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1.
Mol Cell ; 81(9): 1890-1904.e7, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33657401

RESUMO

O-linked ß-N-acetyl glucosamine (O-GlcNAc) is attached to proteins under glucose-replete conditions; this posttranslational modification results in molecular and physiological changes that affect cell fate. Here we show that posttranslational modification of serine/arginine-rich protein kinase 2 (SRPK2) by O-GlcNAc regulates de novo lipogenesis by regulating pre-mRNA splicing. We found that O-GlcNAc transferase O-GlcNAcylated SRPK2 at a nuclear localization signal (NLS), which triggers binding of SRPK2 to importin α. Consequently, O-GlcNAcylated SRPK2 was imported into the nucleus, where it phosphorylated serine/arginine-rich proteins and promoted splicing of lipogenic pre-mRNAs. We determined that protein nuclear import by O-GlcNAcylation-dependent binding of cargo protein to importin α might be a general mechanism in cells. This work reveals a role of O-GlcNAc in posttranscriptional regulation of de novo lipogenesis, and our findings indicate that importin α is a "reader" of an O-GlcNAcylated NLS.


Assuntos
Neoplasias da Mama/metabolismo , Glucose/metabolismo , Lipogênese , Processamento de Proteína Pós-Traducional , Proteínas Serina-Treonina Quinases/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Neoplasias da Mama/genética , Proliferação de Células , Feminino , Glicosilação , Células HEK293 , Humanos , Células MCF-7 , Camundongos Nus , N-Acetilglucosaminiltransferases/genética , N-Acetilglucosaminiltransferases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Precursores de RNA/genética , Precursores de RNA/metabolismo , Splicing de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Carga Tumoral , alfa Carioferinas/genética , alfa Carioferinas/metabolismo , beta Carioferinas/genética , beta Carioferinas/metabolismo
2.
Mol Cell ; 68(3): 591-604.e5, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29100056

RESUMO

The Hippo pathway is crucial in organ size control and tissue homeostasis, with deregulation leading to cancer. An extracellular nutrition signal, such as glucose, regulates the Hippo pathway activation. However, the mechanisms are still not clear. Here, we found that the Hippo pathway is directly regulated by the hexosamine biosynthesis pathway (HBP) in response to metabolic nutrients. Mechanistically, the core component of Hippo pathway (YAP) is O-GlcNAcylated by O-GlcNAc transferase (OGT) at serine 109. YAP O-GlcNAcylation disrupts its interaction with upstream kinase LATS1, prevents its phosphorylation, and activates its transcriptional activity. And this activation is not dependent on AMPK. We also identified OGT as a YAP-regulated gene that forms a feedback loop. Finally, we confirmed that glucose-induced YAP O-GlcNAcylation and activation promoted tumorigenesis. Together, our data establish a molecular mechanism and functional significance of the HBP in directly linking extracellular glucose signal to the Hippo-YAP pathway and tumorigenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transformação Celular Neoplásica/metabolismo , Glucose/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Neoplasias/enzimologia , Fosfoproteínas/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Regulação Neoplásica da Expressão Gênica , Glicosilação , Células HEK293 , Células HeLa , Humanos , Camundongos Nus , Neoplasias/genética , Neoplasias/patologia , Fosfoproteínas/genética , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Serina , Transdução de Sinais , Fatores de Tempo , Fatores de Transcrição , Transcrição Gênica , Ativação Transcricional , Proteínas de Sinalização YAP
3.
Plant Cell Environ ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747469

RESUMO

Drought, as a primary environmental factor, imposes significant constraints on developmental processes and productivity of plants. PHDs were identified as stress-responsive genes in a wide range of eukaryotes. However, the regulatory mechanisms governing PHD genes in maize under abiotic stress conditions are still largely unknown and require further investigation. Here, we identified a mutant, zmvil2, in the EMS mutant library with a C to T mutation in the exon of the Zm00001d053875 (VIN3-like protein 2, ZmVIL2), resulting in premature termination of protein coding. ZmVIL2 belongs to PHD protein family. Compared to WT, zmvil2 mutant exhibited increased sensitivity to drought stress. Consistently, overexpression of ZmVIL2 enhances drought resistance in maize. Y2H, BiFC, and Co-IP experiments revealed that ZmVIL2 directly interacts with ZmFIP37 (FKBP12-interacting protein of 37). zmfip37 knockout mutants also exhibit decreased drought tolerance. Interestingly, we demonstrated that ZmABF4 directly binds to the ZmVIL2 promoter to enhance its activity in yeast one hybrid (Y1H), electrophoretic mobility shift assay (EMSA) and dual luciferase reporter assays. Therefore, we uncovered a novel model ZmABF4-ZmVIL2/ZmFIP37 that promotes drought tolerance in maize. Overall, these findings have enriched the knowledge of the functions of PHD genes in maize and provides genetic resources for breeding stress-tolerant maize varieties.

