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1.
Plant Cell ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39293039

RESUMO

The endosperm in cereal grains is instrumental in determining grain yield and seed quality, as it controls starch and seed storage protein (SSP) production. In this study, we identified a specific nuclear factor-Y (NF-Y) trimeric complex in wheat (Triticum aestivum L.), consisting of TaNF-YA3-D, TaNF-YB7-B, and TaNF-YC6-B, and exhibiting robust expression within the endosperm during grain filling. Knockdown of either TaNF-YA3 or TaNF-YC6 led to reduced starch but increased gluten protein levels. TaNF-Y indirectly boosted starch biosynthesis genes by repressing TaNAC019, a repressor of cytosolic small ADP-glucose pyrophosphorylase 1a (TacAGPS1a), sucrose synthase 2 (TaSuS2), and other genes involved in starch biosynthesis. Conversely, TaNF-Y directly inhibited the expression of Gliadin-γ-700 (TaGli-γ-700) and low molecular weight-400 (TaLMW-400). Furthermore, TaNF-Y components interacted with SWINGER (TaSWN), the histone methyltransferase subunit of Polycomb repressive complex 2 (PRC2), to repress TaNAC019, TaGli-γ-700, and TaLMW-400 expression through trimethylation of histone H3 at lysine 27 (H3K27me3) modification. Notably, weak mutation of FERTILIZATION INDEPENDENT ENDOSPERM (TaFIE), a core PRC2 subunit, reduced starch but elevated gliadin and LMW-GS contents. Intriguingly, sequence variation within the TaNF-YB7-B coding region was linked to differences in starch and SSP content. Distinct TaNF-YB7-B haplotypes affect its interaction with TaSWN-B, influencing the repression of targets like TaNAC019 and TaGli-γ-700. Our findings illuminate the intricate molecular mechanisms governing TaNF-Y-PRC2-mediated epigenetic regulation for wheat endosperm development. Manipulating the TaNF-Y complex holds potential for optimizing grain yield and enhancing grain quality.

2.
Sci China Life Sci ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38987431

RESUMO

Winter plants rely on vernalization, a crucial process for adapting to cold conditions and ensuring successful reproduction. However, understanding the role of histone modifications in guiding the vernalization process in winter wheat remains limited. In this study, we investigated the transcriptome and chromatin dynamics in the shoot apex throughout the life cycle of winter wheat in the field. Two core histone modifications, H3K27me3 and H3K36me3, exhibited opposite patterns on the key vernalization gene VERNALIZATION1 (VRN1), correlating with its induction during cold exposure. Moreover, the H3K36me3 level remained high at VRN1 after cold exposure, which may maintain its active state. Mutations in FERTILIZATION-INDEPENDENT ENDOSPERM (TaFIE) and SET DOMAIN GROUP 8/EARLY FLOWERING IN SHORT DAYS (TaSDG8/TaEFS), components of the writer complex for H3K27me3 and H3K36me3, respectively, affected flowering time. Intriguingly, VRN1 lost its high expression after the cold exposure memory in the absence of H3K36me3. During embryo development, VRN1 was silenced with the removal of active histone modifications in both winter and spring wheat, with selective restoration of H3K27me3 in winter wheat. The mutant of Tafie-cr-87, a component of H3K27me3 "writer" complex, did not influence the silence of VRN1 during embryo development, but rather attenuated the cold exposure requirement of winter wheat. Integrating gene expression with H3K27me3 and H3K36me3 patterns identified potential regulators of flowering. This study unveils distinct roles of H3K27me3 and H3K36me3 in controlling vernalization response, maintenance, and resetting in winter wheat.

