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1.
Cell ; 186(18): 3882-3902.e24, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37597510

RESUMO

Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and progenitor cells (HSPC) has remained unclear. We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programs of HSPC persisted for months to 1 year following severe COVID-19 and were associated with distinct transcription factor (TF) activities, altered regulation of inflammatory programs, and durable increases in myelopoiesis. HSPC epigenomic alterations were conveyed, through differentiation, to progeny innate immune cells. Early activity of IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirus infection model. Epigenetic reprogramming of HSPC may underlie altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.


Assuntos
COVID-19 , Memória Epigenética , Síndrome de COVID-19 Pós-Aguda , Animais , Humanos , Camundongos , Diferenciação Celular , COVID-19/imunologia , Modelos Animais de Doenças , Células-Tronco Hematopoéticas , Inflamação/genética , Imunidade Treinada , Monócitos/imunologia , Síndrome de COVID-19 Pós-Aguda/genética , Síndrome de COVID-19 Pós-Aguda/imunologia , Síndrome de COVID-19 Pós-Aguda/patologia
2.
Nature ; 621(7979): 602-609, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37704733

RESUMO

Vertebral bone is subject to a distinct set of disease processes from long bones, including a much higher rate of solid tumour metastases1-4. The basis for this distinct biology of vertebral bone has so far remained unknown. Here we identify a vertebral skeletal stem cell (vSSC) that co-expresses ZIC1 and PAX1 together with additional cell surface markers. vSSCs display formal evidence of stemness, including self-renewal, label retention and sitting at the apex of their differentiation hierarchy. vSSCs are physiologic mediators of vertebral bone formation, as genetic blockade of the ability of vSSCs to generate osteoblasts results in defects in the vertebral neural arch and body. Human counterparts of vSSCs can be identified in vertebral endplate specimens and display a conserved differentiation hierarchy and stemness features. Multiple lines of evidence indicate that vSSCs contribute to the high rates of vertebral metastatic tropism observed in breast cancer, owing in part to increased secretion of the novel metastatic trophic factor MFGE8. Together, our results indicate that vSSCs are distinct from other skeletal stem cells and mediate the unique physiology and pathology of vertebrae, including contributing to the high rate of vertebral metastasis.


Assuntos
Neoplasias da Mama , Linhagem da Célula , Metástase Neoplásica , Coluna Vertebral , Células-Tronco , Humanos , Neoplasias da Mama/patologia , Diferenciação Celular , Autorrenovação Celular , Metástase Neoplásica/patologia , Osteoblastos/citologia , Osteoblastos/patologia , Coluna Vertebral/citologia , Coluna Vertebral/patologia , Células-Tronco/citologia , Células-Tronco/metabolismo , Células-Tronco/patologia , Biomarcadores
3.
Proc Natl Acad Sci U S A ; 120(39): e2306288120, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37729198

RESUMO

Nonsmall cell lung cancer (NSCLC) is highly malignant with limited treatment options, platinum-based chemotherapy is a standard treatment for NSCLC with resistance commonly seen. NSCLC cells exploit enhanced antioxidant defense system to counteract excessive reactive oxygen species (ROS), which contributes largely to tumor progression and resistance to chemotherapy, yet the mechanisms are not fully understood. Recent studies have suggested the involvement of histones in tumor progression and cellular antioxidant response; however, whether a major histone variant H1.2 (H1C) plays roles in the development of NSCLC remains unclear. Herein, we demonstrated that H1.2 was increasingly expressed in NSCLC tumors, and its expression was correlated with worse survival. When crossing the H1c knockout allele with a mouse NSCLC model (KrasLSL-G12D/+), H1.2 deletion suppressed NSCLC progression and enhanced oxidative stress and significantly decreased the levels of key antioxidant glutathione (GSH) and GCLC, the catalytic subunit of rate-limiting enzyme for GSH synthesis. Moreover, high H1.2 was correlated with the IC50 of multiple chemotherapeutic drugs and with worse prognosis in NSCLC patients receiving chemotherapy; H1.2-deficient NSCLC cells presented reduced survival and increased ROS levels upon cisplatin treatment, while ROS scavenger eliminated the survival inhibition. Mechanistically, H1.2 interacted with NRF2, a master regulator of antioxidative response; H1.2 enhanced the nuclear level and stability of NRF2 and, thus, promoted NRF2 binding to GCLC promoter and the consequent transcription; while NRF2 also transcriptionally up-regulated H1.2. Collectively, these results uncovered a tumor-driving role of H1.2 in NSCLC and indicate an "H1.2-NRF2" antioxidant feedforward cycle that promotes tumor progression and chemoresistance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Humanos , Histonas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Antioxidantes , Fator 2 Relacionado a NF-E2/genética , Espécies Reativas de Oxigênio , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Glutationa , Modelos Animais de Doenças
4.
EMBO Rep ; 24(6): e56128, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-37042626