4.
Hum Reprod ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38852063

RESUMO

STUDY QUESTION: Does the morphological quality on Day 3 influence the pregnancy outcomes of euploid blastocysts? SUMMARY ANSWER: The morphological quality on Day 3 affects the clinical pregnancy rate (CPR) and live birth rate (LBR) of low-quality euploid blastocysts. WHAT IS KNOWN ALREADY: The morphological grading of Day 3 embryos affects the pregnancy outcome of cleavage-stage embryos and is an excellent indicator to predict embryo development potential. However, it is still unclear whether morphological quality on Day 3 is associated with pregnancy outcomes of the euploid blastocyst. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study comprised 1275 patients who received single euploid blastocyst transfer between January 2016 and August 2021 at a tertiary teaching hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were grouped into two groups according to the morphological grading on Day 3 of transferred blastocysts: high-quality (HQ, including Grades I and II) Day 3 embryos and low-quality (LQ, Grade III) Day 3 embryos. The primary outcomes were CPR and LBR. Interactions of development days (Day 5 and Day 6) and morphological quality (high- and low-quality) of blastocysts with morphological quality of Day 3 embryos on pregnancy outcomes were tested in the stratified analysis and logistic regression models. The multivariate logistic regression analysis was conducted to investigate the independent effect of the morphological quality of Day 3 embryos on pregnancy outcomes after adjusting for potentially confounding factors. MAIN RESULTS AND THE ROLE OF CHANCE: The CPR and LBR of the HQ Day 3 embryos group were statistically higher than those of the LQ Day 3 embryos group (CPR: 59.73% versus 49.70%, respectively, P = 0.015; LBR: 49.73% versus 41.21%, respectively, P = 0.041). The development days of blastocysts did not exhibit a multiplicative interaction with the morphological quality of Day 3 embryos on the CPR (P for interaction = 0.648) and LBR (P for interaction = 0.925). The morphological quality of blastocysts exhibits a multiplicative interaction with the morphological quality of Day 3 embryos on the CPR (P for interaction = 0.020) and LBR (P for interaction = 0.012). After adjusting for potential confounders, the HQ Day 3 embryo group was positively associated with the CPR (adjusted odds ratio (aOR): 2.10, 95% CI: 1.31-3.36, P = 0.002) and LBR (aOR: 1.97, 95% CI: 1.20-3.25, P = 0.008) of LQ blastocysts. However, the morphological quality on Day 3 was not significantly associated with the CPR (aOR: 0.95, 95% CI: 0.58-1.55, P = 0.835) and LBR (aOR: 0.86, 95% CI: 0.53-1.40, P = 0.550) of HQ blastocysts. LIMITATIONS, REASONS FOR CAUTION: Selection and confounding bias introduced by the retrospective design cannot be completely eliminated in this study, although multivariable logistic analysis was conducted to adjust for potential confounders. Also, some subgroups had small sample sizes, which may reduce statistical power. Moreover, participants in our study only received single euploid blastocyst transfer, and whether the results could apply to blastocysts with unknown ploidy status is unclear. WIDER IMPLICATIONS OF THE FINDINGS: This study found that the morphological quality on Day 3 was significantly associated with the CPR and LBR of LQ blastocysts; Therefore, when only LQ euploid blastocysts are available for transfer, blastocysts derived from HQ Day 3 embryos are recommended. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

