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1.
J Integr Plant Biol ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695649

RESUMO

Cultivating high-yield wheat under limited water resources is crucial for sustainable agriculture in semiarid regions. Amid water scarcity, plants activate drought response signaling, yet the delicate balance between drought tolerance and development remains unclear. Through genome-wide association studies and transcriptome profiling, we identified a wheat atypical basic helix-loop-helix (bHLH) transcription factor (TF), TabHLH27-A1, as a promising quantitative trait locus candidate for both relative root dry weight and spikelet number per spike in wheat. TabHLH27-A1/B1/D1 knock-out reduced wheat drought tolerance, yield, and water use efficiency (WUE). TabHLH27-A1 exhibited rapid induction with polyethylene glycol (PEG) treatment, gradually declining over days. It activated stress response genes such as TaCBL8-B1 and TaCPI2-A1 while inhibiting root growth genes like TaSH15-B1 and TaWRKY70-B1 under short-term PEG stimulus. The distinct transcriptional regulation of TabHLH27-A1 involved diverse interacting factors such as TaABI3-D1 and TabZIP62-D1. Natural variations of TabHLH27-A1 influence its transcriptional responses to drought stress, with TabHLH27-A1Hap-II associated with stronger drought tolerance, larger root system, more spikelets, and higher WUE in wheat. Significantly, the excellent TabHLH27-A1Hap-II was selected during the breeding process in China, and introgression of TabHLH27-A1Hap-II allele improved drought tolerance and grain yield, especially under water-limited conditions. Our study highlights TabHLH27-A1's role in balancing root growth and drought tolerance, providing a genetic manipulation locus for enhancing WUE in wheat.

2.
J Agric Food Chem ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598771

RESUMO

Intramuscular fat (IMF) plays a crucial role in enhancing meat quality, enriching meat flavor, and overall improving palatability. In this study, Single-cell RNA sequencing was employed to analyze the longissimus dorsi (LD) obtained from Guangdong small-ear spotted pigs (GDSS, with high IMF) and Yorkshire pigs (YK, with low IMF). GDSS had significantly more Fibro/Adipogenic Progenitor (FAPs), in which the CD9 negative FAPs (FAPCD9-) having adipogenic potential, as demonstrated by in vitro assays using cells originated from mouse muscle. On the other hand, Yorkshire had more fibro-inflammatory progenitors (FIPs, marked with FAPCD9+), presenting higher expression of the FBN1-Integrin α5ß1. FBN1-Integrin α5ß1 could inhibit insulin signaling in FAPCD9-, suppressing adipogenic differentiation. Our results demonstrated that fat-type pigs possess a greater number of FAPCD9-, which are the exclusive cells in muscle capable of differentiating into adipocytes. Moreover, lean-type pigs exhibit higher expression of FBN1-Integrin α5ß1 axis, which inhibits adipocyte differentiation. These results appropriately explain the observed higher IMF content in fat-type pigs.

3.
Plant Commun ; : 100850, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38409782

RESUMO

After germination in the dark, plants produce a shoot apical hook and closed cotyledons to protect the quiescent shoot apical meristem (SAM), which is critical for seedling survival during skotomorphogenesis. The factors that coordinate these processes, particularly SAM repression, remain enigmatic. Plant cuticles, multilayered structures of lipid components on the outermost surface of the aerial epidermis of all land plants, provide protection against desiccation and external environmental stresses. Whether and how cuticles regulate plant development are still unclear. Here, we demonstrate that mutants of BODYGUARD1 (BDG1) and long-chain acyl-CoA synthetase2 (LACS2), key genes involved in cutin biosynthesis, produce a short hypocotyl with an opened apical hook and cotyledons in which the SAM is activated during skotomorphogenesis. Light signaling represses expression of BDG1 and LACS2, as well as cutin biosynthesis. Transcriptome analysis revealed that cuticles are critical for skotomorphogenesis, particularly for the development and function of chloroplasts. Genetic and molecular analyses showed that decreased HOOKLESS1 expression results in apical hook opening in the mutants. When hypoxia-induced expression of LITTLE ZIPPER2 at the SAM promotes organ initiation in the mutants, the de-repressed expression of cell-cycle genes and the cytokinin response induce the growth of true leaves. Our results reveal previously unrecognized developmental functions of the plant cuticle during skotomorphogenesis and demonstrate a mechanism by which light initiates photomorphogenesis through dynamic regulation of cuticle synthesis to induce coordinated and systemic changes in organ development and growth during the skotomorphogenesis-to-photomorphogenesis transition.

