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1.
EMBO J ; 42(8): e111472, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-36912149

RESUMO

For shade-intolerant plants, changes in light quality through competition from neighbors trigger shade avoidance syndrome (SAS): a series of morphological and physiological adaptations that are ultimately detrimental to plant health and crop yield. Phytochrome-interacting factor 7 (PIF7) is a major transcriptional regulator of SAS in Arabidopsis; however, how it regulates gene expression is not fully understood. Here, we show that PIF7 directly interacts with the histone chaperone anti-silencing factor 1 (ASF1). The ASF1-deprived asf1ab mutant showed defective shade-induced hypocotyl elongation. Histone regulator homolog A (HIRA), which mediates deposition of the H3.3 variant into chromatin, is also involved in SAS. RNA/ChIP-sequencing analyses identified the role of ASF1 in the direct regulation of a subset of PIF7 target genes. Furthermore, shade-elicited gene activation is accompanied by H3.3 enrichment, which is mediated by the PIF7-ASF1-HIRA regulatory module. Collectively, our data reveal that PIF7 recruits ASF1-HIRA to increase H3.3 incorporation into chromatin to promote gene transcription, thus enabling plants to effectively respond to environmental shade.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fitocromo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fator VII/genética , Fitocromo/genética , Cromatina/metabolismo , Epigênese Genética , Regulação da Expressão Gênica de Plantas , Proteínas de Ligação a DNA/metabolismo
2.
Environ Res ; 249: 118378, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38311206

RESUMO

With the advent of the second industrial revolution, mining and metallurgical processes generate large volumes of tailings and mine wastes (TMW), which worsens global environmental pollution. Studying the occurrence of metal and metalloid elements in TMW is an effective approach to evaluating pollution linked to TMW. However, traditional laboratory-based measurements are complicated and time-consuming; thus, an empirical method is urgently needed that can rapidly and accurately determine elemental occurrence forms. In this study, a model combining Bayesian optimization and random forest (RF) approaches was proposed to predict TMW occurrence forms. To build the RF model, a dataset of 2376 samples was obtained, with mineral composition, elemental properties, and total concentration composition used as inputs and the percentage of occurrence forms as the model output. The correlation coefficient (R), coefficient of determination, mean absolute error, root mean squared error, and root mean squared logarithmic error metrics were used for model evaluation. After Bayesian optimization, the optimal RF model achieved accurate predictive performance, with R values of 0.99 and 0.965 on the training and test sets, respectively. The feature significance was analyzed using feature importance and Shapley additive explanatory values, which revealed that the electronegativity and total concentration of the elements were the two features with the greatest influence on the model output. As the electronegativity of an element increases, its corresponding residual fraction content gradually decreases. This is because the solubility typically increases with the solvent's polarity and electronegativity. Overall, this study proposes an RF model based on the nature of TMW that can rapidly and accurately predict the percentage values of metal and metalloid element occurrence forms in TMW. This method can minimize testing time requirements and help to assess TMW pollution risks, as well as further promote safe TMW management and recycling.


Assuntos
Inteligência Artificial , Teorema de Bayes , Mineração , Resíduos Industriais/análise , Monitoramento Ambiental/métodos , Metais/análise
3.
J Chem Inf Model ; 63(20): 6316-6331, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37821422