5.
Environ Res ; 251(Pt 2): 118747, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38527717

RESUMO

A composite material, cow dung-doped sludge biochar (Zn@SBC-CD), was synthesized by one-step pyrolysis using ZnCl2 as an activating agent and applied to a catalytic ozonation process (COP) for methylene blue (MB) removal. SEM, XRD, FTIR, XPS and BET analyses were performed to characterize the biochar (BC) catalysts. Zn@SBC-CD had high graphitization degree, abundant active sites and uniform distribution of Zn on its surface. Complete removal of MB was achieved within 10 min, with a removal rate much higher than that of ozone alone (32.4%), implying the excellent ozone activation performance of Zn@SBC-CD. The influence of experimental parameters on MB removal efficiency was examined. Under the optimum conditions in terms of ozone dose 0.04 mg/mL, catalyst dose 400 mg/L and pH 6.0, COD was completely removed after 20 min. Electron paramagnetic resonance (EPR) analysis revealed radical and non-radical pathways were involved in MB degradation. The Zn@SBC-CD/O3 system generated superoxide anion radicals (•O2-), which were the main active species for MB removal, through adsorption, transformation, and transfer, Furthermore, Zn@SBC-CD exhibited good reusability and stability in cycling experiments. This study provides a novel approach for the utilization of cow dung and sludge in synthesis of functional biocatalysts and application in organic wastewater treatment.


Assuntos
Carvão Vegetal , Grafite , Ozônio , Ozônio/química , Carvão Vegetal/química , Animais , Bovinos , Catálise , Grafite/química , Esgotos/química , Azul de Metileno/química , Radicais Livres/química , Poluentes Químicos da Água/química , Esterco/análise
6.
Plant Cell Rep ; 43(4): 101, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498195

RESUMO

KEY MESSAGE: Over expression of MsSPL12 improved alfalfa salt tolerance by reducing Na+ accumulation and increasing antioxidant enzyme activity and regulating down-stream gene expression. Improvement of salt tolerance is one of the major goals in alfalfa breeding. Here, we demonstrated that MsSPL12, an alfalfa transcription factor gene highly expressed in the stem cells, plays a positive role in alfalfa salt tolerance. MsSPL12 is localized in the nucleus and shows transcriptional activity in the presence of its C-terminus. To investigate MsSPL12 function in plant response to salt stress, we generated transgenic plants overexpressing either MsSPL12 or a chimeric MsSPL12-SRDX gene that represses the function of MsSPL12 by using the Chimeric REpressor gene-Silencing Technology (CRES-T), and observed that overexpression of MsSPL12 increased the salt tolerance of alfalfa transgenic plants associated with an increase in K+/Na+ ratio and relative water content (RWC) under salt stress treatment, but a reduction in electrolyte leakage (EL), reactive oxygen species (ROS), malondialdehyde (MDA), and proline (Pro) compared to wild type (WT) plants. However, transgenic plants overexpressing MsSPL12-SRDX showed an inhibited plant growth and a reduced salt tolerance. RNA-sequencing and quantitative real-time PCR analyses revealed that MsSPL12 affected the expression of plant abiotic resistance-related genes in multiple physiological pathways. The potential MsSPL12-mediated regulatory pathways based on the differentially expressed genes between the MsSPL12 overexpression transgenics and WT controls were predicted. In summary, our study proves that MsSPL12 is a positive regulator in alfalfa salt tolerance and can be used as a new candidate for manipulation to develop forage crops with enhanced salt tolerance.


Assuntos
Medicago sativa , Tolerância ao Sal , Tolerância ao Sal/genética , Medicago sativa/genética , Medicago sativa/metabolismo , Melhoramento Vegetal , Plantas Geneticamente Modificadas/genética , Genes de Plantas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
7.
Anal Chem ; 95(30): 11326-11334, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37409763

RESUMO

Single-cell omics is critical in revealing population heterogeneity, discovering unique features of individual cells, and identifying minority subpopulations of interest. As one of the major post-translational modifications, protein N-glycosylation plays crucial roles in various important biological processes. Elucidation of the variation in N-glycosylation patterns at single-cell resolution may largely facilitate the understanding of their key roles in the tumor microenvironment and immune therapy. However, comprehensive N-glycoproteome profiling for single cells has not been achieved due to the extremely limited sample amount and incompatibility with the available enrichment strategies. Here, we have developed an isobaric labeling-based carrier strategy for highly sensitive intact N-glycopeptide profiling for single cells or a small number of rare cells without enrichment. Isobaric labeling has unique multiplexing properties, by which the "total" signal from all channels triggers MS/MS fragmentation for N-glycopeptide identification, while the reporter ions provide quantitative information. In our strategy, a carrier channel using N-glycopeptides obtained from bulk-cell samples significantly improved the "total" signal of N-glycopeptides and, therefore, promoted the first quantitative analysis of averagely 260 N-glycopeptides from single HeLa cells. We further applied this strategy to study the regional heterogeneity of N-glycosylation of microglia in mouse brain and discovered region-specific N-glycoproteome patterns and cell subtypes. In conclusion, the glycocarrier strategy provides an attractive solution for sensitive and quantitative N-glycopeptide profiling of single/rare cells that cannot be enriched by traditional workflows.