RESUMO

Surgery-induced renal ischemia and reperfusion (I/R) injury and nephrotoxic drugs like cisplatin can cause acute kidney injury (AKI), for which there is no effective therapy. Lipid accumulation is evident following AKI in renal tubules although the mechanisms and pathological effects are unclear. Here, we report that Ehmt2-encoded histone methyltransferase G9a is upregulated in patients and mouse kidneys after AKI. Renal tubular specific knockout of G9a (Ehmt2Ksp ) or pharmacological inhibition of G9a alleviates lipid accumulation associated with AKI. Mechanistically, G9a suppresses transcription of the lipolytic enzyme Ces1; moreover, G9a and farnesoid X receptor (FXR) competitively bind to the same promoter regions of Ces1. Ces1 is consistently observed to be downregulated in the kidney of AKI patients. Pharmacological inhibition of Ces1 increases lipid accumulation, exacerbates renal I/R-injury and eliminates the beneficial effects on AKI observed in Ehmt2Ksp mice. Furthermore, lipid-lowering atorvastatin and an FXR agonist alleviate AKI by activating Ces1 and reducing renal lipid accumulation. Together, our results reveal a G9a/FXR-Ces1 axis that affects the AKI outcome via regulating renal lipid accumulation.


Assuntos
Injúria Renal Aguda , Túbulos Renais , Camundongos , Animais , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Injúria Renal Aguda/genética , Injúria Renal Aguda/induzido quimicamente , Lipídeos , Rim/patologia , Camundongos Endogâmicos C57BL
5.
Nucleic Acids Res ; 51(D1): D315-D327, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36408909

RESUMO

tRNA molecules contain dense, abundant modifications that affect tRNA structure, stability, mRNA decoding and tsRNA formation. tRNA modifications and related enzymes are responsive to environmental cues and are associated with a range of physiological and pathological processes. However, there is a lack of resources that can be used to mine and analyse these dynamically changing tRNA modifications. In this study, we established tModBase (https://www.tmodbase.com/) for deciphering the landscape of tRNA modification profiles from epitranscriptome data. We analysed 103 datasets generated with second- and third-generation sequencing technologies and illustrated the misincorporation and termination signals of tRNA modification sites in ten species. We thus systematically demonstrate the modification profiles across different tissues/cell lines and summarize the characteristics of tRNA-associated human diseases. By integrating transcriptome data from 32 cancers, we developed novel tools for analysing the relationships between tRNA modifications and RNA modification enzymes, the expression of 1442 tRNA-derived small RNAs (tsRNAs), and 654 DNA variations. Our database will provide new insights into the features of tRNA modifications and the biological pathways in which they participate.


Assuntos
Bases de Dados Genéticas , Processamento Pós-Transcricional do RNA , RNA de Transferência , Humanos , Neoplasias/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA de Transferência/química , RNA de Transferência/metabolismo
6.
Cancer Sci ; 115(9): 2908-2922, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38979884