3.
Adv Sci (Weinh) ; 11(33): e2401383, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38943260

RESUMO

Starch and seed storage protein (SSP) composition profoundly impact wheat grain yield and quality. To unveil regulatory mechanisms governing their biosynthesis, transcriptome, and epigenome profiling is conducted across key endosperm developmental stages, revealing that chromatin accessibility, H3K27ac, and H3K27me3 collectively regulate SSP and starch genes with varying impact. Population transcriptome and phenotype analyses highlight accessible promoter regions' crucial role as a genetic variation resource, influencing grain yield and quality in a core collection of wheat accessions. Integration of time-serial RNA-seq and ATAC-seq enables the construction of a hierarchical transcriptional regulatory network governing starch and SSP biosynthesis, identifying 42 high-confidence novel candidates. These candidates exhibit overlap with genetic regions associated with grain size and quality traits, and their functional significance is validated through expression-phenotype association analysis among wheat accessions and loss-of-function mutants. Functional analysis of wheat abscisic acid insensitive 3-A1 (TaABI3-A1) with genome editing knock-out lines demonstrates its role in promoting SSP accumulation while repressing starch biosynthesis through transcriptional regulation. Excellent TaABI3-A1Hap1 with enhanced grain weight is selected during the breeding process in China, linked to altered expression levels. This study unveils key regulators, advancing understanding of SSP and starch biosynthesis regulation and contributing to breeding enhancement.


Assuntos
Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Melhoramento Vegetal , Amido , Triticum , Triticum/genética , Triticum/metabolismo , Amido/genética , Amido/metabolismo , Amido/biossíntese , Redes Reguladoras de Genes/genética , Regulação da Expressão Gênica de Plantas/genética , Melhoramento Vegetal/métodos , Proteínas de Armazenamento de Sementes/genética , Proteínas de Armazenamento de Sementes/metabolismo , Fenótipo , Endosperma/genética , Endosperma/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
4.
J Integr Plant Biol ; 66(7): 1295-1312, 2024 Jul.
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.


Assuntos
Secas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Raízes de Plantas , Triticum , Água , Triticum/genética , Triticum/crescimento & desenvolvimento , Triticum/fisiologia , Triticum/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Água/metabolismo , Locos de Características Quantitativas/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Estresse Fisiológico/genética , Estudo de Associação Genômica Ampla , Resistência à Seca
5.
J Cell Mol Med ; 28(9): e18352, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685685

RESUMO

Gliomas, the most lethal tumours in brain, have a poor prognosis despite accepting standard treatment. Limited benefits from current therapies can be attributed to genetic, epigenetic and microenvironmental cues that affect cell programming and drive tumour heterogeneity. Through the analysis of Hi-C data, we identified a potassium-chloride co-transporter SLC12A5 associated with disrupted topologically associating domain which was downregulated in tumour tissues. Multiple independent glioma cohorts were included to analyse the characterization of SLC12A5 and found it was significantly associated with pathological features, prognostic value, genomic alterations, transcriptional landscape and drug response. We constructed two SLC12A5 overexpression cell lines to verify the function of SLC12A5 that suppressed tumour cell proliferation and migration in vitro. In addition, SLC12A5 was also positively associated with GABAA receptor activity and negatively associated with pro-tumour immune signatures and immunotherapy response. Collectively, our study provides a comprehensive characterization of SLC12A5 in glioma and supports SLC12A5 as a potential suppressor of disease progression.


Assuntos
Neoplasias Encefálicas , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma , Cotransportadores de K e Cl- , Simportadores , Humanos , Glioma/genética , Glioma/patologia , Glioma/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Simportadores/genética , Simportadores/metabolismo , Movimento Celular/genética , Prognóstico , Receptores de GABA-A/metabolismo , Receptores de GABA-A/genética
6.
Mol Plant ; 17(3): 438-459, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38310351

RESUMO

The spike architecture of wheat plays a crucial role in determining grain number, making it a key trait for optimization in wheat breeding programs. In this study, we used a multi-omic approach to analyze the transcriptome and epigenome profiles of the young spike at eight developmental stages, revealing coordinated changes in chromatin accessibility and H3K27me3 abundance during the flowering transition. We constructed a core transcriptional regulatory network (TRN) that drives wheat spike formation and experimentally validated a multi-layer regulatory module involving TaSPL15, TaAGLG1, and TaFUL2. By integrating the TRN with genome-wide association studies, we identified 227 transcription factors, including 42 with known functions and 185 with unknown functions. Further investigation of 61 novel transcription factors using multiple homozygous mutant lines revealed 36 transcription factors that regulate spike architecture or flowering time, such as TaMYC2-A1, TaMYB30-A1, and TaWRKY37-A1. Of particular interest, TaMYB30-A1, downstream of and repressed by WFZP, was found to regulate fertile spikelet number. Notably, the excellent haplotype of TaMYB30-A1, which contains a C allele at the WFZP binding site, was enriched during wheat breeding improvement in China, leading to improved agronomic traits. Finally, we constructed a free and open access Wheat Spike Multi-Omic Database (http://39.98.48.156:8800/#/). Our study identifies novel and high-confidence regulators and offers an effective strategy for dissecting the genetic basis of wheat spike development, with practical value for wheat breeding.