Assuntos
Glicopeptídeos , Espectrometria de Massas em Tandem , Humanos , Animais , Camundongos , Glicopeptídeos/análise , Células HeLa , Glicosilação , Processamento de Proteína Pós-Traducional , Proteoma/análise
8.
BMC Plant Biol ; 23(1): 301, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280506

RESUMO

BACKGROUND: Medicago sativa is the most important forage world widely, and is characterized by high quality and large biomass. While abiotic factors such as salt stress can negatively impact the growth and productivity of alfalfa. Maintaining Na+/K+ homeostasis in the cytoplasm helps reduce cell damage and nutritional deprivation, which increases a salt-tolerance of plant. Teosinte Branched1/ Cycloidea/ Proliferating cell factors (TCP) family genes, a group of plant-specific transcription factors (TFs), involved in regulating plant growth and development and abiotic stresses. Recent studies have shown TCPs control the Na+/K+ concentration of plants during salt stress. In order to improve alfalfa salt tolerance, it is important to identify alfalfa TCP genes and investigate if and how they regulate alfalfa Na+/K+ homeostasis. RESULTS: Seventy-one MsTCPs including 23 non-redundant TCP genes were identified in the database of alfalfa genome (C.V XinJiangDaYe), they were classified into class I PCF (37 members) and class II: CIN (28 members) and CYC/TB1 (9 members). Their distribution on chromosome were unequally. MsTCPs belonging to PCF were expressed specifically in different organs without regularity, which belonging to CIN class were mainly expressed in mature leaves. MsTCPs belongs to CYC/TB1 clade had the highest expression level at meristem. Cis-elements in the promoter of MsTCPs were also predicted, the results indicated that most of the MsTCPs will be induced by phytohormone and stress treatments, especially by ABA-related stimulus including salinity stress. We found 20 out of 23 MsTCPs were up-regulated in 200 mM NaCl treatment, and MsTCP3/14/15/18 were significantly induced by 10 µM KCl, a K+ deficiency treatment. Fourteen non-redundant MsTCPs contained miR319 target site, 11 of them were upregulated in MIM319 transgenic alfalfa, and among them four (MsTCP3/4/10A/B) genes were directly degraded by miR319. MIM319 transgene alfalfa plants showed a salt sensitive phenotype, which caused by a lower content of potassium in alfalfa at least partly. The expression of potassium transported related genes showed significantly higher expression in MIM319 plants. CONCLUSIONS: We systematically analyzes the MsTCP gene family at a genome-wide level and reported that miR319-TCPs model played a function in K+ up-taking and/ or transportation especially in salt stress. The study provide valuable information for future study of TCP genes in alfalfa and supplies candidate genes for salt-tolerance alfalfa molecular-assisted breeding.


Assuntos
Genes de Plantas , Medicago sativa , Medicago sativa/metabolismo , Genes de Plantas/genética , Tolerância ao Sal/genética , Plantas Geneticamente Modificadas/genética , Potássio/metabolismo , Homeostase , Regulação da Expressão Gênica de Plantas
9.
Environ Sci Technol ; 57(30): 11075-11083, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37471467

RESUMO

Acid deposition in China has been declining since the 2000s. While this may help mitigate acidification in forest soils and water, little is known about the recovery of soils and water from previous severe acidification in tropical China. Here, we assessed the chemistry of mineral soils, water, and acid gases (SO2 and NOx) from three successional forest types in tropical China from 2000 to 2022. Our results showed that soil pH increased synchronously from 3.9 (2000-2015) to 4.2 (2016-2022) across all three forest types, with exchangeable acid initially decreasing and thereafter stabilizing. Surface and ground water pH also gradually increased throughout the monitoring period. Soil pH recovery was stronger in the primary than in the planted forest. However, soil pH recovery lagged behind the increase in rainfall pH by approximately a decade. The recovery of soil pH was likely related to the positive effects of the dissolution of Al/Fe-hydroxysulfate mineral and subsequent sulfur desorption on soil acid-neutralizing capacity, increased soil organic matter, and climate warming, but was likely moderated by increased exchangeable aluminum and potentially proton-producing hydroxysulfate mineral dissolution that caused the lagged soil pH recovery. Surface and ground water pH recovery was attributed to increased water acid-neutralizing capacity. Our study reports the potential for the recovery of acidified soil and water following decreased acid deposition and provides new insights into the functional recovery of acid-sensitive forests.