RESUMO

The relationship among polycystic ovary syndrome (PCOS), endometrial cancer (EC), and glycometabolism remains unclear. We explored shared genes between PCOS and EC, using bioinformatics to unveil their pathogenic connection and influence on EC prognosis. Gene Expression Omnibus datasets GSE226146 (PCOS) and GSE196033 (EC) were used. A protein-protein interaction (PPI) network was constructed to identify the central genes. Candidate markers were screened using dataset GSE54250. Differences in marker expression were confirmed in mouse PCOS and human EC tissues using RT-PCR and immunohistochemistry. The effect of PGD on EC proliferation and migration was explored using Ki-67 and Transwell assays. PGD's impact on the glycometabolic pathway within carbon metabolism was assessed by quantifying glucose content and lactic acid production. R software identified 31 common genes in GSE226146 and GSE196033. Gene Ontology functional classification revealed enrichment in the "purine nucleoside triphosphate metabolism process," with key Kyoto Encyclopedia of Genes and Genomes pathways related to "carbon metabolism." The PPI network identified 15 hub genes. HK2, NDUFS8, PHGDH, PGD, and SMAD3 were confirmed as candidate markers. The RT-PCR analysis validated distinct HK2 and PGD expression patterns in mouse PCOS ovarian tissue and human EC tissue, as well as in normal and EC cells. Transfection experiments with Ishikawa cells further confirmed PGD's influence on cell proliferation and migration. Suppression of PGD expression impeded glycometabolism within the carbon metabolism of EC cells, suggesting PGD as a significant PCOS risk factor impacting EC proliferation and migration through modulation of single carbon metabolism. These findings highlight PGD's pivotal role in EC onset and prognosis.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias do Endométrio , Síndrome do Ovário Policístico , Feminino , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Humanos , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Proliferação de Células/genética , Animais , Camundongos , Movimento Celular/genética , Mapas de Interação de Proteínas , Linhagem Celular Tumoral , Glucose/metabolismo , Regulação Neoplásica da Expressão Gênica , Biologia Computacional/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Hexoquinase
7.
Plant Biotechnol J ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39312475

RESUMO

It is well known that the overall quality of japonica/geng rice is superior to that of indica/xian rice varieties. However, the molecular mechanisms underlying the quality disparities between these two subspecies of rice are still largely unknown. In this study, we have pinpointed a gene homologous to SLR1, termed LCG1, exhibiting significant expression during early caryopsis development and playing a specific role in regulating rice chalkiness and taste by affecting the accumulation of grain storage components, starch granule structure and chain length distribution of amylopectin. LCG1 physically interacts with OsBP5 and indirectly influences the expression of the amylose synthesis gene Waxy (Wx) by hindering the transcriptional activity of the OsBP5/OsEBP89 complex. Notably, sequence variations in the promoter region of LCG1 result in enhanced transcription in japonica rice accessions. This leads to elevated LCG1 expression in CSSL-LCG1Nip, thereby enhancing rice quality. Our research elucidates the molecular mechanism underlying the impact of the LCG1-OsBP5/OsEBP89-Wx regulatory pathway on rice chalkiness and taste quality, offering new genetic resources for improving the indica rice quality.

8.
FASEB J ; 37(6): e22936, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37144417

RESUMO

The tumor suppressor p53 has been implicated in the pathogenesis of liver fibrosis. HERC5-mediated posttranslational ISG modification of the p53 protein is critical for controlling its activity. Here, we demonstrated that the expression of HERC5 and ISG15 is highly elevated, whereas p53 is downregulated, in fibrotic liver tissues of mice and transforming growth factor-ß1 (TGF-ß1)-induced LX2 cells. HERC5 siRNA clearly increased the protein expression of p53, but the mRNA expression of p53 was not obviously changed. The inhibition of lincRNA-ROR (ROR) downregulated HERC5 expression and elevated p53 expression in TGF-ß1-stimulated LX-2 cells. Furthermore, the expression of p53 was almost unchanged after TGF-ß1-stimulated LX-2 cells were co-transfected with a ROR-expressing plasmid and HERC5 siRNA. We further confirmed that miR-145 is a target gene of ROR. In addition, we also showed that ROR regulates the HERC5-mediated ISGylation of p53 through mir-145/ZEB2. Together, we propose that ROR/miR-145/ZEB2 might be involved in the course of liver fibrosis by regulating ISGylation of the p53 protein.