4.
Hortic Res ; 11(2): uhad292, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38414837

RESUMO

Artemisinin, also known as 'Qinghaosu', is a chemically sesquiterpene lactone containing an endoperoxide bridge. Due to the high activity to kill Plasmodium parasites, artemisinin and its derivatives have continuously served as the foundation for antimalarial therapies. Natural artemisinin is unique to the traditional Chinese medicinal plant Artemisia annua L., and its content in this plant is low. This has motivated the synthesis of this bioactive compound using yeast, tobacco, and Physcomitrium patens systems. However, the artemisinin production in these heterologous hosts is low and cannot fulfil its increasing clinical demand. Therefore, A. annua plants remain the major source of this bioactive component. Recently, the transcriptional regulatory networks related to artemisinin biosynthesis and glandular trichome formation have been extensively studied in A. annua. Various strategies including (i) enhancing the metabolic flux in artemisinin biosynthetic pathway; (ii) blocking competition branch pathways; (iii) using transcription factors (TFs); (iv) increasing peltate glandular secretory trichome (GST) density; (v) applying exogenous factors; and (vi) phytohormones have been used to improve artemisinin yields. Here we summarize recent scientific advances and achievements in artemisinin metabolic engineering, and discuss prospects in the development of high-artemisinin yielding A. annua varieties. This review provides new insights into revealing the transcriptional regulatory networks of other high-value plant-derived natural compounds (e.g., taxol, vinblastine, and camptothecin), as well as glandular trichome formation. It is also helpful for the researchers who intend to promote natural compounds production in other plants species.

5.
J Colloid Interface Sci ; 662: 333-341, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38354560

RESUMO

It is significant to tailor multifunctional electrode materials for storing sustainable energy in lithium-sulfur (Li-S) batteries and converting intermittent solar energy into H2, facilitated by electricity. In this context, COF-1@CNT obtained through interfacial interaction fulfilled both requisites via post-functionalization. Upon integrating COF-1@CNT with S as the cathode for Li-S batteries, the system exhibited an initial discharge capacity of 1360 mAh g-1. Subsequently, it maintained a sustained actual capacity even after undergoing 200 charge-discharge cycles at 0.5C. The performance improvement was attributed to the optimized conductivity due to the addition of carbon nanotubes (CNTs). Furthermore, the synergistic interaction between the nitrogen of COF-1 and lithium mitigated the shuttle effect in Li-S batteries. In the modified three-electrode electrolytic cell system, COF-1@CNT-Ru produced by COF-1@CNT with RuCl3 showed better electrochemical reactivity for photothermal-assisted hydrogen evolution reaction (HER). This effect was demonstrated by reducing the overpotential to 140 mV relative to the no-photothermal condition (180 mV) at a current density of 10 mA cm-2. This study marked the first simultaneous application of covalent organic frameworks (COFs) based materials in Li-S batteries and photothermal-assisted electrocatalysts. The modified electrocatalytic system held promise as a novel avenue for exploring solar thermal energy utilization.

6.
Nat Commun ; 14(1): 8238, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38086830

RESUMO

The breeding of crops with improved nitrogen use efficiency (NUE) is crucial for sustainable agriculture, but the involvement of epigenetic modifications remains unexplored. Here, we analyze the chromatin landscapes of two wheat cultivars (KN9204 and J411) that differ in NUE under varied nitrogen conditions. The expression of nitrogen metabolism genes is closely linked to variation in histone modification instead of differences in DNA sequence. Epigenetic modifications exhibit clear cultivar-specificity, which likely contributes to distinct agronomic traits. Additionally, low nitrogen (LN) induces H3K27ac and H3K27me3 to significantly enhance root growth in KN9204, while remarkably inducing NRT2 in J411. Evidence from histone deacetylase inhibitor treatment and transgenic plants with loss function of H3K27me3 methyltransferase shows that changes in epigenetic modifications could alter the strategy preference for root development or nitrogen uptake in response to LN. Here, we show the importance of epigenetic regulation in mediating cultivar-specific adaptation to LN in wheat.