Assuntos
Estudo de Associação Genômica Ampla , Triticum , Triticum/genética , Melhoramento Vegetal , Redes Reguladoras de Genes/genética , Multiômica , Fatores de Transcrição/genética
8.
Nat Plants ; 9(6): 908-925, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37142750

RESUMO

Genetic transformation is important for gene functional study and crop improvement. However, it is less effective in wheat. Here we employed a multi-omic analysis strategy to uncover the transcriptional regulatory network (TRN) responsible for wheat regeneration. RNA-seq, ATAC-seq and CUT&Tag techniques were utilized to profile the transcriptional and chromatin dynamics during early regeneration from the scutellum of immature embryos in the wheat variety Fielder. Our results demonstrate that the sequential expression of genes mediating cell fate transition during regeneration is induced by auxin, in coordination with changes in chromatin accessibility, H3K27me3 and H3K4me3 status. The built-up TRN driving wheat regeneration was found to be dominated by 446 key transcription factors (TFs). Further comparisons between wheat and Arabidopsis revealed distinct patterns of DNA binding with one finger (DOF) TFs in the two species. Experimental validations highlighted TaDOF5.6 (TraesCS6A02G274000) and TaDOF3.4 (TraesCS2B02G592600) as potential enhancers of transformation efficiency in different wheat varieties.


Assuntos
Fatores de Transcrição , Triticum , Triticum/genética , Triticum/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Cromatina , Redes Reguladoras de Genes , Diferenciação Celular
9.
Chin Neurosurg J ; 9(1): 14, 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37170383

RESUMO

Intracranial pressure (ICP) is one of the most important indexes in neurosurgery. It is essential for doctors to determine the numeric value and changes of ICP, whether before or after an operation. Although external ventricular drainage (EVD) is the gold standard for monitoring ICP, more and more novel monitoring methods are being applied clinically.Invasive wired ICP monitoring is still the most commonly used in practice. Meanwhile, with the rise and development of various novel technologies, non-invasive types and invasive wireless types are gradually being used clinically or in the testing phase, as a complimentary approach of ICP management. By choosing appropriate monitoring methods, clinical neurosurgeons are able to obtain ICP values safely and effectively under particular conditions.This article introduces diverse monitoring methods and compares the advantages and disadvantages of different monitoring methods. Moreover, this review may enable clinical neurosurgeons to have a broader view of ICP monitoring.

10.
J Genet Genomics ; 50(11): 835-845, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36907353

RESUMO

Wheat is the most widely grown crop globally, providing 20% of the daily consumed calories and protein content around the world. With the growing global population and frequent occurrence of extreme weather caused by climate change, ensuring adequate wheat production is essential for food security. The architecture of the inflorescence plays a crucial role in determining the grain number and size, which is a key trait for improving yield. Recent advances in wheat genomics and gene cloning techniques have improved our understanding of wheat spike development and its applications in breeding practices. Here, we summarize the genetic regulation network governing wheat spike formation, the strategies used for identifying and studying the key factors affecting spike architecture, and the progress made in breeding applications. Additionally, we highlight future directions that will aid in the regulatory mechanistic study of wheat spike determination and targeted breeding for grain yield improvement.


Assuntos
Locos de Características Quantitativas , Triticum , Mapeamento Cromossômico , Melhoramento Vegetal , Grão Comestível/genética
11.
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
12.
Front Immunol ; 14: 1105489, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36845098