10.
Plant Cell Rep ; 42(4): 805-819, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36757447

RESUMO

KEY MESSAGE: Sequestering microRNA396 by overexpression of MIM396 enhanced alfalfa resistance to Spodoptera litura larvae, which may be due to increased lignin content and enhanced low-molecular weight flavonoids and glucosinolates biosynthesis. Alfalfa (Medicago sativa), the most important leguminous forage crop, suffers from the outbreak of defoliator insects, especially Spodoptera litura, resulting in heavy losses in yield and forage quality. Here, we found that the expression of alfalfa microRNA396 (miR396) precursor genes and mature miR396 was significantly up-regulated in wounding treatment that simulates feeding injury by defoliator insects. To verify the function of miR396 in alfalfa resistance to insect, we generated MIM396 transgenic alfalfa plants with significantly down-regulated miR396 expression by Agrobacterium-mediated genetic transformation. The MIM396 transgenic alfalfa plants exhibited improved resistance to Spodoptera litura larvae with increased lignin content but decreased JA accumulation. Most of the miR396 putative target GRF genes were up-regulated in MIM396 transgenic lines, and responded to the wounding treatment. By RNA sequencing analysis, we found that the differentially expressed genes related to insect resistance between WT and MIM396 transgenic plants mainly clustered in biosynthesis pathways in lignin, flavonoids and glucosinolates. In addition to the phenotype of enhanced insect resistance, MIM396 transgenic plants also displayed reduced biomass yield and forage quality. Our results broaden the function of miR396 in alfalfa and provide genetic resources for studying alfalfa insect resistance.


Assuntos
Herbivoria , Medicago sativa , Plantas Geneticamente Modificadas , Spodoptera , Animais , Flavonoides , Regulação da Expressão Gênica de Plantas , Glucosinolatos , Lignina , Medicago sativa/genética , MicroRNAs/genética , Plantas Geneticamente Modificadas/genética
11.
Sensors (Basel) ; 23(17)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37688018

RESUMO

Temporal action detection is a very important and challenging task in the field of video understanding, especially for datasets with significant differences in action duration. The temporal relationships between the action instances contained in these datasets are very complex. For such videos, it is necessary to capture information with a richer temporal distribution as much as possible. In this paper, we propose a dual-stream model that can model contextual information at multiple temporal scales. First, the input video is divided into two resolution streams, followed by a Multi-Resolution Context Aggregation module to capture multi-scale temporal information. Additionally, an Information Enhancement module is added after the high-resolution input stream to model both long-range and short-range contexts. Finally, the outputs of the two modules are merged to obtain features with rich temporal information for action localization and classification. We conducted experiments on three datasets to evaluate the proposed approach. On ActivityNet-v1.3, an average mAP (mean Average Precision) of 32.83% was obtained. On Charades, the best performance was obtained, with an average mAP of 27.3%. On TSU (Toyota Smarthome Untrimmed), an average mAP of 33.1% was achieved.

12.
Sensors (Basel) ; 23(12)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37420580

RESUMO

Graph convolutional networks are widely used in skeleton-based action recognition because of their good fitting ability to non-Euclidean data. While conventional multi-scale temporal convolution uses several fixed-size convolution kernels or dilation rates at each layer of the network, we argue that different layers and datasets require different receptive fields. We use multi-scale adaptive convolution kernels and dilation rates to optimize traditional multi-scale temporal convolution with a simple and effective self attention mechanism, allowing different network layers to adaptively select convolution kernels of different sizes and dilation rates instead of being fixed and unchanged. Besides, the effective receptive field of the simple residual connection is not large, and there is a great deal of redundancy in the deep residual network, which will lead to the loss of context when aggregating spatio-temporal information. This article introduces a feature fusion mechanism that replaces the residual connection between initial features and temporal module outputs, effectively solving the problems of context aggregation and initial feature fusion. We propose a multi-modality adaptive feature fusion framework (MMAFF) to simultaneously increase the receptive field in both spatial and temporal dimensions. Concretely, we input the features extracted by the spatial module into the adaptive temporal fusion module to simultaneously extract multi-scale skeleton features in both spatial and temporal parts. In addition, based on the current multi-stream approach, we use the limb stream to uniformly process correlated data from multiple modalities. Extensive experiments show that our model obtains competitive results with state-of-the-art methods on the NTU-RGB+D 60 and NTU-RGB+D 120 datasets.