Assuntos
Nitrogênio , Triticum , Triticum/metabolismo , Nitrogênio/metabolismo , Epigênese Genética , Histonas/genética , Histonas/metabolismo , Melhoramento Vegetal
7.
Inorg Chem ; 62(49): 20279-20287, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38032042

RESUMO

Comprehensive understanding of substituent groups located on the pore surface of metal-organic frameworks (which we call substituent engineering herein) can help to promote gas adsorption and catalytic performance through ligand functionalization. In this work, pore-space-partitioned metal-organic frameworks (PSP MOFs) were selected as a platform to evaluate the effect of organic functional groups on CO2 adsorption, separation, and catalytic conversion. Twelve partitioned acs metal-organic frameworks (pacs-MOFs, named SNNU-25-Rn here) containing different functional groups were synthesized, which can be classified into electron-donor groups (-OH, -NH2, -CH3, and -OCH3) and electron-acceptor groups (-NO2, -F, -Cl, and -Br). The experimental results showed that SNNU-25-Rn with electron donors usually perform better than those with electron acceptors for the comprehensive utilization of CO2. The CO2 uptake of the 12 SNNU-25-Rn MOFs ranged from 30.9 to 183.6 cm3 g-1 at 273 K and 1 bar, depending on the organic functional groups. In particular, SNNU-25-OH showed the highest CO2 adsorption, SNNU-25-CH3 had the highest IAST of CO2/CH4 (36.1), and SNNU-25-(OH)2 showed the best catalytic activity for the CO2 cycloaddition reaction. The -OH functionalized MOFs with excellent performance may be attributed to the Lewis acid-base and hydrogen-bonding interactions between -OH groups and the CO2 molecules. This work modulated the effect of the microenvironment of MOFs on CO2 adsorption, separation, and catalysis in terms of substituents, providing valuable information for the precise design of porous MOFs with a comprehensive utilization of CO2.

8.
Int J Biol Macromol ; 253(Pt 6): 127345, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37820909

RESUMO

Artemisia annua, a member of the Asteraceae family, remains the primary source of artemisinin. However, the artemisinin content in the existing varieties of this plant is very low. In this study, we found that the environmental factors light and phytohormone abscisic acid (ABA) could synergistically promote the expression of artemisinin biosynthetic genes. Notably, the increased expression levels of those genes regulated by ABA depended on light. Gene expression analysis found that AaABI5, a transcription factor belonging to the basic leucine zipper (bZIP) family, was inducible by the light and ABA treatment. Analysis of AaABI5-overexpressing and -suppressing lines suggested that AaABI5 could enhance artemisinin biosynthesis and activate the expression of four core biosynthetic genes. In addition, the key regulator of light-induced artemisinin biosynthesis, AaHY5, could bind to the promoter of AaABI5 and activate its expression. In conclusion, our results demonstrated that AaABI5 acts as an important molecular junction for the synergistic promotion of artemisinin biosynthesis by light and ABA signals, which provides a candidate gene for developing new germplasms of high-quality A. annua.


Assuntos
Antimaláricos , Artemisia annua , Artemisininas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Antimaláricos/farmacologia , Artemisia annua/genética , Artemisia annua/metabolismo , Ácido Abscísico/metabolismo , Artemisininas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
9.
Inorg Chem ; 62(37): 15195-15205, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37656912

RESUMO

Metal-organic frameworks (MOFs) have attracted extensive attention in methane (CH4) purification and storage. Specially, multinuclear cluster-based MOFs usually have prominent performance because of large cluster size and abundant open metal sites. However, compared to diverse combinations of organic linkers, one MOF with two or more multinuclear clusters is difficult to achieve. In this paper, we demonstrate a mixed multinuclear cluster strategy, which successfully led to three new heterometallic MOFs (SNNU-328-330) with the same common H3TATB [2,4,6-tris(4-carboxyphenyl)-1,3,5-triazine] tritopic linker and six types of multinuclear clusters ([YCd(COO)4(µ2-H2O)], [YCd2(COO)8], [In3(COO)6(µ3-OH)], [In3Eu2(COO)9(µ3-OH)3(µ4-O)], [Y9(COO)12(µ3-OH)14] and [Y2Cd8(COO)16(µ2-H2O)4(µ3-OH)8]). Three MOF adsorbents all show great potentials to remove the impurities (CO2 and C2-hydrocarbons) in natural gas and show prominent high-pressure methane storage capacity. Among them, the ideal adsorbed solution theory separation ratios of equimolar C2H2/CH4, C2H4/CH4, C2H6/CH4, and CO2/CH4 at 298 K for SNNU-328 reach to 29.7-16.0, 19.1-8.2, 33.2-10.3, and 74.3-8.5, which have surpassed many famous MOF adsorbents. Dynamic breakthrough experiments conducted at 273 and 298 K showed that SNNU-330 can separate CH4 from C2H2/CH4, C2H4/CH4, C2H6/CH4, and CO2/CH4 mixtures with the breakthrough interval times of about 48.2, 17.9, 37.2, and 17.1 min g-1 (273 K, 1 bar, v/v = 50/50, 2 mL min-1), respectively. Remarkably, SNNU-329 exhibits extremely high methane storage performance at 298 K with the total uptake and working capacity of 192 cm3 cm-3 (95 bar) and 171 cm3 cm-3 (65 bar) due to the synergistic effects of high surface area, suitable pore sizes, and multiple open metal sites.

10.
J Exp Bot ; 74(18): 5441-5457, 2023 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-37402253

RESUMO

Transcriptional regulation is crucial to control of gene expression. Both spatio-temporal expression patterns and expression levels of genes are determined by the interaction between cis-acting elements and trans-acting factors. Numerous studies have focused on the trans-acting factors that mediate transcriptional regulatory networks. However, cis-acting elements, such as enhancers, silencers, transposons, and natural variations in the genome, are also vital for gene expression regulation and could be utilized by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing to improve crop quality and yield. In this review, we discuss current understanding of cis-element-mediated transcriptional regulation in major crops, including rice (Oryza sativa), wheat (Triticum aestivum), and maize (Zea mays), as well as the latest advancements in gene editing techniques and their applications in crops to highlight prospective strategies for crop breeding.


Assuntos
Edição de Genes , Oryza , Edição de Genes/métodos , Sistemas CRISPR-Cas , Estudos Prospectivos , Genoma de Planta/genética , Melhoramento Vegetal , Produtos Agrícolas/genética , Regulação da Expressão Gênica , Oryza/genética , Transativadores/genética
11.
J Colloid Interface Sci ; 650(Pt B): 1466-1475, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37481784

RESUMO

It is worthwhile to explore and develop multifunctional composites with unique advantages for energy conversion and utilization. Post-synthetic modification (PSM) strategies can endow novel properties to already excellent covalent organic frameworks (COFs). In this study, we prepared a range of COF-based composites via a multi-step PSM strategy. COF-Ph-OH was acquired by demethylation between anhydrous BBr3 and - OMe, and then, M@COF-Ph-OH was further obtained by forming the N - M - O structure. COF-Ph-OH exhibited a 2e--dominated oxygen reduction reaction (ORR) pathway with high H2O2 selectivity, while M@COF-Ph-OH exhibited a 4e--dominated ORR pathway with low H2O2 selectivity, which was due to the introduction of a metal salt with a d electron structure that facilitated the acquisition of electrons and changed the adsorption energy of the reaction intermediate (*OOH). It was proven that the d electron structure was effective at regulating the reaction pathway of the electrocatalytic ORR. Moreover, Co@COF-Ph-OH showed better 4e- ORR properties than Fe@COF-Ph-OH and Ni@COF-Ph-OH. In addition, compared with the other sulfur-impregnated COF-based composites examined in this study, S-Co@COF-Ph-OH had a larger initial capacity, a weaker impedance, and a stronger cycling durability in Li-S batteries, which was attributed to the unique porous structure ensuring high sulfur utilization, the loaded cobalt accelerating LiPS electrostatic adsorption and promoting LiPS catalytic conversion, and the benzoquinoline ring structure being ultra-stable. This work offers not only a rational and feasible strategy for the synthesis of multifunctional COF-based composites, but also promotes their application in electrochemistry.

12.
J Colloid Interface Sci ; 645: 146-153, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37148680

RESUMO

Covalent organic frameworks (COFs) are considered as a class of potential candidates for energy storage and catalysis. In this work, a COF containing sulfonic groups was prepared to be a modified separator in lithium-sulfur batteries (LSBs). Benefiting from the charged sulfonic groups, the COF-SO3 cell exhibited higher ionic conductivity (1.83 mS⋅cm-1). Moreover, the modified COF-SO3 separator not only inhibited the shuttle of polysulfide but also promoted Li+ diffusion, thanks to the electrostatic interaction. The COF-SO3 cell also showed excellent electrochemical performance that the initial specific capacity of the battery was 890 mA h g-1 at 0.5 C and demonstrated 631 mA h g-1 after 200 cycles. In addition, COF-SO3 with satisfactory electrical conductivity was also used as an electrocatalyst toward oxygen evolution reaction (OER) via cation-exchange strategy. The electrocatalyst COF-SO3@FeNi possessed a low overpotential (350 mV at 10 mA cm-2) in an alkaline aqueous electrolyte. Furthermore, COF-SO3@FeNi exhibited exceptional stability, and the overpotential increased about 11 mV at a current density of 10 mA cm-2 after 1000 cycles. This work facilitates the application of versatile COFs in the electrochemistry field.

13.
J Clin Lab Anal ; 37(8): e24896, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37198144

RESUMO

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is a multifactorial disease, and its etiology is still unknown. SSNHL may be caused by environmental factors and genetic changes. PCDH15 is associated with susceptibility to hearing loss. The relationship between PCDH15 and SSNHL remains unknown. METHODS: In this study, the potential association between PCDH15 polymorphism and SSNHL in Chinese population was evaluated. Two single nucleotide polymorphisms PCDH15-rs7095441 and rs11004085 in 195 SSNHL patients and 182 healthy controls were determined by TaqMan technology. RESULTS: In Chinese population, the TT genotype and T allele of rs7095441 are associated with increased susceptibility to SSNHL. The relationships between rs7095441 and the degree of hearing loss were analyzed, and TT genotype increased the risk of hearing loss. Among SSNHL patients, patients with TT genotype of rs7095441 have an increased risk of vertigo. CONCLUSION: This study found that the TT genotype of SNP rs7095441 can increase the risk of SSNHL in Chinese population.


Assuntos
Surdez , Perda Auditiva Neurossensorial , Humanos , População do Leste Asiático , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/genética , Polimorfismo de Nucleotídeo Único/genética , Protocaderinas
15.
Int J Biol Macromol ; 242(Pt 3): 124910, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37217041

RESUMO

Ophiorrhiza pumila, as a folk herb belonging to the Rubiaceae family, has become a potential source of camptothecin (CPT), which is a monoterpenoid indole alkaloid with good antitumor property. However, the camptothecin content in this herb is low, and is far from meeting the increasing clinical demand. Understanding the transcriptional regulation of camptothecin biosynthesis provides an effective strategy for improvement of camptothecin yield. Previous studies have demonstrated several transcription factors that are related to camptothecin biosynthesis, while the functions of HD-ZIP members in O. pumila have not been investigated yet. In this study, 32 OpHD-ZIP transcription factor members were genome-wide identified. Phylogenetic tree showed that these OpHD-ZIP proteins are divided into four subfamilies. Based on the transcriptome data, nine OpHD-ZIP genes were shown to be predominantly expressed in O. pumila roots, which were in line with the camptothecin biosynthetic genes. Co-expression analysis showed that OpHD-ZIP7 and OpHD-ZIP20 were potentially related to the modulation of camptothecin biosynthesis. Dual-luciferase reporter assays (Dual-LUC) showed that both OpHD-ZIP7 and OpHD-ZIP20 could activate the expression of camptothecin biosynthetic genes OpIO and OpTDC. In conclusion, this study offered the promising data for exploring the roles of OpHD-ZIP transcription factors in regulating camptothecin biosynthesis.


Assuntos
Proteínas de Transporte de Cátions , Rubiaceae , Camptotecina , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Filogenia , Proteínas de Transporte de Cátions/genética , Retículo Endoplasmático/metabolismo , Zinco/metabolismo , Rubiaceae/genética
16.
Plant Cell Physiol ; 64(7): 771-785, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37098222

RESUMO

Artemisinin, a sesquiterpene lactone obtained from Artemisia annua, is an essential therapeutic against malaria. YABBY family transcription factor AaYABBY5 is an activator of AaCYP71AV1 (cytochrome P450-dependent hydroxylase) and AaDBR2 (double-bond reductase 2); however, the protein-protein interactions of AaYABBY5, as well as the mechanism of its regulation, have not yet been elucidated. AaWRKY9 protein is a positive regulator of artemisinin biosynthesis that activates AaGSW1 (glandular trichome-specific WRKY1) and AaDBR2 (double-bond reductase 2). In this study, YABBY-WRKY interactions are revealed to indirectly regulate artemisinin production. AaYABBY5 significantly increased the activity of the luciferase (LUC) gene fused to the promoter of AaGSW1. Toward the molecular basis of this regulation, AaYABBY5 interaction with AaWRKY9 protein was found. The combined effectors AaYABBY5 + AaWRKY9 showed synergistic effects toward the activities of AaGSW1 and AaDBR2 promoters, respectively. In AaYABBY5 overexpression plants, the expression of GSW1 was found to be significantly increased when compared to that of AaYABBY5 antisense or control plants. In addition, AaGSW1 was identified as an upstream activator of AaYABBY5. Further, it was found that AaJAZ8, a transcriptional repressor of jasmonate signaling, interacted with AaYABBY5 and attenuated its activity. Co-expression of AaYABBY5 and anti-AaJAZ8 in A. annua increased the activity of AaYABBY5 toward artemisinin biosynthesis. This current study provides the first indication of the molecular basis of regulation of artemisinin biosynthesis through YABBY-WRKY interactions, which are regulated through AaJAZ8. This knowledge presents AaYABBY5 overexpression plants as a powerful genetic resource for artemisinin biosynthesis.


Assuntos
Artemisia annua , Artemisininas , Artemisia annua/genética , Artemisia annua/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regiões Promotoras Genéticas/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Artemisininas/metabolismo
17.
Plant Commun ; 4(4): 100593, 2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-36945776

RESUMO

A better understanding of wheat functional genomics can improve targeted breeding for better agronomic traits and environmental adaptation. However, the lack of gene-indexed mutants and the low transformation efficiency of wheat limit in-depth gene functional studies and genetic manipulation for breeding. In this study, we created a library for KN9204, a popular wheat variety in northern China, with a reference genome, transcriptome, and epigenome of different tissues, using ethyl methyl sulfonate (EMS) mutagenesis. This library contains a vast developmental diversity of critical tissues and transition stages. Exome capture sequencing of 2090 mutant lines using KN9204 genome-designed probes revealed that 98.79% of coding genes had mutations, and each line had an average of 1383 EMS-type SNPs. We identified new allelic variations for crucial agronomic trait-related genes such as Rht-D1, Q, TaTB1, and WFZP. We tested 100 lines with severe mutations in 80 NAC transcription factors (TFs) under drought and salinity stress and identified 13 lines with altered sensitivity. Further analysis of three lines using transcriptome and chromatin accessibility data revealed hundreds of direct NAC targets with altered transcription patterns under salt or drought stress, including SNAC1, DREB2B, CML16, and ZFP182, factors known to respond to abiotic stress. Thus, we have generated and indexed a KN9204 EMS mutant library that can facilitate functional genomics research and offer resources for genetic manipulation of wheat.


Assuntos
Genômica , Triticum , Triticum/genética , Mutação , Mutagênese , Fenótipo
18.
Am J Cancer Res ; 13(1): 161-175, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36777513

RESUMO

The therapeutic management of various HER2-positive malignancies involves the use of HER2-targeted antibody-drug conjugates (ADCs). The primary mechanism of action of ADCs is the release of cytotoxic chemicals, which leads to single- or double-strand DNA breaks and cell death. Since both endogenous and exogenous sources of DNA damage are unavoidable, cells have evolved DNA damage-repair mechanisms. Therefore, combining inhibitors of DNA damage repair and HER2-targeted ADCs may be a practical strategy for treating HER2-positive cancers. Effects of the HER2-targeted ADC, DS-8201, in combination with PARPi (AZD2281), a DNA damage repair inhibitor that targets poly(ADP-ribose) polymerase, and ATRi (BAY1895344), which inhibits the serine/threonine kinase ATR, were determined by assessing cell-growth inhibition, apoptosis and cell-cycle arrest, as well as using in vivo pharmacodynamic studies. Combined use of AZD2281 and BAY1895344 synergistically potentiated the inhibitory effects of DS-8201 on the growth of HER2-positive cancer cells, inducing DNA damage and apoptosis, but had no effect on HER2-negative MDA-MB-231 breast cancer cells. Our data demonstrate that DS-8201 and DNA damage repair inhibitors together have synergistic anticancer effects in NCI-N87 xenograft models, effects that may reflect upregulation of γ-H2AX protein in tumor tissues. Collectively, our results indicate that the combination of DS-8201, BAY1895344, and AZD2281 exerts significant synergistic antitumor activity, suggesting that DNA damage-repair inhibitors in combination with HER2-targeted ADCs is a potential approach for treating HER2-positive malignancies, offering a promising strategy for future clinical applications.

19.
Mol Biol Rep ; 50(4): 3557-3568, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36787056

RESUMO

BACKGROUND: Lung cancer is a high incidence cancer on a worldwide basis and has become a major public health problem. Lung adenocarcinoma (LUAD) makes up approximately half of all lung cancers and is a threat to human health. Long non-coding RNAs (lncRNAs) is an important regulator of the development and progression of lung adenocarcinoma. In this manuscript we examined the role and potential mechanism of lncRNA PCAT6 in the development of LUAD. METHODS AND RESULTS: Differences in lncRNA PCAT6 levels between LUAD samples and normal samples were first explored in the GEPIA database. We found that lncRNA PCAT6 expression was elevated, which was also validated in lung adenocarcinoma tissues and cell lines. Using western blotting, CCK-8, EdU, wound healing and transwell assays, we found that knockdown of lncRNA PCAT6 inhibited EMT, proliferation, migration, and invasion of LUAD cells. We noted a predicted a binding site for lncRNA PCAT6 and miR-545-3p through conducting bioinformatic analyses, and their binding was subsequently verified by a dual-luciferase reporter assay. Rescue experiments confirmed that miR-545-3p inhibitor partially abolished the inhibition function of lncRNA PCAT6 knockdown on LUAD cells. In addition, we predicted the downstream target genes of miR-545-3p and verified them by RT-qPCR. We found that EGFR was reduced in the silence of lncRNA PCAT6 and upregulated after miR-545-3p inhibition. CONCLUSION: This study demonstrates that lncRNA PCAT6 promotes a more aggressive LUAD phenotype by sponging miR-545-3p. This finding may provide new ideas for the treatment of lung cancer.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transição Epitelial-Mesenquimal/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Movimento Celular/genética , Neoplasias Pulmonares/metabolismo , Linhagem Celular Tumoral , Adenocarcinoma/genética , Adenocarcinoma/patologia , Pulmão/metabolismo
20.
Plant Physiol ; 192(2): 1483-1497, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-36810650

RESUMO

Glandular secretory trichomes (GSTs) can secrete and store a variety of specific metabolites. By increasing GST density, valuable metabolites can be enhanced in terms of productivity. However, the comprehensive and detailed regulatory network of GST initiation still needs further investigation. By screening a complementary DNA library derived from young leaves of Artemisia annua, we identified a MADS-box transcription factor, AaSEPALLATA1 (AaSEP1), that positively regulates GST initiation. Overexpression of AaSEP1 in A. annua substantially increased GST density and artemisinin content. The HOMEODOMAIN PROTEIN 1 (AaHD1)-AaMYB16 regulatory network regulates GST initiation via the jasmonate (JA) signaling pathway. In this study, AaSEP1 enhanced the function of AaHD1 activation on downstream GST initiation gene GLANDULAR TRICHOME-SPECIFIC WRKY 2 (AaGSW2) through interaction with AaMYB16. Moreover, AaSEP1 interacted with the JA ZIM-domain 8 (AaJAZ8) and served as an important factor in JA-mediated GST initiation. We also found that AaSEP1 interacted with CONSTITUTIVE PHOTOMORPHOGENIC 1 (AaCOP1), a major repressor of light signaling. In this study, we identified a MADS-box transcription factor that is induced by JA and light signaling and that promotes the initiation of GST in A. annua.


Assuntos
Artemisia annua , Tricomas , Tricomas/genética , Tricomas/metabolismo , Artemisia annua/genética , Artemisia annua/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ciclopentanos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
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