Assuntos
MicroRNAs , RNA Longo não Codificante , Humanos , Fator de Crescimento Transformador beta1/metabolismo , RNA Longo não Codificante/genética , Cirrose Hepática/metabolismo , Fibrose , RNA Interferente Pequeno , MicroRNAs/genética , Peptídeos e Proteínas de Sinalização Intracelular , Homeobox 2 de Ligação a E-box com Dedos de Zinco
9.
Biotechnol Bioeng ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39258327

RESUMO

Sucrose is a commonly utilized nutritive sweetener in food and beverages due to its abundance in nature and low production costs. However, excessive intake of sucrose increases the risk of metabolic disorders, including diabetes and obesity. Therefore, there is a growing demand for the development of nonnutritive sweeteners with almost no calories. d-Allulose is an ultra-low-calorie, rare six-carbon monosaccharide with high sweetness, making it an ideal alternative to sucrose. In this study, we developed a cell factory for d-allulose production from sucrose using Escherichia coli JM109 (DE3) as a chassis host. The genes cscA, cscB, cscK, alsE, and a6PP were co-expressed for the construction of the synthesis pathway. Then, the introduction of ptsG-F and knockout of ptsG, fruA, ptsI, and ptsH to reprogram sugar transport pathways resulted in an improvement in substrate utilization. Next, the carbon fluxes of the Embden-Meyerhof-Parnas and the pentose phosphate pathways were regulated by the inactivation of pfkA and zwf, achieving an increase in d-allulose titer and yield of 154.2% and 161.1%, respectively. Finally, scaled-up fermentation was performed in a 5 L fermenter. The titer of d-allulose reached 11.15 g/L, with a yield of 0.208 g/g on sucrose.

10.
Environ Sci Technol ; 58(9): 4438-4449, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38330552

RESUMO

Dechlorination of chloropyridines can eliminate their detrimental environmental effects. However, traditional dechlorination technology cannot efficiently break the C-Cl bond of chloropyridines, which is restricted by the uncontrollable nonselective species. Hence, we propose the carbonate species-activated hydrogen peroxide (carbonate species/H2O2) process wherein the selective oxidant (peroxymonocarbonate ion, HCO4-) and selective reductant (hydroperoxide anion, HO2-) controllably coexist by manipulation of reaction pH. Taking 2-chloropyridine (Cl-Py) as an example, HCO4- first induces Cl-Py into pyridine N-oxidation intermediates, which then suffer from the nucleophilic dechlorination by HO2-. The obtained dechlorination efficiencies in the carbonate species/H2O2 process (32.5-84.5%) based on the cooperation of HCO4- and HO2- are significantly higher than those in the HO2--mediated sodium hydroxide/hydrogen peroxide process (0-43.8%). Theoretical calculations confirm that pyridine N-oxidation of Cl-Py can effectively lower the energy barrier of the dechlorination process. Moreover, the carbonate species/H2O2 process exhibits superior anti-interference performance and low electric energy consumption. Furthermore, Cl-Py is completely detoxified via the carbonate species/H2O2 process. More importantly, the carbonate species/H2O2 process is applicable for efficient dehalogenation of halogenated pyridines and pyrazines. This work offers a simple and useful strategy to enhance the dehalogenation efficiency of halogenated organics and sheds new insights into the application of the carbonate species/H2O2 process in practical environmental remediation.


Assuntos
Peróxido de Hidrogênio , Piridinas , Peróxido de Hidrogênio/química , Oxirredução , Carbonatos
11.
J Fluoresc ; 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39352679

RESUMO

The rapid and accurate detection of programmed death-ligand 1 (PD-L1) expression is of great value in the diagnosis and treatment of tumors. ELISA-based traditional method is the gold standard for protein detection, but there are still some shortcomings, especially the antigen-antibody dependence, greatly increased the detection time and cost. This work constructed a label-free fluorescent probe for rapid and sensitive detection of PD-L1 using a truncated aptamer as recognition molecules and double-stranded DNA specific dyes (SYBR Green I) as signal units. After a series of optimization conditions, this probe has good detection capability for PD-L1 in buffer solution with the detection limit as low as 0.68 ng/mL. Due to the specific recognition ability of aptamer and target, this method also has good selectivity for PD-L1 detection. The recovery of PD-L1 in human serum samples ranges from 86.20 to 96.36%. Compared with other methods, this strategy does not need to be marked, and does not need other complex design and purification process, but simple operation process and strong anti-interference ability. The whole detection process can be completed within 20 min and has good application prospect. This work will provide reference for drug dosage and prognosis evaluation of specific tumor therapy.