Assuntos
Sistema Musculoesquelético , Esqueleto , Reconhecimento Psicológico , Algoritmos , Extremidades
13.
J Am Chem Soc ; 144(10): 4289-4293, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35138101

RESUMO

O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. O-GlcNAc is catalyzed solely by O-GlcNAc transferase (OGT). The study of protein O-GlcNAc function is limited by the lack of tools to control OGT activity with spatiotemporal resolution in cells. Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. This enables the expression of a transiently inactivated form of OGT, which can be rapidly reactivated by photo-decaging. We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. We further apply this activation strategy to control the morphological contraction of fibroblasts. Furthermore, we achieved spatial activation of OGT activity predominantly in the cytosol. Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function.


Assuntos
Lisina , N-Acetilglucosaminiltransferases , Acetilglucosamina/metabolismo , Glicoproteínas/metabolismo , Lisina/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Processamento de Proteína Pós-Traducional , Proteômica
14.
Anal Chem ; 94(43): 14956-14964, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36264706

RESUMO

Blood is one of the most important clinical samples for protein biomarker discovery, as it provides rich physiological and pathological information and is easy to obtain with low invasiveness. However, the discovery of protein biomarkers in the blood by mass spectrometry (MS)-based proteomic strategies has been shown to be highly challenging due to the particularly large concentration range of proteins and the strong interference by the high-abundant proteins in the blood. Therefore, developing sensitive methods for low-abundant biomarker protein identification is a key issue that has received great attention. Here, we report the synthesis and characterization of surface-functionalized magnetic molybdenum disulfide (MoS2) for the large-scale adsorption of low-abundant plasma proteins and deep profiling by MS. MoS2 nanomaterials resulted in the coverage of more than 3400 proteins (including a single-peptide hit) in a single LC-MS analysis without peptide prefractionation using pooled plasma samples, which were five times more than those obtained by the direct analysis of the plasma proteome. A detection limit in the low ng L-1 range was obtained, which is rare compared with previous reports.


Assuntos
Nanoestruturas , Proteoma , Humanos , Proteoma/análise , Proteômica/métodos , Molibdênio , Adsorção , Biomarcadores , Peptídeos
15.
BMC Ophthalmol ; 22(1): 2, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980022

RESUMO

BACKGROUND: Implantable Collamer lens (ICL) vaulting is one of the most important parameters for the safety, aqueous humor circulation, and lens transparency after ICL implantation. This study aimed to investigate the factors associated with the actual vaulting after refractive EVO-ICL surgery. METHODS: This retrospective study included patients who underwent EVO-ICL surgery at a tertiary eye hospital between October and December 2019. A RESCAN 700 was used for the intraoperative and CIRRUS HD-OCT was used for postoperative observation of vaulting. Subjective and objective refractions, anterior ocular segment, corneal morphology, intraocular pressure (IOP), anterior chamber volume (ACV), crystalline lens rise (CLR), white-to-white distance (WTW), anterior chamber depth (ACD), axial length, corneal endothelial cell density (ECD), and fundoscopy were examined. A multivariable analysis was performed to determine the factors independently associated with 1-month postoperative vaulting. RESULTS: Fifty-one patients (102 eyes) were included. Compared with the eyes with normal vaulting, those with high vaulting had higher preoperative diopter values (P = 0.039), lower preoperative corrected visual acuity (P = 0.006), lower preoperative IOP (P = 0.029), higher preoperative ACD (P = 0.004), lower preoperative CLR (P = 0.046), higher ICL spherical equivalent (P = 0.030), higher intraoperative vaulting (P < 0.001), and lower IOP at 1 month (P = 0.045). The multivariable analysis showed that the only factor independently associated with high vaulting at 1 month after surgery was the intraoperative vaulting value (odds ratio = 1.005, 95% confidence interval: 1.002-1.007, P < 0.001). The intraoperative and 1-month postoperative vaulting values were positively correlated (R2 = 0.562). CONCLUSIONS: The RESCAN700 system can be used to perform intraoperative optical coherence tomography to predict the vaulting value of ICL at 1 month.


Assuntos
Miopia , Lentes Intraoculares Fácicas , Humanos , Implante de Lente Intraocular , Miopia/cirurgia , Refração Ocular , Estudos Retrospectivos
16.
Int J Clin Pract ; 2022: 1828223, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277468

RESUMO

Background: Hematopoietic stem cell transplantation (HSCT) has become the main treatment for acute myeloid leukemia (AML) and has been studied in many systematic reviews (SRs), but strong conclusions have not been drawn yet. Objective: This study aimed to summarize and critically evaluate the methodological and evidence quality of SRs and meta-analysis on this topic. Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched for SRs/meta-analyses regarding HSCT for AML. Two reviewers assessed the quality of SRs/meta-analyses in line with AMSTAR-2 and evaluated the strength of evidence quality with the grading of the evaluation system (GRADE) for concerned outcomes independently. Results: 12 SR/Meta articles were included, and the AMSTAR-2 scale showed that the quality grade of all articles was low or very low. GRADE results showed 29 outcomes, 2 of which were high, 12 were moderate, and 15 were low. Limitations and inconsistency were the most important factors leading to degradation, followed by imprecision and publication bias. Allo-SCT had better OS and DFS benefits than auto-SCT and significantly reduced the relapse in intermediate-risk AML/CR1 patients. Auto-SCT was associated with lower TRM than allo-SCT but generally had higher relapse. The results should be confirmed further for the low or moderate evidence quality. Conclusion: Current SRs show that allo-SCT in the treatment of AML might improve the OS, RFS, and DFS. Auto-SCT has significantly lower TRM but higher RR. Whether bone marrow transplantation is superior to nonmyeloablative chemotherapy remains to be evaluated. Meanwhile, the quality of methodology needs to be further improved. The intensity of evidence was uneven, and the high-quality evidence of outcomes was lacking. Considering the limitations of our overview, more rigorous and scientific studies are needed to fully explore the efficacy of different interventions of HSCT in AML, and clinicians should be more cautious in the treatment.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Indução de Remissão , Revisões Sistemáticas como Assunto , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Recidiva
17.
J Appl Toxicol ; 42(10): 1662-1670, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35470462

RESUMO

Chlorpyrifos and cyfluthrin are insecticides commonly used in agriculture. The mixed residues of chlorpyrifos and cyfluthrin in the aquatic environment may have combined effects on nontarget species. Therefore, studying the combined toxic effects and mechanisms of pesticide mixtures is of great significance to environmental risk assessment. To evaluate the risk of combined exposure, we examined the effects of both compounds, separately and together, on motor activity, acetylcholinesterase (AChE) activity, and neurotransmitter levels in larval zebrafish. Chlorpyrifos exposure significantly reduced functional motor capacity (swim distance and velocity) and enhanced meandering, while cyfluthrin exposure alone had no significant effects on swim parameters. However, combined exposure significantly reduced total swimming distance and mean velocity and increased meandering. Both compounds alone and the combination significantly reduced AChE activity, and the combined effect was antagonistic. Combined exposure also significantly altered the concentrations of serotonin, serotonin precursors, and dopamine precursors, as well as concentrations of the amino acid neurotransmitters glycine, alanine, and aspartic acid. Combined exposure to chlorpyrifos and cyfluthrin exhibited distinct joint action modes in terms of neurobehavior, AChE activity, and neurotransmitter levels, thereby providing an experimental basis for assessing the combined exposure to chlorpyrifos and cyfluthrin's environmental risk.


