abbreviations: anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), direct lateral interbody fusion (DLIF), extreme lateral interbody fusion (XLIF), oblique lateral interbody fusion (OLIF), adjacent segment disease (ASD), and adult degenerative scoliosis (ADS). A search of literature published from January 2005 to January 2019 was conducted and all studies evaluating development and application of OLIF were included in the review. According to the literature, the indications for OLIF are various. OLIF has excellent orthopaedic effects in degenerative scoliosis patients and the incidence of bony fusion is higher than for other approaches. It also provides a better choice for revision surgery. It has various advantages in many aspects, but the complications cannot be ignored. As a new minimally invasive technique, the advantages of OLIF are obvious, but further evaluation is needed to compare its operation‐related data with that of traditional open surgery. In addition, more prospective studies are required to compare minimally invasive and open spinal surgery to confirm its specific efficacy, risk, advantages, learning curve, and ultimate clinical efficacy.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Six transcription factors of APETALA2/ethylene-response factor (AP2/ERF) family were cloned and analyzed in Artemisia annua. Real-time quantitative polymerase chain reaction (RT-Q-PCR) showed that ...AaORA exhibited similar expression patterns to those of amorpha-4,11-diene synthase gene (ADS), cytochrome P450-dependent hydroxylase gene (CYP71AV1) and double bond reductase 2 gene (DBR2) in different tissues of A. annua.
AaORA is a trichome-specific transcription factor, which is expressed in both glandular secretory trichomes (GSTs) and nonglandular T-shaped trichomes (TSTs) of A. annua. The result of subcellular localization shows that AaORA is targeted to the nuclei and the cytoplasm.
Overexpression and RNA interference (RNAi) of AaORA in A. annua regulated, positively and significantly, the expression levels of ADS, CYP71AV1, DBR2 and AaERF1. The up-regulated or down-regulated expression levels of these genes resulted in a significant increase or decrease in artemisinin and dihydroartemisinic acid. The results demonstrate that AaORA is a positive regulator in the biosynthesis of artemisinin.
Overexpression of AaORA in Arabidopsis thaliana increased greatly the transcript levels of the defense marker genes PLANT DEFENSIN1.2 (PDF1.2), HEVEIN-LIKE PROTEIN (HEL) and BASIC CHITINASE (B-CHI). After inoculation with Botrytis cinerea, the phenotypes of AaORA overexpression in A. thaliana and AaORA RNAi in A. annua demonstrate that AaORA is a positive regulator of disease resistance to B. cinerea.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Glandular trichomes are generally considered biofactories that produce valuable chemicals. Increasing glandular trichome density is a very suitable way to improve the productivity of these valuable ...metabolites, but little is known about the regulation of glandular trichome formation. Phytohormone jasmonate (JA) promotes glandular trichome initiation in various plants, but its mechanism is also unknown.
By searching transcription factors regulated by JA in Artemisia annua, we identified a novel homeodomain-leucine zipper transcription factor, HOMEODOMAIN PROTEIN 1 (AaHD1), which positively controls both glandular and nonglandular trichome initiations. Overexpression of AaHD1 in A. annua significantly increased glandular trichome density without harming plant growth. Consequently, the artemisinin content was improved.
AaHD1 interacts with A. annua jasmonate ZIM-domain 8 (AaJAZ8), which is a repressor of JA, thereby resulting in decreased transcriptional activity. AaHD1 knockdown lines show decreased sensitivity to JA on glandular trichome initiation, which indicates that AaHD1 plays an important role in JA-mediated glandular trichome initiation.
We identified a new transcription factor that promotes A. annua glandular trichome initiation and revealed a novel molecular mechanism by which a homeodomain protein transduces JA signal to promote glandular trichome initiation. Our results also suggested a connection between glandular and nonglandular trichome formations.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The IPSL‐CM6‐LR atmosphere‐ocean coupled model exhibits a pronounced multicentennial variability of the Atlantic meridional overturning circulation (AMOC), driven by delayed freshwater accumulation ...and release in the Arctic. The AMOC fluctuations are preceded by salinity‐driven density anomalies in the main deep convection sites in the Labrador and Greenland seas. During a strong AMOC, a combination of reduced sea ice volume and anomalous currents reduces the freshwater export from the Arctic and leads instead to a slow accumulation of freshwater in the central Arctic. Simultaneously, the saltier Atlantic inflow through the Barents Sea results in a positive salinity anomaly in the Eastern Arctic subsurface. When the surface Central Arctic freshwater pool finally reaches the Lincoln Sea, the oceanic currents around Greenland reorganize, leading to the export of the anomalous Arctic freshwater to the North Atlantic, enhancing the stratification in deep convection sites. The AMOC then decreases, positive salinity anomalies appear in the Central Arctic, and the variability switches to the opposite phase. These AMOC and sea ice fluctuations have broader climate impacts, with a strong AMOC leading to a mean warming of about 0.4°C north of 20°N, reaching up to 1°C in the Arctic lower troposphere during winter. In all seasons, a northward displacement of the intertropical convergence zone is also simulated.