12.
Appl Opt ; 63(10): 2683-2688, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38568552

RESUMO

Different from the scalar optical field with spatially uniform polarization, the vector optical field exhibits inhomogeneous distribution of polarization on the cross section. Manipulating the variation of polarization in a single optical beam is important to acquire a flexible and controllable focused optical field. Previous studies mainly focused on the vector optical field with its polarization varying along a circular trajectory of the Poincaré sphere. Here, we demonstrate the tight focusing behaviors of the vector optical field with the polarization varying along complex curves of the Poincaré sphere, which is generated by the joint modulation of azimuthal phase and amplitude distributions of orthogonally polarized components. The longitudinal polarization component with a multipolar pattern in rotational symmetry can be achieved with similar distribution of the total focused field. The transverse and longitudinal spin angular momentum distributions in the focal space are discussed. Approximately pure transverse spin angular momentum can be constructed and manipulated in the focal space, which provides the possibility to manipulate the 3D spin flux for the applications of nano and spin photonics.

13.
Nucleic Acids Res ; 50(D1): D421-D431, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34755848

RESUMO

tRNA-derived small RNA (tsRNA), a novel type of regulatory small noncoding RNA, plays an important role in physiological and pathological processes. However, the understanding of the functional mechanism of tsRNAs in cells and their role in the occurrence and development of diseases is limited. Here, we integrated multiomics data such as transcriptome, epitranscriptome, and targetome data, and developed novel computer tools to establish tsRFun, a comprehensive platform to facilitate tsRNA research (http://rna.sysu.edu.cn/tsRFun/ or http://biomed.nscc-gz.cn/DB/tsRFun/). tsRFun evaluated tsRNA expression profiles and the prognostic value of tsRNAs across 32 types of cancers, identified tsRNA target molecules utilizing high-throughput CLASH/CLEAR or CLIP sequencing data, and constructed the interaction networks among tsRNAs, microRNAs, and mRNAs. In addition to its data presentation capabilities, tsRFun offers multiple real-time online tools for tsRNA identification, target prediction, and functional enrichment analysis. In summary, tsRFun provides a valuable data resource and multiple analysis tools for tsRNA investigation.


Assuntos
Bases de Dados de Ácidos Nucleicos , MicroRNAs/genética , Neoplasias/genética , RNA Mensageiro/genética , Pequeno RNA não Traduzido/genética , RNA de Transferência/genética , Software , Sequenciamento de Cromatina por Imunoprecipitação , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Internet , MicroRNAs/classificação , MicroRNAs/metabolismo , Neoplasias/diagnóstico , Neoplasias/metabolismo , Neoplasias/mortalidade , Conformação de Ácido Nucleico , Prognóstico , RNA Mensageiro/classificação , RNA Mensageiro/metabolismo , Pequeno RNA não Traduzido/classificação , Pequeno RNA não Traduzido/metabolismo , RNA de Transferência/classificação , RNA de Transferência/metabolismo , Análise de Sobrevida , Transcriptoma
14.
J Anesth ; 38(2): 232-243, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38310577

RESUMO

PURPOSE: Lidocaine microspheres can prolong the analgesic time to 24-48 h, which still cannot meet the need of postoperative analgesia lasting more than 3 days. Therefore, we added Fe3O4 to the lidocaine microspheres and used an applied magnetic field to attract Fe3O4 to fix the microspheres around the target nerves, reducing the diffusion of magnetic lidocaine microspheres to the surrounding tissues and prolonging the analgesic time. METHODS: Fe3O4-lidocaine-PLGA microspheres were prepared by the complex-emulsion volatilization method to characterize and study the release properties in vitro. The neural anchoring properties and in vivo morphology of the drug were obtained by magnetic resonance imaging. The nerve blocking effect and analgesic effect of magnetic lidocaine microspheres were evaluated by animal experiments. RESULTS: The mean diameter of magnetically responsive lidocaine microspheres: 9.04 ± 3.23 µm. The encapsulation and drug loading of the microspheres were 46.18 ± 3.26% and 6.02 ± 1.87%, respectively. Magnetic resonance imaging showed good imaging of Fe3O4-Lidocain-PLGA microspheres, a drug-carrying model that slowed down the diffusion of the microspheres in the presence of an applied magnetic field. Animal experiments demonstrated that this preparation had a significantly prolonged nerve block, analgesic effect, and a nerve anchoring function. CONCLUSION: Magnetically responsive lidocaine microspheres can prolong analgesia by slowly releasing lidocaine, which can be immobilized around the nerve by a magnetic field on the body surface, avoiding premature diffusion of the microspheres to surrounding tissues and improving drug targeting.