RESUMO

Glioma is the most common primary malignant tumor of the central nervous system in clinical practice. Most adult diffuse gliomas have poor efficacy after standard treatment, especially glioblastoma. With the in-depth understanding of brain immune microenvironment, immunotherapy as a new treatment has attracted much attention. In this study, through analyzing a large number of glioma cohorts, we reported that TSPAN7, a member of the tetraspanin family, decreased in high-grade gliomas and low expression was associated with poor prognosis in glioma patients. Meanwhile, the expression pattern of TSPAN7 was verified in glioma clinical samples and glioma cell lines by qPCR, Western Blotting and immunofluorescence. In addition, functional enrichment analysis showed that cell proliferation, EMT, angiogenesis, DNA repair and MAPK signaling pathways were activated in the TSPAN7 lower expression subgroup. Lentiviral plasmids were used to overexpress TSPAN7 in U87 and LN229 glioma cell lines to explore the anti-tumor role of TSPAN7 in glioma. Moreover, by analyzing the relationship between TSPAN7 expression and immune cell infiltration in multiple datasets, we found that TSPAN7 was significantly negatively correlated with the immune infiltration of tumor-related macrophages, especially M2-type macrophages. Further analysis of immune checkpoints showed that, the expression level of TSPAN7 was negatively correlated with the expression of PD-1, PD-L1 and CTLA-4. Using an independent anti-PD-1 immunotherapy cohorts of GBM, we demonstrated that TSPAN7 expression may had a synergistic effect with PD-L1 on the response to immunotherapy. Based on the above findings, we speculate that TSPAN7 can serve as a biomarker for prognosis and a potential immunotherapy target in glioma patients.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Adulto , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/metabolismo , Antígeno B7-H1/metabolismo , Glioma/genética , Glioma/terapia , Glioma/metabolismo , Imunoterapia , Microambiente Tumoral , Proteínas do Tecido Nervoso , Tetraspaninas/genética
13.
Genome Biol ; 24(1): 7, 2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639687

RESUMO

BACKGROUND: Plant and animal embryogenesis have conserved and distinct features. Cell fate transitions occur during embryogenesis in both plants and animals. The epigenomic processes regulating plant embryogenesis remain largely elusive. RESULTS: Here, we elucidate chromatin and transcriptomic dynamics during embryogenesis of the most cultivated crop, hexaploid wheat. Time-series analysis reveals stage-specific and proximal-distal distinct chromatin accessibility and dynamics concordant with transcriptome changes. Following fertilization, the remodeling kinetics of H3K4me3, H3K27ac, and H3K27me3 differ from that in mammals, highlighting considerable species-specific epigenomic dynamics during zygotic genome activation. Polycomb repressive complex 2 (PRC2)-mediated H3K27me3 deposition is important for embryo establishment. Later H3K27ac, H3K27me3, and chromatin accessibility undergo dramatic remodeling to establish a permissive chromatin environment facilitating the access of transcription factors to cis-elements for fate patterning. Embryonic maturation is characterized by increasing H3K27me3 and decreasing chromatin accessibility, which likely participates in restricting totipotency while preventing extensive organogenesis. Finally, epigenomic signatures are correlated with biased expression among homeolog triads and divergent expression after polyploidization, revealing an epigenomic contributor to subgenome diversification in an allohexaploid genome. CONCLUSIONS: Collectively, we present an invaluable resource for comparative and mechanistic analysis of the epigenomic regulation of crop embryogenesis.


Assuntos
Cromatina , Histonas , Animais , Histonas/metabolismo , Triticum/genética , Triticum/metabolismo , Desenvolvimento Embrionário/genética , Complexo Repressor Polycomb 2/metabolismo , Mamíferos/genética
14.
Sci China Life Sci ; 65(9): 1718-1775, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36018491

RESUMO

Bread wheat (Triticum aestivum L.) is a major crop that feeds 40% of the world's population. Over the past several decades, advances in genomics have led to tremendous achievements in understanding the origin and domestication of wheat, and the genetic basis of agronomically important traits, which promote the breeding of elite varieties. In this review, we focus on progress that has been made in genomic research and genetic improvement of traits such as grain yield, end-use traits, flowering regulation, nutrient use efficiency, and biotic and abiotic stress responses, and various breeding strategies that contributed mainly by Chinese scientists. Functional genomic research in wheat is entering a new era with the availability of multiple reference wheat genome assemblies and the development of cutting-edge technologies such as precise genome editing tools, high-throughput phenotyping platforms, sequencing-based cloning strategies, high-efficiency genetic transformation systems, and speed-breeding facilities. These insights will further extend our understanding of the molecular mechanisms and regulatory networks underlying agronomic traits and facilitate the breeding process, ultimately contributing to more sustainable agriculture in China and throughout the world.


Assuntos
Melhoramento Vegetal , Triticum , Genoma de Planta/genética , Genômica , Fenótipo , Locos de Características Quantitativas/genética , Triticum/genética
15.
Front Oncol ; 12: 844197, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35311111

RESUMO

Background: Germ cell tumors (GCTs) are neoplasms derived from reproductive cells, mostly occurring in children and adolescents at 10 to 19 years of age. Intracranial GCTs are classified histologically into germinomas and non-germinomatous germ cell tumors. Germinomas of the basal ganglia are difficult to distinguish based on symptoms or routine MRI images from gliomas, even for experienced neurosurgeons or radiologists. Meanwhile, intracranial germinoma has a lower incidence rate than glioma in children and adults. Therefore, we established a model based on pre-trained ResNet18 with transfer learning to better identify germinomas of the basal ganglia. Methods: This retrospective study enrolled 73 patients diagnosed with germinoma or glioma of the basal ganglia. Brain lesions were manually segmented based on both T1C and T2 FLAIR sequences. The T1C sequence was used to build the tumor classification model. A 2D convolutional architecture and transfer learning were implemented. ResNet18 from ImageNet was retrained on the MRI images of our cohort. Class activation mapping was applied for the model visualization. Results: The model was trained using five-fold cross-validation, achieving a mean AUC of 0.88. By analyzing the class activation map, we found that the model's attention was focused on the peri-tumoral edema region of gliomas and tumor bulk for germinomas, indicating that differences in these regions may help discriminate these tumors. Conclusions: This study showed that the T1C-based transfer learning model could accurately distinguish germinomas from gliomas of the basal ganglia preoperatively.

16.
Nat Commun ; 13(1): 1511, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35314680

RESUMO

Glioblastoma multiforme (GBM) remains the top challenge to radiotherapy with only 25% one-year survival after diagnosis. Here, we reveal that co-enhancement of mitochondrial fatty acid oxidation (FAO) enzymes (CPT1A, CPT2 and ACAD9) and immune checkpoint CD47 is dominant in recurrent GBM patients with poor prognosis. A glycolysis-to-FAO metabolic rewiring is associated with CD47 anti-phagocytosis in radioresistant GBM cells and regrown GBM after radiation in syngeneic mice. Inhibition of FAO by CPT1 inhibitor etomoxir or CRISPR-generated CPT1A-/-, CPT2-/-, ACAD9-/- cells demonstrate that FAO-derived acetyl-CoA upregulates CD47 transcription via NF-κB/RelA acetylation. Blocking FAO impairs tumor growth and reduces CD47 anti-phagocytosis. Etomoxir combined with anti-CD47 antibody synergizes radiation control of regrown tumors with boosted macrophage phagocytosis. These results demonstrate that enhanced fat acid metabolism promotes aggressive growth of GBM with CD47-mediated immune evasion. The FAO-CD47 axis may be targeted to improve GBM control by eliminating the radioresistant phagocytosis-proofing tumor cells in GBM radioimmunotherapy.


Assuntos
Antígeno CD47 , Glioblastoma , Animais , Antígeno CD47/metabolismo , Linhagem Celular Tumoral , Ácidos Graxos , Glioblastoma/genética , Glioblastoma/radioterapia , Humanos , Evasão da Resposta Imune , Camundongos , Fagocitose
17.
Front Oncol ; 12: 842973, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35186771

RESUMO

Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. Alteration in MAN2B1 has been proved to be accountable for several diseases. However, the relationship between MAN2B1 and glioma malignancy remains unclear. In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. We found that MAN2B1 was elevated in glioma and was correlated with malignant clinical and molecular features. Upregulated expression of MAN2B1 is prognostic for poor outcomes in glioma patients. Different frequencies of somatic mutations were found in gliomas between high and low MAN2B1 expression. Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. Functional enrichment analysis showed that MAN2B1 was involved in immune and inflammation processes. Moreover, MAN2B1 expression was strongly correlated with M2 macrophages and weakly correlated with M1 macrophages. Further analysis confirmed that MAN2B1 was closely associated with the markers of M2 macrophages and tumor-associated macrophages. Taken together, MAN2B1 is a potential prognostic biomarker in glioma and associates with immune infiltration.

18.
Chin Neurosurg J ; 6: 10, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922939

RESUMO

BACKGROUND: Invasive sphenoid sinus aspergillosis is a rare but life-threatening condition usually found in immunocompromised patients. When involving cavernous sinus and surrounding structures, patients are frequently misdiagnosed with a neoplasm or sellar abscess. Timely diagnosis and intervention are crucial to patients' outcomes. The objective of this study is to review cases of invasive sphenoid sinus aspergillosis to describe disease manifestations, imaging features, treatment, and outcome. CASE PRESENTATION: We describe four patients with invasive sphenoid sinus aspergillosis misdiagnosed as sellar tumors preoperatively. The mass was completely removed in three patients and partially removed in one patient microscopically. Pathological examinations confirmed Aspergillus in all cases. All four patients received anti-fungal agents postoperatively. There was no recurrence at the time of each patient's follow-up date. One patient with complete resection was lost to follow-up while the other three patients' neurologic function improved. Additionally, we performed a systematic review regarding invasive sphenoid sinus aspergillosis of existing English literature. CONCLUSION: With regard to clinical symptoms, headache, vision impairment, and ophthalmoplegia were observed in over half of the patients in the literature. A sellar mass with bone destruction on CT and involvement of cavernous sinus is highly suggestive of invasive fungal sphenoid sinusitis. Immediate surgical removal of the lesion is recommended for invasive sphenoid sinus aspergillosis to preserve nerve function and increase the likelihood of survival.

19.
New Phytol ; 228(1): 163-178, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32464682

RESUMO

Transport and homeostasis of transition metals in chloroplasts, which are accurately regulated to ensure supply and to prevent toxicity induced by these metals, are thus crucial for chloroplast function and photosynthetic performance. However, the mechanisms that maintain the balance of transition metals in chloroplasts remain largely unknown. We have characterized an albino-revertible green 1 (arg1) rice mutant. ARG1 encodes an evolutionarily conserved protein belonging to the ATP-binding cassette (ABC) transporter family. Protoplast transfection and immunogold-labelling assays showed that ARG1 is localized in the envelopes and thylakoid membranes of chloroplasts. Measurements of metal contents, metal transport, physiological and transcriptome changes revealed that ARG1 modulates cobalt (Co) and nickel (Ni) transport and homeostasis in chloroplasts to prevent excessive Co and Ni from competing with essential metal cofactors in chlorophyll and metal-binding proteins acting in photosynthesis. Natural allelic variation in ARG1 between indica and temperate japonica subspecies of rice is coupled with their different capabilities for Co transport and Co content within chloroplasts. This variation underpins the different photosynthetic capabilities in these subspecies. Our findings link the function of the ARG1 transporter to photosynthesis, and potentially facilitate breeding of rice cultivars with improved Co homeostasis and consequently improved photosynthetic performance.


Assuntos
Oryza , Transportadores de Cassetes de Ligação de ATP/metabolismo , Clorofila/metabolismo , Cloroplastos/metabolismo , Cobalto/metabolismo , Homeostase , Níquel/metabolismo , Níquel/toxicidade , Oryza/genética , Fotossíntese , Melhoramento Vegetal
20.
World Neurosurg ; 119: e262-e271, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30053568

RESUMO

OBJECTIVE: To assess the application of functional neuronavigation in surgeries of adult cerebral gliomas. METHODS: We performed a retrospective analysis of 375 cases of adult cerebral glioma patients who underwent microsurgical treatment between 2011 and 2017 in our department. Among them, 142 patients underwent surgery using functional neuronavigation (group A), and the other 233 patients were operated on without the help of functional neuronavigation (group B). For both groups, we categorized them into several subgroups according to the lesion locations. RESULTS: A significant difference in the gross total resection rate was observed between group A and group B (P = 0.001 for overall; P = 0.036 for EO area; and P = 0.004 for BBT area). The postoperative complication rate of group A was much lower than that of group B (P = 0.003 for overall; and P = 0.016 for BBT area). The postoperative 6-month Karnofsky Performance Scale score of all patients in group A was significantly higher than that of group B. Kaplan-Meier survival analyses showed significant increases in the median survival time of group A compared with that of group B (P < 0.001 for overall; P = 0.012 for EO area; P = 0.006 for BBT area), and the Cox proportional regression analysis estimated the hazard ratio of the functional neuronavigation to be 0.533, helping reduce the risk of death by 46.7%. CONCLUSIONS: This study confirmed that the application of neuronavigation in adult glioma surgery can improve postoperative quality of life and lengthen the survival time of patients, especially in cases involving the brainstem and the eloquent area.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Microcirurgia/métodos , Neuronavegação/métodos , Adolescente , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Glioma/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
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