Plain Language Summary
The North Atlantic Ocean is known to have large climate fluctuations emerging from the different components of the climate system and their interactions. These fluctuations play a crucial role in the North American and European climate or the Arctic sea ice. A proper understanding of such internal variations is key to attribute the observed climate changes to anthropogenic activities or to assess the skill of decadal forecast systems. However, investigations of the long‐term basin‐scale variations are restrained by the limited instrumental observations. Therefore, an atmosphere‐ocean general circulation model is used here to explore the low‐frequency variability. This model simulates a large variability in the North Atlantic with a period between 1 century and 1 millennium. We found that this variability owes its existence to the freshwater exchanges between the North Atlantic and Arctic. Such North Atlantic variability has important impacts, as typical positive anomalies of the Atlantic oceanic northward heat transport reduce the sea ice, warm up the whole Northern Hemisphere by 0.4°C, and shift northward the intertropical convergence zone.
Key Points
A centennial to multicentennial variability emerges from the North Atlantic and Arctic Ocean in the IPSL‐CM6A‐LR model
AMOC oscillations are driven by freshwater build‐up and release in the Arctic
The interplay between sea ice and oceanic freshwater export modulates the salinity anomalies in the Arctic
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The glandular secretory trichomes (GSTs) on Artemisia annua leaves have the capacity to secrete and store artemisinin, a compound which is the most effective treatment for uncomplicated malaria. An ...effective strategy to improve artemisinin content is therefore to increase the density of GSTs in A. annua. However, the formation mechanism of GSTs remains poorly understood.
To explore the mechanisms of GST initiation in A. annua, we screened myeloblastosis (MYB) transcription factor genes from a GST transcriptome database and identified a MIXTA transcription factor, AaMIXTA1, which is expressed predominantly in the basal cells of GST in A. annua. Overexpression and repression of AaMIXTA1 resulted in an increase and decrease, respectively, in the number of GSTs as well as the artemisinin content in transgenic plants.
Transcriptome analysis and cuticular lipid profiling showed that AaMIXTA1 is likely to be responsible for activating cuticle biosynthesis. In addition, dual-luciferase reporter assays further demonstrated that AaMIXTA1 could directly activate the expression of genes related to cuticle biosynthesis.
Taken together, AaMIXTA1 regulated cuticle biosynthesis and prompted GST initiation without any abnormal impact on the morphological structure of the GSTs and so provides a new way to improve artemisinin content in this important medicinal plant.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Artemisinin is a type of sesquiterpene lactone well known as an antimalarial drug, and is specifically produced in glandular trichomes of Artemisia annua. However, the regulatory network for the ...artemisinin biosynthetic pathway remains poorly understood. Exploration of trichome-specific transcription factors would facilitate the elucidation of regulatory mechanism of artemisinin biosynthesis.
The WRKY transcription factor GLANDULAR TRICHOME-SPECIFIC WRKY 1 (AaGSW1) was cloned and analysed in A. annua. AaGSW1 exhibited similar expression patterns to the trichome-specific genes of the artemisinin biosynthetic pathway and AP2/ERF transcription factor AaORA. A β-glucuronidase (GUS) staining assay further demonstrated that AaGSW1 is a glandular trichome-specific transcription factor.
AaGSW1 positively regulates CYP71AV1 and AaORA expression by directly binding to the W-box motifs in their promoters. Overexpression of AaGSW1 in A. annua significantly improves artemisinin and dihydroartemisinic acid contents; moreover, AaGSW1 can be directly regulated by AaMYC2 and AabZIP1, which are positive regulators of jasmonate (JA)-and abscisic acid (ABA)-mediated artemisinin biosynthetic pathways, respectively.