Assuntos
Anestesia Local , Lidocaína , Animais , Lidocaína/farmacologia , Ácido Láctico , Microesferas , Analgésicos
15.
Cancer Sci ; 114(10): 3972-3983, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37607779

RESUMO

Carcinoma cells possess high proliferative and invasive potentials and exhibit a resilience against stresses, metabolic disorder, and therapeutic efforts. These properties are mainly acquired by genetic alterations including driver gene mutations. However, the detailed molecular mechanisms have not been fully elucidated. Here, we provide a novel mechanism connecting oncogenic signaling and the tumorigenic properties by a transforming growth factor-ß1-stimulated clone 22 (TSC-22) family protein, THG-1 (also called as TSC22D4). THG-1 is localized at the basal layer of normal squamous epithelium and overexpressed in squamous cell carcinomas (SCCs). THG-1 knockdown suppressed SCC cell proliferation, invasiveness, and xenograft tumor formation. In contrast, THG-1 overexpression promoted the EGF-induced proliferation and stratified epithelium formation. Furthermore, THG-1 is phosphorylated by the receptor tyrosine kinase (RTK)-RAS-ERK pathway, which promoted the oncogene-mediated tumorigenesis. Moreover, THG-1 involves in the alternative splicing of CD44 variants, a regulator of invasiveness, stemness, and oxidative stress resistance under the RTK pathway. These findings highlight the pivotal roles of THG-1 as a novel effector of SCC tumorigenesis, and the detection of THG-1 phosphorylation by our established specific antibody could contribute to cancer diagnosis and therapy.


Assuntos
Carcinoma de Células Escamosas , Humanos , Carcinogênese/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Sistema de Sinalização das MAP Quinases/genética , Oncogenes/genética , Fosforilação , Fatores de Transcrição/genética , Animais
16.
Brief Bioinform ; 22(4)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-33313674

RESUMO

Although long noncoding RNAs (lncRNAs) have significant tissue specificity, their expression and variability in single cells remain unclear. Here, we developed ColorCells (http://rna.sysu.edu.cn/colorcells/), a resource for comparative analysis of lncRNAs expression, classification and functions in single-cell RNA-Seq data. ColorCells was applied to 167 913 publicly available scRNA-Seq datasets from six species, and identified a batch of cell-specific lncRNAs. These lncRNAs show surprising levels of expression variability between different cell clusters, and has the comparable cell classification ability as known marker genes. Cell-specific lncRNAs have been identified and further validated by in vitro experiments. We found that lncRNAs are typically co-expressed with the mRNAs in the same cell cluster, which can be used to uncover lncRNAs' functions. Our study emphasizes the need to uncover lncRNAs in all cell types and shows the power of lncRNAs as novel marker genes at single cell resolution.


Assuntos
Bases de Dados de Ácidos Nucleicos , Regulação da Expressão Gênica , RNA Longo não Codificante , Análise de Célula Única , Software , Animais , Humanos , Anotação de Sequência Molecular , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética
17.
Opt Express ; 31(17): 28489-28502, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710902

RESUMO

Spiking neural networks (SNNs) offer powerful computation capability due to its event-driven nature and temporal processing. However, it is still limited to shallow structure and simple tasks due to the training difficulty. In this work, we propose a deep convolutional residual spiking neural network (DCRSNN) for text classification tasks. In the DCRSNN, the feature extraction is achieved via a convolution SNN with residual connection, using the surrogate gradient direct training technique. Classification is performed by a fully-connected network. We also suggest a hybrid photonic DCRSNN, in which photonic SNNs are used for classification with a converted training method. The accuracy of hard and soft reset methods, as well as three different surrogate functions, were evaluated and compared across four different datasets. Results indicated a maximum accuracy of 76.36% for MR, 91.03% for AG News, 88.06% for IMDB and 93.99% for Yelp review polarity. Soft reset methods used in the deep convolutional SNN yielded slightly better accuracy than their hard reset counterparts. We also considered the effects of different pooling methods and observation time windows and found that the convergence accuracy achieved by convolutional SNNs was comparable to that of convolutional neural networks under the same conditions. Moreover, the hybrid photonic DCRSNN also shows comparable testing accuracy. This work provides new insights into extending the SNN applications in the field of text classification and natural language processing, which is interesting for the resources-restrained scenarios.

18.
Trends Analyt Chem ; 1622023 May.
Artigo em Inglês | MEDLINE | ID: mdl-38106545

RESUMO

Biomarker detection has attracted increasing interest in recent years due to the minimally or non-invasive sampling process. Single entity analysis of biomarkers is expected to provide real-time and accurate biological information for early disease diagnosis and prognosis, which is critical to the effective disease treatment and is also important in personalized medicine. As an innovative single entity analysis method, nanopore sensing is a pioneering single-molecule detection technique that is widely used in analytical bioanalytical fields. In this review, we overview the recent progress of nanopore biomarker detection as new approaches to disease diagnosis. In highlighted studies, nanopore was focusing on detecting biomarkers of different categories of communicable and noncommunicable diseases, such as pandemic Covid-19, AIDS, cancers, neurologic diseases, etc. Various sensitive and selective nanopore detecting strategies for different types of biomarkers are summarized. In addition, the challenges, opportunities, and direction for future development of nanopore-based biomarker sensors are also discussed.

19.
EMBO Rep ; 22(6): e51649, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33855783

RESUMO

Pathological TDP-43 aggregation is characteristic of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP); however, how TDP-43 aggregation and function are regulated remain poorly understood. Here, we show that O-GlcNAc transferase OGT-mediated O-GlcNAcylation of TDP-43 suppresses ALS-associated proteinopathies and promotes TDP-43's splicing function. Biochemical and cell-based assays indicate that OGT's catalytic activity suppresses TDP-43 aggregation and hyperphosphorylation, whereas abolishment of TDP-43 O-GlcNAcylation impairs its RNA splicing activity. We further show that TDP-43 mutations in the O-GlcNAcylation sites improve locomotion defects of larvae and adult flies and extend adult life spans, following TDP-43 overexpression in Drosophila motor neurons. We finally demonstrate that O-GlcNAcylation of TDP-43 promotes proper splicing of many mRNAs, including STMN2, which is required for normal axonal outgrowth and regeneration. Our findings suggest that O-GlcNAcylation might be a target for the treatment of TDP-43-linked pathogenesis.


Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Esclerose Lateral Amiotrófica/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Splicing de RNA , RNA Mensageiro/genética
20.
Analyst ; 148(24): 6282-6291, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37971331

RESUMO

Raman imaging (RI) is an outstanding technique that enables molecular-level medical diagnostics and therapy assessment by providing characteristic fingerprint and morphological information about molecules. However, obtaining high-quality Raman images generally requires a long acquisition time, up to hours, which is prohibitive for RI applications of timely cytopathology and histopathology analyses. To address this issue, image super-resolution (SR) based on deep learning, including convolutional neural networks and transformers, has been widely recognized as an effective solution to reduce the time required for achieving high-quality RI. In this study, a locality enhanced transformer network (LETNet) is proposed to perform Raman image SR. Specifically, the general architecture of the transformer is adopted with the replacement of self-attention by convolution to generate high-fidelity and detailed SR images. Additionally, the convolution in the LETNet is further optimized by utilizing depth-wise convolution to improve the computational efficiency of the model. Experiments on hyperspectral Raman images of breast cancer cells and Raman images of a few channels of brain tumor tissues demonstrate that the LETNet achieves superior 2×, 4×, and 8× SR with fewer parameters compared with other SR methods. Consequently, high-quality Raman images can be obtained with a significant reduction in time, ranging from 4 to 64 times. Overall, the proposed method provides a novel, efficient, and reliable solution to expedite high-quality RI and promote its application in real-time diagnosis and therapy.


Assuntos
Aceleração , Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Citologia , Diagnóstico por Imagem , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador
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