Assuntos
Clorpirifos , Inseticidas , Acetilcolinesterase/metabolismo , Animais , Clorpirifos/metabolismo , Clorpirifos/toxicidade , Inseticidas/toxicidade , Larva/metabolismo , Neurotransmissores , Nitrilas , Piretrinas , Serotonina/metabolismo , Peixe-Zebra/metabolismo
18.
Plant Biotechnol J ; 19(8): 1523-1536, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33567151

RESUMO

Improving plant biomass yield and/or feedstock quality for highly efficient lignocellulose conversion has been the main research focus in genetic modification of switchgrass (Panicum virgatum L.), a dedicated model plant for biofuel production. Here, we proved that overexpression of miR396 (OE-miR396) leads to reduced plant height and lignin content mainly by reducing G-lignin monomer content. We identified nineteen PvGRFs in switchgrass and proved thirteen of them were cleaved by miR396. MiR396-targeted PvGRF1, PvGRF9 and PvGRF3 showed significantly higher expression in stem. By separately overexpressing rPvGRF1, 3 and 9, in which synonymous mutations abolished the miR396 target sites, and suppression of PvGRF1/3/9 activity via PvGRF1/3/9-SRDX overexpression in switchgrass, we confirmed PvGRF1 and PvGRF9 played positive roles in improving plant height and G-lignin content. Overexpression of PvGRF9 was sufficient to complement the defective phenotype of OE-miR396 plants. MiR396-PvGRF9 modulates these traits partly by interfering GA and auxin biosynthesis and signalling transduction and cell wall lignin, glucose and xylan biosynthesis pathways. Moreover, by enzymatic hydrolysis analyses, we found that overexpression of rPvGRF9 significantly enhanced per plant sugar yield. Our results suggest that PvGRF9 can be utilized as a candidate molecular tool in modifying plant biomass yield and feedstock quality.


Assuntos
MicroRNAs , Panicum , Biomassa , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Panicum/genética , Panicum/metabolismo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética
19.
Physiol Plant ; 172(2): 733-747, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33215699

RESUMO

As a conserved microRNA (miRNA) family in plants, miR408 is known to be involved in different abiotic stress responses, including drought. Interestingly, some studies indicated a species- and/or cultivar-specific drought-responsive characteristic of miR408 in plant drought stress. Moreover, the functions of miR408 in perennial grass species are unknown. In this study, we investigated the role of miR408 in perennial ryegrass (Lolium perenne L.) by withholding water for 10 days for both wild type and transgenic plants with heterologous expression of rice (Oryza sativa L.) miR408 gene, Os-miR408. The results showed that transgenic perennial ryegrass plants displayed morphological changes under normal growth conditions, such as curl leaves and sunken stomata, which could be related to decreased leaf water loss. Moreover, transgenic perennial ryegrass exhibited improved drought tolerance, as demonstrated by maintaining higher leaf relative water content (RWC), lower electrolyte leakage (EL), and less lipid peroxidation compared to WT plants under drought stress. Furthermore, the transgenic plants showed higher antioxidative capacity under drought. These results showed that the improved drought tolerance in Os-miR408 transgenic plants could be due to leaf morphological changes favoring the maintenance of water status and to increased antioxidative capacity protecting against the reactive oxygen species damages under stress. These findings implied that miR408 could serve as a potential target for genetic manipulations to engineer perennial grass plants for improved water stress tolerance.


Assuntos
Secas , Lolium , MicroRNAs/genética , Estresse Fisiológico , Regulação da Expressão Gênica de Plantas , Lolium/genética , Lolium/metabolismo , Oryza/genética , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo
20.
Proc Natl Acad Sci U S A ; 115(16): 4039-4044, 2018 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-29666317

RESUMO

The long-term stressful utilization of forests and grasslands has led to ecosystem degradation and C loss. Since the late 1970s China has launched six key national ecological restoration projects to protect its environment and restore degraded ecosystems. Here, we conducted a large-scale field investigation and a literature survey of biomass and soil C in China's forest, shrubland, and grassland ecosystems across the regions where the six projects were implemented (∼16% of the country's land area). We investigated the changes in the C stocks of these ecosystems to evaluate the contributions of the projects to the country's C sink between 2001 and 2010. Over this decade, we estimated that the total annual C sink in the project region was 132 Tg C per y (1 Tg = 1012 g), over half of which (74 Tg C per y, 56%) was attributed to the implementation of the projects. Our results demonstrate that these restoration projects have substantially contributed to CO2 mitigation in China.


Assuntos
Sequestro de Carbono , Carbono/análise , Conservação dos Recursos Naturais , Ecossistema , Biomassa , China , Conservação dos Recursos Naturais/legislação & jurisprudência , Conservação dos Recursos Naturais/estatística & dados numéricos , Florestas , Pradaria , Humanos , Plantas/química , Avaliação de Programas e Projetos de Saúde , Solo/química , Movimentos da Água
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