These results demonstrate that AaGSW1 is a glandular trichome-specific WRKY transcription factor and a positive regulator in the artemisinin biosynthetic pathway. Moreover, we propose that two trifurcate feed-forward pathways involving AaGSW1, CYP71AV1 and AaMYC2/AabZIP1 function in the JA/ABA response in A. annua.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Dendrobium officinale, an endangered Chinese herb, possesses extensive therapeutic effects and contains bioactive ingredients such as major polysaccharides, alkaloids, and minimal flavonoids. We ...first obtained the protocorm-like bodies (PLBs) of this plant through tissue culture in order to determine the distribution of the main secondary metabolites in each organelle and the PLBs. We then analyzed the correlation between gene expression level from comparative transcriptome sequencing and metabolite content in different organs to identify putative genes encoding enzymes involved in the biosynthesis of polysaccharides, alkaloids, and flavonoids. We used seeds as explants for protocorm induction and PLB propagation of D. officinale. The optimal medium formula for PLB propagation was 1/2 MS + alpha-NAA 0.5 mg*L.sup.- 1 + 6-BA 1.0 mg*L.sup.- 1 + 2, 4-D 1.5-2.0 mg*L.sup.- 1 + potato juice 100 g*L.sup.- 1. Stems, PLBs and leaves of D. officinale had the highest content of polysaccharides, alkaloids and flavonoids, respectively. Naringenin was only produced in stem; however, PLBs with high alkaloid content can replace other organs producing alkaloids. The hot water extraction method outperformed the ultrasound-assisted extraction method for extracting polysaccharides from D. officinale. A comparative transcriptome analysis of PLBs and leaves of D. officinale revealed differential expression of genes encoding enzymes involved in polysaccharide, alkaloid and flavonoid biosynthetic pathways. Putative genes encoding enzymes involved in these biosynthetic pathways were identified. Notably, we identified genes encoding the alkaloid biosynthesis enzymes strictosidine beta-D-Glucosidase, geissoschizine synthase and vinorine synthase in D. officinale. The identification of candidate genes encoding enzymes involved in metabolite biosynthesis will help to explore and protect this endangered species and facilitate further analysis of the molecular mechanism of secondary metabolite biosynthesis in D. officinale.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Purpose
The purpose of this paper is to evaluate the clinical and radiographic outcomes of oblique lumbar interbody fusion (OLIF) to perform in L4/5 degenerative lumbar spondylolisthesis ...(DLS) patients who diagnosed with osteopenia.
Methods
From December 2018 to 2021 March, 94 patients were diagnosed with degenerative spondylolisthesis underwent OLIF and divided into two groups with different bone mineral density. Anterolateral screw and rod instrumentation was applied in two groups. The primary outcomes were VAS, JOA and ODI. The secondary outcomes included disc height (DH), cross-sectional height of the intervertebral foramina (CSH), cross-sectional area of the dural sac (CSA), lumbar lordorsis (LL), pelvic titlt (PT), pelvic incidence (PI) and sacrum slop (SS).
Results
All patients finished at least 1 years follow-up with 21.05 ± 4.42 months in the group A and 21.09 ± 4.28 months in the group B. The clinical symptoms were evaluated by VAS, JOA and ODI and 94 patients showed good outcomes at final follow-up (
P
< 0.05), with significant increases in DH, CSH and CSA. In group A, DH increased from 8.54 ± 2.48 to 11.11 ± 2.63 mm, while increased from 8.60 ± 2.29 to 11.23 ± 1.88 were recorded in group B. No statistical difference was found in DH between the two groups (
P
> 0.05). The cage subsidence was 1.14 ± 0.83 mm in group A and 0.87 ± 1.05 mm in group B (
P
> 0.05). There was no significant difference in the adjusted parameters of spino-pelvic between two groups (
P
> 0.05).
Conclusion
Oblique lumbar interbody fusion with anterolateral screw and rod instrumentation is feasible to be performed in osteopenia patients who diagnosed with degenerative spondylolisthesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Functionally graded triply periodic minimal surface (TPMS) structures are characterized by their various structures and mechanical properties, thereby exhibiting better mechanical performance than ...uniform structures. At present, most graded TPMS structures in studies possess unidirectional variable densities. However, when performing lattice optimization on an actual engineering model, the required multidirectional graded TPMS structure still relies on manual work, including parameter adjustment and modelling, so the optimization process is cumbersome and the design is suboptimal. In this paper, a new design method is proposed that realizes the stable and adaptive generation and optimization of functionally graded TPMS structures. This procedure is divided into two stages. In the preparation stage, the performance regulation of the TPMS and the values of von Mises stress are obtained from mesoscopic and macroscopic scales, respectively. In the optimization stage, optimization algorithms based on voxels are proposed so that functionally graded TPMS structures can be automatically obtained in different situations. Based on the simulation results, the compressive properties of our optimized design improves by 25.23% compared with that of the uniform structure and 8.63% compared with the functionally graded TPMS structure with topology optimization, which confirms the effectiveness and robustness of the proposed method.
Display omitted
•A new design method of graded triply periodic minimal surfaces structure was proposed•Analysis and processing were based on voxels to avoid discontinuity within the model•The design procedure was adaptive and stable because of the adaptive algorithm•Combined with the simulation results, the differences between other strategies were analyzed
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP