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Cytochromes P450 monooxygenases (CYP450s) constitute the largest enzymic protein family that is widely present in plants, animals, and microorganisms, participate in numerous metabolic pathways, and play diverse roles in development, metabolism, and defense. Rapeseed (Brassica napus) is an important oil crop worldwide and have many versions of reference genome. However, there is no systemically comparative genome-wide analysis of CYP450 family genes in rapeseed and its parental species B. rapa and B. oleracea. In this study, we identified 765, 293 and 437 CYP450 genes in B. napus, B. rapa and B. oleracea, respectively, which were unevenly located in A01-A10 and/or C01-C09 chromosomes in corresponding species. Phylogenetic relationship analysis indicated that 1745 CYP450 proteins from three Brassica species and Arabidopsis were divided into 4 groups. Whole genome duplication (WGD) or segmental duplication resulted in gene expansion of CYP450 family in three Brassica species. There were 33-83 SSR loci in CYP450 genes of three Brassica species, and numerous transcription factor binding sites were identified in their promoters. A total of 459-777 miRNAs were predicted to target 174-426 CYP450 genes in three Brassica species. Based on transcriptome data, BnCYP450s, BrCYP450s and BoCYP450s were differentially expressed in various tissues. There existed numerous BnCYP450 DEGs in response to pathogens and abiotic stresses. Besides, many BnCYP450 DEGs were involved in the regulation of important traits, such as seed germination, seed ALA content, and yellow-seed. The qRT-PCR experiment confirmed the transcriptome analysis results by validating two representative Sclerotinia-responsive BnCYP450 DEGs as an example. Three BnCYP450s genes (CYP707A1, CYP81F1, CYP81H1) might be regulated by seed-specific transcription factors BnTT1 and BnbZIP67 to participate in the development and metabolism of seed coat and embryo by undertaking related metabolic reactions.
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Two-dimensional (2D) auxetic materials have recently attracted considerable research interest due to their excellent mechanical properties and diverse applications, surpassing those of three-dimensional (3D) materials. This study focuses on the theoretical prediction of mechanical properties and auxeticity in 2D M2X (M = Cu, Ag, Au; X = S, Se, Te) monolayers using first-principles calculations. Our results indicate that the dynamically stable monolayers include low-energy α-Cu2S, α-Cu2Se, α-Cu2Te, ß-Ag2S, ß-Ag2Se, α-Ag2Te, ß-Au2S, ß-Au2Se and α-Au2Te. These M2X monolayers possess positive Poisson's ratios (PR) ranging from 0.09 to 0.52, as well as Young's moduli ranging from 19.92 to 35.42 N m-1 in x and y directions. Specially, α-Cu2S exhibits the lowest negative PR in θ = 45° × n (n = 1, 2, 3, 4) directions. The Poisson's function (PF) can be adjusted by increasing tensile strains. The ß-phase monolayers exhibit positive PF with a linear change. Interestingly, the transition from positive to negative PF occurs in the α-Cu2S and α-Ag2Te monolayers at strains greater than +3% and +4%, respectively, while the α-Cu2Se, α-Cu2Te and α-Au2Te monolayers maintain positive PF within the range of 0% to +6% strains. Furthermore, taking α-Cu2S (α-Cu2Te) as an example, the mechanism underlying negative (positive) PF is demonstrated to involve increased (decreased) bond angles, decreased thickness, and weakened (enhanced) d(M)-p(X) orbital coupling. The findings of this study not only enrich the family of 2D group-11 chalcogenides but also provide insights into their mechanical properties, thereby expanding their potential applications in mechanics.
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Using first-principles calculations, we systematically investigate the electronic properties, chiral skyrmions and bimerons in two-dimensional (2D) Janus CrXY (X, Y = S, Se, Te, Cl, Br, I, and X ≠ Y) monolayers. We found that the categories of nonmagnetic atoms (X and Y in CrXY) determine whether CrXY is a ferromagnetic metal or a semiconductor. Unexpectedly, the CrBrS monolayer of these CrXY materials is a room temperature ferromagnetic semiconductor with a Curie temperature of 303 K, and it possesses an off-plane magnetic anisotropy energy of 0.06 meV. Besides, a strong Dzyaloshinskii-Moriya interaction (DMI) of 3.10 meV is found in CrTeI and is mainly induced by the strong spin-orbit coupling of the nonmagnetic atoms Te(I) rather than that of the magnetic Cr atoms. Furthermore, using micromagnetic simulations, skyrmions can be stabilized in CrSeBr without external magnetic fields. More importantly, the bimerons in CrSeCl with in-plane magnetic anisotropy can be transformed into skyrmions or a ferromagnetic state by controlling the direction of external magnetic fields. Our work investigates fourteen kinds of Janus monolayers, serving as guidelines for materials research on DMI, skyrmions and bimerons.
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As alternative disease models, other than 2D cell lines and patient-derived xenografts, organoids have preferable in vivo physiological relevance. However, both endogenous and exogenous limitations impede the development and clinical translation of these organoids. Fortunately, colloidal photonic crystals (PCs), which benefit from favorable biocompatibility, brilliant optical manipulation, and facile chemical decoration, have been applied to the engineering of organoids and have achieved the desirable recapitulation of the ECM niche, well-defined geometrical onsets for initial culture, in situ multiphysiological parameter monitoring, single-cell biomechanical sensing, and high-throughput drug screening with versatile functional readouts. Herein, we review the latest progress in engineering organoids fabricated from colloidal PCs and provide inputs for future research.
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Óptica y Fotónica , Organoides , Humanos , Línea CelularRESUMEN
Drug delivery systems (DDSs) are designed to deliver therapeutic agents to specific target sites while minimizing systemic toxicity. Recent developments in drug-loaded DDSs have demonstrated promising characteristics and paved new pathways for cancer treatment. Light, a prevalent external stimulus, is widely utilized to trigger drug release. However, conventional light sources primarily concentrate on the ultraviolet (UV) and visible light regions, which suffer from limited biological tissue penetration. This limitation hinders applications for deep-tissue tumor drug release. Given their deep tissue penetration and well-established application technology, X-rays have recently received attention for the pursuit of controlled drug release. With precise spatiotemporal and dosage controllability, X-rays stand as an ideal stimulus for achieving controlled drug release in deep-tissue cancer therapy. This article explores the recent advancements in using X-rays for stimulus-triggered drug release in DDSs and delves into their action mechanisms.
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Nanopartículas , Neoplasias , Humanos , Rayos X , Liberación de Fármacos , Sistemas de Liberación de Medicamentos , Luz , Preparaciones Farmacéuticas , Neoplasias/tratamiento farmacológicoRESUMEN
Modern people generally suffer from α-linolenic acid (ALA) deficiency, since most staple food oils are low in ALA content. Thus, the enhancement of ALA in staple oil crops is of importance. In this study, the FAD2 and FAD3 coding regions from the ALA-king species Perilla frutescens were fused using a newly designed double linker LP4-2A, driven by a seed-specific promoter PNAP, and engineered into a rapeseed elite cultivar ZS10 with canola quality background. The mean ALA content in the seed oil of PNAP:PfFAD2-PfFAD3 (N23) T5 lines was 3.34-fold that of the control (32.08 vs 9.59%), with the best line being up to 37.47%. There are no significant side effects of the engineered constructs on the background traits including oil content. In fatty acid biosynthesis pathways, the expression levels of structural genes as well as regulatory genes were significantly upregulated in N23 lines. On the other hand, the expression levels of genes encoding the positive regulators of flavonoid-proanthocyanidin biosynthesis but negative regulators of oil accumulation were significantly downregulated. Surprisingly, the ALA level in PfFAD2-PfFAD3 transgenic rapeseed lines driven by the constitutive promoter PD35S was not increased or even showed a slight decrease due to the lower level of foreign gene expression and downregulation of the endogenous orthologous genes BnFAD2 and BnFAD3.
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Brassica napus , Brassica rapa , Perilla , Humanos , Brassica napus/genética , Brassica napus/metabolismo , Ácido alfa-Linolénico/química , Ácido Graso Desaturasas/genética , Ácido Graso Desaturasas/metabolismo , Brassica rapa/genética , Brassica rapa/metabolismo , Semillas/genética , Semillas/metabolismo , Aceites/metabolismoRESUMEN
Chia (Salvia hispanica) is a functional food crop with high α-linolenic acid (ALA), the omega-3 essential fatty acid, but its worldwide plantation is limited by cold-intolerance and strict short-photoperiod flowering feature. Fatty acid desaturases (FADs) are responsible for seed oil accumulation, and play important roles in cold stress tolerance of plants. To date, there is no report on systemically genome-wide analysis of FAD genes in chia (ShiFADs). In this study, 31 ShiFAD genes were identified, 3 of which contained 2 alternative splicing transcripts, and they were located in 6 chromosomes of chia. Phylogenetic analysis classified the ShiFAD proteins into 7 groups, with conserved gene structure and MEME motifs within each group. Tandem and segmental duplications coursed the expansion of ShiFAD genes. Numerous cis-regulatory elements, including hormone response elements, growth and development elements, biotic/abiotic stress response elements, and transcription factor binding sites, were predicted in ShiFAD promoters. 24 miRNAs targeting ShiFAD genes were identified at whole-genome level. In total, 15 SSR loci were predicted in ShiFAD genes/promoters. RNA-seq data showed that ShiFAD genes were expressed in various organs with different levels. qRT-PCR detection revealed the inducibility of ShiSAD2 and ShiSAD7 in response to cold stress, and validated the seed-specific expression of ShiSAD11a. Yeast expression of ShiSAD11a confirmed the catalytic activity of its encoded protein, and its heterologous expression in Arabidopsis thaliana significantly increased seed oleic acid content. This work lays a foundation for molecular dissection of chia high-ALA trait and functional study of ShiFAD genes in cold tolerance.
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Ácido Graso Desaturasas , Salvia , Ácido Graso Desaturasas/genética , Ácido Graso Desaturasas/metabolismo , Salvia hispanica , Filogenia , Salvia/genética , Salvia/metabolismo , Aceites de Plantas/química , Semillas/metabolismoRESUMEN
MYB transcription factors are major actors regulating plant development and adaptability. Brassica napus is a staple oil crop and is hampered by lodging and diseases. Here, four B. napus MYB69 (BnMYB69s) genes were cloned and functionally characterized. They were dominantly expressed in stems during lignification. BnMYB69 RNA interference (BnMYB69i) plants showed considerable changes in morphology, anatomy, metabolism and gene expression. Stem diameter, leaves, roots and total biomass were distinctly larger, but plant height was significantly reduced. Contents of lignin, cellulose and protopectin in stems were significantly reduced, accompanied with decrease in bending resistance and Sclerotinia sclerotiorum resistance. Anatomical detection observed perturbation in vascular and fiber differentiation in stems, but promotion in parenchyma growth, accompanied with changes in cell size and cell number. In shoots, contents of IAA, shikimates and proanthocyanidin were reduced, while contents of ABA, BL and leaf chlorophyll were increased. qRT-PCR revealed changes in multiple pathways of primary and secondary metabolisms. IAA treatment could recover many phenotypes and metabolisms of BnMYB69i plants. However, roots showed trends opposite to shoots in most cases, and BnMYB69i phenotypes were light-sensitive. Conclusively, BnMYB69s might be light-regulated positive regulators of shikimates-related metabolisms, and exert profound influences on various internal and external plant traits.
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Graphene-based (G-based) heterostructures have recently attracted considerable research interest in the field of two-dimensional nanodevices owing to their superior properties compared with those of separate monolayers. In this study, the electronic properties and Schottky barrier heights (SBHs) of G/XAu4Y (X, Y = Se, Te) heterostructures were systematically analyzed through first-principles calculations. G/SeAu4Se, G/SeAu4Te, and G/TeAu4Se are n-type Schottky contacts with Φn = 0.40, 0.38, and 0.55 eV respectively, whereas G/TeAu4Te is a p-type Schottky contact with Φp = 0.39 eV. In G-based heterostructures consisting of SeAu4Te that has a 0.22-Debye intrinsic dipole moment, the intrinsic dipole moments in different directions enhance or weaken the interfacial dipole moments corresponding to the charge transfer at the interface, resulting in different Φn values of G/SeAu4Te and G/TeAu4Se. Furthermore, vertical strain and external electric field, which influence charge transfer, are applied to G/XAu4Y heterostructures to modulate their SBHs. Taking G/TeAu4Te as an example, the p-type contact transforms into an almost ohmic contact with decreasing vertical strain or positive external electric field. The findings of this study can provide insights into the fundamental properties of G/XAu4Y for further research.
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In recent years, considerable attention has been paid to the research of peculiar magnetism in two-dimensional (2D) van der Waals (vdW) layered materials. Here, we unveil the major features and deep physical mechanisms of a magnetic phase transition and magnetic anisotropy switching in monolayer CrTe2 and antiferromagnetic (AFM) skyrmions in bilayer CrTe2via first-principles calculations and micromagnetic simulations. We find that a magnetic phase transition from stripy-type AFM to ferromagnetic (FM) order can be induced by applying a tensile strain of 3%. More interestingly, the magnetic easy axis can be switched between in-plane and off-plane via adjusting the magnitude of strain. Besides, the topologically protected bilayer AFM skyrmion is stabilized by a large Dzyaloshinskii-Moriya interaction (DMI) of 1.43 meV and a skyrmion lattice can be induced by a magnetic field of 6.9 T at 100 K. Different from the monolayer magnetic skyrmion, the bilayer AFM skyrmion is more promising in spintronic nanodevices owing to the suppressed skyrmion Hall effect. Our findings clarify the underlying mechanisms of the strain-tunable magnetic phase transition, magnetic anisotropy switching and bilayer AFM skyrmions in vdW magnet CrTe2, and also highlight the promising applications of CrTe2 in next-generation information storage devices.
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Using first-principles calculations and micro-magnetic simulations, we propose a Janus MnSbBiSe2Te2 (MSBST) monolayer derived from the MnBi2Te4 (MBT) ferromagnet and investigate the influence of biaxial strain on the electronic structures, topological characteristics and spin textures. Different from pristine MBT with an out-of-plane easy axis, the anisotropy of MSBST prefers an in-plane direction. Intriguingly, switching the easy axis direction of MSBST will significantly modify the band structure. Topological phase transition can be achieved by applying a compressive strain, making MSBST become a topological insulator with . Moreover, due to the inherent inversion asymmetry of Janus MSBST, a large Dzyaloshinskii-Moriya interaction (DMI) is induced for generating and stabilizing skyrmions. By micro-magnetic simulations, the results of spin textures show that the skyrmions phase can be achieved in MSBST with an external magnetic field of 0.8 T. Our findings provide guidelines for the development and application of spintronic devices with nontrivial topological properties and a large DMI.
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In recent years, great effort has been made in the study of two-dimensional (2D) van der Waals ferromagnets that can stabilize peculiar chiral spin textures, such as magnetic skyrmions and merons. Here, by first-principles calculations and micromagnetic simulations, we systematically investigate the in-plane magnetic anisotropy, Dzyaloshinskii-Moriya interaction (DMI) and magnetic merons in a Mn2I3Br3 monolayer. Mn2I3Br3 exhibits half-metallic behavior with a large band gap (â¼2.7 eV) for spin-down electrons, but is gapless for spin-up ones. In addition, unlike most 2D ferromagnets with an off-plane magnetic easy axis and negligible DMI, the magnetic easy axis of Mn2I3Br3 is in-plane, with a large magnetic anisotropy energy of -13.2 meV and a strong DMI of 4.6 meV, which are mainly induced by the strong spin-orbital coupling of I atoms, microscopically. In particular, spontaneous magnetic merons, stabilized by the DMI, can exist in a wide magnetic field range (0-6 T). Our work not only provides important guidelines for the investigation of the DMI and merons in half-metallic materials, but also demonstrates the Mn2I3Br3 monolayer as an ideal platform to explore the deep physics of magnetic merons and as a promising candidate for magnetic storage devices, as well as spin filters.
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Non-specific lipid transfer proteins (nsLTPs) are small cysteine-rich basic proteins which play essential roles in plant growth, development and abiotic/biotic stress response. However, there is limited information about the nsLTP gene (BnLTP) family in rapeseed (Brassica napus). In this study, 283 BnLTP genes were identified in rapeseed, which were distributed randomly in 19 chromosomes of rapeseed. Phylogenetic analysis showed that BnLTP proteins were divided into seven groups. Exon/intron structure and MEME motifs both remained highly conserved in each BnLTP group. Segmental duplication and hybridization of rapeseed's two sub-genomes mainly contributed to the expansion of the BnLTP gene family. Various potential cis-elements that respond to plant growth, development, biotic/abiotic stresses, and phytohormone signals existed in BnLTP gene promoters. Transcriptome analysis showed that BnLTP genes were expressed in various tissues/organs with different levels and were also involved in the response to heat, drought, NaCl, cold, IAA and ABA stresses, as well as the treatment of fungal pathogens (Sclerotinia sclerotiorum and Leptosphaeria maculans). The qRT-PCR assay validated the results of RNA-seq expression analysis of two top Sclerotinia-responsive BnLTP genes, BnLTP129 and BnLTP161. Moreover, batches of BnLTPs might be regulated by BnTT1 and BnbZIP67 to play roles in the development, metabolism or adaptability of the seed coat and embryo in rapeseed. This work provides an important basis for further functional study of the BnLTP genes in rapeseed quality improvement and stress resistance.
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Brassica napus , Brassica rapa , Brassica napus/metabolismo , Brassica rapa/genética , Brassica rapa/metabolismo , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Filogenia , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genéticaRESUMEN
Porous silicon nanoparticles (pSiNPs) are widely utilized as drug carriers due to their excellent biocompatibility, large surface area, and versatile surface chemistry. However, the dispersion in pore size and biodegradability of pSiNPs arguably have hindered the application of pSiNPs for controlled drug release. Here, a step-changing solution to this problem is described involving the design, synthesis, and application of three different linker-drug conjugates comprising anticancer drug doxorubicin (DOX) and different stimulus-cleavable linkers (SCLs) including the photocleavable linker (ortho-nitrobenzyl), pH-cleavable linker (hydrazone), and enzyme-cleavable linker (ß-glucuronide). These SCL-DOX conjugates are covalently attached to the surface of pSiNP via copper (I)-catalyzed alkyne-azide cycloaddition (CuAAC, i.e., click reaction) to afford pSiNP-SCL-DOXs. The mass loading of the covalent conjugation approach for pSiNP-SCL-DOX reaches over 250 µg of DOX per mg of pSiNPs, which is notably twice the mass loading achieved by noncovalent loading. Moreover, the covalent conjugation between SCL-DOX and pSiNPs endows the pSiNPs with excellent stability and highly controlled release behavior. When tested in both in vitro and in vivo tumor models, the pSiNP-SCL-DOXs induces excellent tumor growth inhibition.
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Nanopartículas , Neoplasias , Doxorrubicina/farmacología , Portadores de Fármacos , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Porosidad , SilicioRESUMEN
Mitochondrial DNA (mtDNA) is the genetic information of mitochondrion, and its structure is circular double-stranded. Despite the diminutive size of the mitochondrial genome, mtDNA mutations are an important cause of mitochondrial diseases which are characterized by defects in oxidative phosphorylation (OXPHOS). Mitochondrial diseases are involved in multiple systems, particularly in the organs that are highly dependent on aerobic metabolism. The diagnosis of mitochondrial disease is more complicated since mtDNA mutations can cause various clinical symptoms. To realize more accurate diagnosis and treatment of mitochondrial diseases, the detection of mtDNA and the design of drugs acting on it are extremely important. Over the past few years, many probes and therapeutic drugs targeting mtDNA have been developed, making significant contributions to fundamental research including elucidation of the mechanisms of mitochondrial diseases at the genetic level. In this review, we summarize the structure, function, and detection approaches for mtDNA. The most current topics in this field, such as mechanistic exploration and treatment of mtDNA mutation-related disorders, are also reviewed. Specific attention is given to discussing the design and development of these probes and drugs for mtDNA. We hope that this review will provide readers with a comprehensive understanding of the importance of mtDNA, and promote the development of effective molecules for theragnosis of mtDNA mutation-related diseases.
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ADN Mitocondrial/antagonistas & inhibidores , Enfermedades Mitocondriales/tratamiento farmacológico , Quinolinas/farmacología , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Humanos , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/metabolismo , Mutación , Quinolinas/químicaRESUMEN
In this study, the semitendinosus of horse meat was used as the raw material. The study assessed the variation of the tenderness of horse meat during postmortem aging through the injection of papain, bromelain and fungal protease. The cooking loss of the horse meat became worse during postmortem aging. Low concentration of protease improved water retention properties of horse meat. Papain, bromelain and fungal protease had significant influence on MFI and shear force. MFI increased obviously but the shear force decreased significantly with the addition of more protease (p <0.05). During postmortem aging, many small molecules popeptide appeared in treatment group. Myosin light chain 2, 20 KDa, 32 KDa and 75 KDa bands appeared at first, however later they disappeared in the group with high concentration of protease treatment in addition to the disappearance of Desmin and Troponin I. The muscle fiber, perimysium and endomysium were degraded because of papain, bromelain and fungal protease treatment. More muscle fiber fragments appeared during postmortem aging.Thus, the tenderness and eating quality of horse meat were improved by adding three kinds of protease.
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Mitochondria are vital subcellular organelles that generate most cellular chemical energy, regulate cell metabolism and maintain cell function. Mitochondrial dysfunction is directly linked to numerous diseases including neurodegenerative disorders, diabetes, thyroid squamous disease, cancer and septicemia. Thus, the design of specific mitochondria-targeting molecules and the realization of real-time acquisition of mitochondrial activity are powerful tools in the study and treatment of mitochondria dysfunction in related diseases. Recent advances in mitochondria-targeting agents have led to several important mitochondria chemical probes that offer the opportunity for selective targeting molecules, novel biological applications and therapeutic strategies. This review details the structural and physiological functional characteristics of mitochondria, and comprehensively summarizes and classifies mitochondria-targeting agents. In addition, their pros and cons and their related chemical biological applications are discussed. Finally, the potential biomedical applications of these agents are briefly prospected.
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Plastidial Δ12 fatty acid desaturase (FAD6) is a key enzyme for linoleic acid (LA) and α-linolenic acid (ALA) biosynthesis. Chia (Salvia hispanica L.) is a revived omega-3 plant source that is richest in ALA level. In this study, based on the RACE method, one full-length cDNA sequence encoding FAD6, named ShFAD6, was isolated from chia. There exist three alternative transcription start sites and five alternative poly(A) tailing sites in ShFAD6. The 5'UTR of ShFAD6 contains a purine-stretch of 44 bp. ShFAD6 has an ORF of 1335 bp encoding a 444 aa protein of 51.33 kDa. ShFAD6 contains a conserved Delta12-FADS-like domain together with three strong trans-membrane helices and three histidine motifs. There also exists a chloroplast transmit peptide in ShFAD6 N-terminal. Phylogenetic analyses validated its identity of dicot FAD6 protein and suggested some critical evolutionary features of plant FAD6 genes. Heterologous yeast expression confirmed the catalytic activity of ShFAD6. The qRT-PCR assay showed that ShFAD6 is mainly expressed in leaves, stems, flowers, buds and early-stage seeds, and also responded to various stresses and hormone treatments. Under Sclerotinia infection, qRT-PCR and fluorescence imaging illustrated the possible correlation of ShFAD6 expression and photosynthesis. This study provides insight for further function study of ShFAD6 in oil quality improvement in staple oilseed crops as well as stress response and adaptation in plants.
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Ácido Graso Desaturasas/metabolismo , Regulación de la Expresión Génica de las Plantas , Enfermedades de las Plantas/genética , Proteínas de Plantas/metabolismo , Salvia/metabolismo , Secuencia de Aminoácidos , Ascomicetos/fisiología , Secuencia de Bases , Clonación Molecular , Ácido Graso Desaturasas/genética , Filogenia , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/genética , Salvia/genética , Salvia/crecimiento & desarrollo , Salvia/microbiología , Semillas/genética , Semillas/crecimiento & desarrollo , Semillas/metabolismo , Semillas/microbiología , Homología de Secuencia de AminoácidoRESUMEN
Stimulus-cleavable nanoscale drug delivery systems are receiving significant attention owing to their capability of achieving exquisite control over drug release via the exposure to specific stimuli. Central to the construction of such systems is the integration of cleavable linkers showing susceptibility to one stimulus or several stimuli with drugs, prodrugs or fluorogenic probes on the one hand, and nanocarriers on the other hand. This review summarises recent advances in stimulus-cleavable linkers from various research areas and the corresponding mechanisms of linker cleavage and biological applications. The feasibility of extending their applications to the majority of nanoscale drug carriers including nanomaterials, polymers and antibodies are further highlighted and discussed. This review also provides general design guidelines to incorporate stimulus-cleavable linkers into nanocarrier-based drug delivery systems, which will hopefully spark new ideas and applications.
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Sistemas de Liberación de Medicamentos , Nanopartículas/química , Portadores de Fármacos/química , HumanosRESUMEN
Sclerotinia sclerotiorum (Ss) is a devastating fungal pathogen that causes Sclerotinia stem rot in rapeseed (Brassica napus), and is also detrimental to mulberry and many other crops. A wild mulberry germplasm, Morus laevigata, showed high resistance to Ss, but the molecular basis for the resistance is largely unknown. Here, the transcriptome response characteristics of M. laevigata to Ss infection were revealed by RNA-seq. A total of 833 differentially expressed genes (DEGs) were detected after the Ss inoculation in the leaf of M. laevigata. After the GO terms and KEGG pathways enrichment analyses, 42 resistance-related genes were selected as core candidates from the upregulated DEGs. Their expression patterns were detected in the roots, stems, leaves, flowers, and fruits of M. laevigata. Most of them (30/42) were specifically or mainly expressed in flowers, which was consistent with the fact that Ss mainly infects plants through floral organs, and indicated that Ss-resistance genes could be induced by pathogen inoculation on ectopic organs. After the Ss inoculation, these candidate genes were also induced in the two susceptible varieties of mulberry, but the responses of most of them were much slower with lower extents. Based on the expression patterns and functional annotation of the 42 candidate genes, we cloned the full-length gDNA and cDNA sequences of the Ss-inducible chitinase gene set (MlChi family). Phylogenetic tree construction, protein interaction network prediction, and gene expression analysis revealed their special roles in response to Ss infection. In prokaryotic expression, their protein products were all in the form of an inclusion body. Our results will help in the understanding of the molecular basis of Ss-resistance in M. laevigata, and the isolated MlChi genes are candidates for the improvement in plant Ss-resistance via biotechnology.