RESUMO

Trichothecenes are highly toxic mycotoxins produced by Fusarium fungi, while TRI101/201 family enzymes play a crucial role in detoxification through acetylation. Studies on the substrate specificity and catalytic kinetics of TRI101/201 have revealed distinct kinetic characteristics, with significant differences observed in catalytic efficiency toward deoxynivalenol, while the catalytic efficiency for T-2 toxin remains relatively consistent. In this study, we used structural bioinformatics analysis and a molecular dynamics simulation workflow to investigate the mechanism underlying the differential catalytic activity of TRI101/201. The findings revealed that the binding stability between trichothecenes and TRI101/201 hinges primarily on a hydrophobic cage structure within the binding site. An intrinsic disordered loop, termed loop cover, defined the evolutionary patterns of the TRI101/201 protein family that are categorized into four subfamilies (V1/V2/V3/M). Furthermore, the unique loop displayed different conformations among these subfamilies' structures, which served to disrupt (V1/V2/V3) or reinforce (M) the hydrophobic cages. The disrupted cages enhanced the water exposure of the hydrophilic moieties of substrates like deoxynivalenol and thereby hindered their binding to the catalytic sites of V-type enzymes. In contrast, this water exposure does not affect substrates like T-2 toxin, which have more hydrophobic substituents, resulting in a comparable catalytic efficiency of both V- and M-type enzymes. Overall, our studies provide theoretical support for understanding the catalytic mechanism of TRI101/201, which shows how an intrinsic disordered loop could impact the protein-ligand binding and suggests a direction for rational protein design in the future.


Assuntos
Toxina T-2 , Tricotecenos , Tricotecenos/química , Tricotecenos/metabolismo , Tricotecenos/toxicidade , Sítios de Ligação , Água
4.
Proc Natl Acad Sci U S A ; 117(48): 30391-30399, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33199628

RESUMO

Nucleosome Assembly Protein 1 (NAP1) family proteins are evolutionarily conserved histone chaperones that play important roles in diverse biological processes. In this study, we determined the crystal structure of Arabidopsis NAP1-Related Protein 1 (NRP1) complexed with H2A-H2B and uncovered a previously unknown interaction mechanism in histone chaperoning. Both in vitro binding and in vivo plant rescue assays proved that interaction mediated by the N-terminal α-helix (αN) domain is essential for NRP1 function. In addition, the C-terminal acidic domain (CTAD) of NRP1 binds to H2A-H2B through a conserved mode similar to other histone chaperones. We further extended previous knowledge of the NAP1-conserved earmuff domain by mapping the amino acids of NRP1 involved in association with H2A-H2B. Finally, we showed that H2A-H2B interactions mediated by αN, earmuff, and CTAD domains are all required for the effective chaperone activity of NRP1. Collectively, our results reveal multiple interaction modes of a NAP1 family histone chaperone and shed light on how histone chaperones shield H2A-H2B from nonspecific interaction with DNA.


Assuntos
Histonas/química , Modelos Moleculares , Proteína 1 de Modelagem do Nucleossomo/química , Motivos de Aminoácidos , Aminoácidos , Arabidopsis , Sítios de Ligação , Sequência Conservada , Cristalografia por Raios X , Histonas/metabolismo , Proteína 1 de Modelagem do Nucleossomo/metabolismo , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas
5.
Nucleic Acids Res ; 48(1): 460-471, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31733060

RESUMO

As the largest group of MYB family transcription factors, R2R3-MYB proteins play essential roles during plant growth and development. However, the structural basis underlying how R2R3-MYBs recognize the target DNA remains elusive. Here, we report the crystal structure of Arabidopsis WEREWOLF (WER), an R2R3-MYB protein, in complex with its target DNA. Structural analysis showed that the third α-helices in both the R2 and R3 repeats of WER fit in the major groove of the DNA, specifically recognizing the DNA motif 5'-AACNGC-3'. In combination with mutagenesis, in vitro binding and in vivo luciferase assays, we showed that K55, N106, K109 and N110 are critical for the function of WER. Although L59 of WER is not involved in DNA binding in the structure, ITC analysis suggested that L59 plays an important role in sensing DNA methylation at the fifth position of cytosine (5mC). Like 5mC, methylation at the sixth position of adenine (6mA) in the AAC element also inhibits the interaction between WER and its target DNA. Our study not only unravels the molecular basis of how WER recognizes its target DNA, but also suggests that 5mC and 6mA modifications may block the interaction between R2R3-MYB transcription factors and their target genes.


Assuntos
Proteínas de Arabidopsis/química , Arabidopsis/genética , DNA de Plantas/química , Proteínas de Ligação a DNA/química , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/genética , Sequência de Aminoácidos , Animais , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sítios de Ligação , Galinhas/genética , Galinhas/metabolismo , Sequência Conservada , Cristalografia por Raios X , Metilação de DNA , DNA de Plantas/genética , DNA de Plantas/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Mamíferos , Modelos Moleculares , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
6.
Plant Biotechnol J ; 19(2): 212-214, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32741105

RESUMO

The rice black-streaked dwarf virus (RBSDV) disease causes severe rice yield losses in Asia. RNA interference (RNAi) has been widely applied to develop antiviral varieties in plants. So far, only a few studies reported the application of RNAi in rice against RBSDV and most of them are lack of enough data to support its breeding potential, which limited the progress on developing RBSDV-resistant variety. In this study, we generated three RNAi constructs to specifically target three RBSDV genes (S1, S2 and S6), respectively. We confirmed that RNAi targeting RBSDV S6 conferred rice with almost full immunity to RBSDV through phenotyping test in eight consecutive years in both artificial inoculation and field trials, while RNAi of S1 or S2 only leads to partially increased resistance. The S6RNAi was also found conferring strong resistance to southern rice black-streaked dwarf virus (SRBSDV), a novel species closely related to RBSDV that outbroke recently in Southern China. In particular, no adverse effects on agronomical and developmental traits were found in S6RNAi transgenic lines. The marker-free transgenic lines with S6RNAi, driven by either maize ubiquitin-1 promoter or rice rbcS green tissue expression promoter, in elite rice background should have great potential in breeding of resistant varieties to both RBSDV and SRBSDV and provide a basis for further safety evaluation and commercial application.


Assuntos
Oryza , Viroses , China , Oryza/genética , Melhoramento Vegetal , Doenças das Plantas/genética , Interferência de RNA
7.
Ecotoxicol Environ Saf ; 221: 112455, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34174735

RESUMO

The coexistence of various typical disinfectant pollutants has the potential to produce toxicity interaction towards organisms in the environment. A suitable model is necessary to evaluate the interaction quantitatively. Hence, the area-concentration ratio (ACR) method was modified (MACR) by combing confidence intervals to dynamically and quantitatively evaluate the toxicity interactions within disinfectant mixture pollutants. Disinfectant mixtures were designed by the direct equipartition design ray method using three guanidine disinfectants, chlorhexidine diacetate (CD), chlorhexidine (CHL), and polyhexamethylene biguanidine (POL) and one chlorine-containing disinfectant calcium hypochlorite (CAL). The toxicities of the four disinfectants and their mixtures towards Vibrio qinghaiensis sp.-Q67 (Q67) were determined by the time-dependent toxicity microplate analysis method. And the toxicity mechanism was analyzed by determining the effects of four disinfectants and their binary mixtures on the structure of cell, DNA and proteins (Pro) for Q67. The results show that the toxicities of CD and CHL to Q67vary little with time, but POL and CAL show the obvious time-dependent toxicity. The toxicities of CD, CHL and POL to Q67 are significantly stronger than that of CAL at the same exposure time. The toxicities of three binary mixture systems don't have significant difference in different exposure time. MACR can dynamically, quantitatively and accurately characterize toxicity interactions compared with ACR. According to MACR, the antagonism intensity dynamically changes with the prolongation of exposure time for binary mixture rays of three guanidine disinfectants and CAL, and linearly correlates with the components' concentration ratios. Four disinfectants all can destroy cell membrane and cause desaturation DNA of test organism, and CAL even can destroy the structure of DNA and protein. The probably reason for the antagonism within binary mixtures is the reaction between guanidine group and ClO-, which is called chemical antaogism.


Assuntos
Biguanidas/toxicidade , Compostos de Cálcio/toxicidade , Clorexidina/análogos & derivados , Clorexidina/toxicidade , Desinfetantes/toxicidade , Poluentes Ambientais/toxicidade , Vibrio/efeitos dos fármacos , Interações Medicamentosas
8.
Plant Cell ; 29(2): 260-276, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28138017

RESUMO

NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) defines an evolutionarily conserved family of histone chaperones and loss of function of the Arabidopsis thaliana NAP1 family genes NAP1-RELATED PROTEIN1 (NRP1) and NRP2 causes abnormal root hair formation. Yet, the underlying molecular mechanisms remain unclear. Here, we show that NRP1 interacts with the transcription factor WEREWOLF (WER) in vitro and in vivo and enriches at the GLABRA2 (GL2) promoter in a WER-dependent manner. Crystallographic analysis indicates that NRP1 forms a dimer via its N-terminal α-helix. Mutants of NRP1 that either disrupt the α-helix dimerization or remove the C-terminal acidic tail, impair its binding to histones and WER and concomitantly lead to failure to activate GL2 transcription and to rescue the nrp1-1 nrp2-1 mutant phenotype. Our results further demonstrate that WER-dependent enrichment of NRP1 at the GL2 promoter is involved in local histone eviction and nucleosome loss in vivo. Biochemical competition assays imply that the association between NRP1 and histones may counteract the inhibitory effect of histones on the WER-DNA interaction. Collectively, our study provides important insight into the molecular mechanisms by which histone chaperones are recruited to target chromatin via interaction with a gene-specific transcription factor to moderate chromatin structure for proper root hair development.


Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/crescimento & desenvolvimento , Proteínas de Ligação a DNA/fisiologia , Proteínas de Homeodomínio/fisiologia , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dimerização , Regulação da Expressão Gênica de Plantas , Histonas/metabolismo , Histonas/fisiologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Regiões Promotoras Genéticas
9.
Plant Physiol ; 176(2): 1341-1351, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29187567

RESUMO

Shade avoidance syndrome (SAS) allows a plant grown in a densely populated environment to maximize opportunities to access to sunlight. Although it is well established that SAS is accompanied by gene expression changes, the underlying molecular mechanism needs to be elucidated. Here, we identify the H3K4me3/H3K36me3-binding proteins, Morf Related Gene (MRG) group proteins MRG1 and MRG2, as positive regulators of shade-induced hypocotyl elongation in Arabidopsis (Arabidopsis thaliana). MRG2 binds PHYTOCHROME-INTERACTING FACTOR7 (PIF7) and regulates the expression of several common downstream target genes, including YUCCA8 and IAA19 involved in the auxin biosynthesis or response pathway and PRE1 involved in brassinosteroid regulation of cell elongation. In response to shade, PIF7 and MRG2 are enriched at the promoter and gene-body regions and are necessary for increase of histone H4 and H3 acetylation to promote target gene expression. Our study uncovers a mechanism in which the shade-responsive factor PIF7 recruits MRG1/MRG2 that binds H3K4me3/H3K36me3 and brings histone-acetylases to induce histone acetylations to promote expression of shade responsive genes, providing thus a molecular mechanistic link coupling the environmental light to epigenetic modification in regulation of hypocotyl elongation in plant SAS.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/metabolismo , Histonas/metabolismo , Acetilação , Proteínas de Arabidopsis/genética , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica de Plantas , Histonas/genética , Hipocótilo/genética , Hipocótilo/crescimento & desenvolvimento , Lisina/metabolismo , Metilação , Plantas Geneticamente Modificadas
10.
J Fuel Cell Sci Technol ; 12(1): 0110031-110037, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25642157

RESUMO

Thermal management in the fuel cell component of a direct fired solid oxide fuel cell gas turbine (SOFC/GT) hybrid power system can be improved by effective management and control of the cathode airflow. The disturbances of the cathode airflow were accomplished by diverting air around the fuel cell system through the manipulation of a hot-air bypass valve in open loop experiments, using a hardware-based simulation facility designed and built by the U.S. Department of Energy, National Energy Technology Laboratory (NETL). The dynamic responses of the fuel cell component and hardware component of the hybrid system were studied in this paper.

11.
Chemosphere ; 363: 142697, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38925515

RESUMO

The identification of arsenic (As)-contaminated areas is an important prerequisite for soil management and reclamation. Although previous studies have attempted to identify soil As contamination via machine learning (ML) methods combined with soil spectroscopy, they have ignored the rarity of As-contaminated soil samples, leading to an imbalanced learning problem. A novel ML framework was thus designed herein to solve the imbalance issue in identifying soil As contamination from soil visible and near-infrared spectra. Spectral preprocessing, imbalanced dataset resampling, and model comparisons were combined in the ML framework, and the optimal combination was selected based on the recall. In addition, Bayesian optimization was used to tune the model hyperparameters. The optimized model achieved recall, area under the curve, and balanced accuracy values of 0.83, 0.88, and 0.79, respectively, on the testing set. The recall was further improved to 0.87 with the threshold adjustment, indicating the model's excellent performance and generalization capability in classifying As-contaminated soil samples. The optimal model was applied to a global soil spectral dataset to predict areas at a high risk of soil As contamination on a global scale. The ML framework established in this study represents a milestone in the classification of soil As contamination and can serve as a valuable reference for contamination management in soil science.


Assuntos
Arsênio , Teorema de Bayes , Aprendizado de Máquina , Poluentes do Solo , Solo , Poluentes do Solo/análise , Solo/química , Arsênio/análise , Monitoramento Ambiental/métodos
12.
Protein Pept Lett ; 31(2): 141-152, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38243926

RESUMO

BACKGROUND: Antimicrobial peptides (AMPs) are promising alternative agents for antibiotics to overcome antibiotic resistance problems. But, it is difficult to produce large-scale antimicrobial research due to the toxicity towards expression hosts or degradation by peptidases in the host. Therefore, heterologous recombinant expression of antimicrobial peptides has always been a challenging issue. OBJECTIVES: To overcome toxicity to the expression host and low expression level, a new photocleavable protein fusion expression method for antimicrobial peptides is provided.3 Methods: Through directed evolution and high throughput screening, a photocleavable protein mutant R6-2-6-4 with a higher photocleavage efficiency was obtained. The DNA coding sequence of antimicrobial peptide Histatin 1 was fused within the sequence of R6-2-6-4 gene. The fusion gene was successfully expressed in Escherichia coli expression system. RESULTS: Antimicrobial peptide Histatin 1 could be successfully expressed and purified by fusing within PhoCl mutant R6-2-6-4. The antimicrobial activity was rarely affected, and the MIC value was 33 ug/mL, which was basically equivalent to 32 ug/mL of the chemically synthesized Histatin 1. After amplification in a 5 L fermenter, the expression of PhoCl mutant (R6-2-6-4)-Histatin1 improved up to 87.6 mg/L in fermenter, and Histatin1 obtained by photocleavage also could up to 11 mg/L. The prepared Histatin1 powder remained stable when stored at 4oC for up to 4 months without any degradation. In addition, the expression and photocleavage of ß -Defensin105 and Lysostaphin verified the certain universality of the PhoCl mutant fusion expression system. CONCLUSION: Antimicrobial peptides Histatin 1, ß -Defensin 105 and Lysostaphin were successfully expressed and purified by photocleavable protein mutant. This may provide a novel strategy to express and purify antimicrobial peptides in the Escherichia coli expression system.


Assuntos
Escherichia coli , Histatinas , Proteínas Recombinantes de Fusão , Histatinas/genética , Histatinas/metabolismo , Histatinas/química , Histatinas/farmacologia , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/metabolismo , Testes de Sensibilidade Microbiana , Peptídeos Antimicrobianos/genética , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/biossíntese , Peptídeos Antimicrobianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/biossíntese , Peptídeos Catiônicos Antimicrobianos/química , Humanos
13.
Biochim Biophys Acta Mol Cell Res ; 1871(8): 119840, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39216602

RESUMO

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide with a poor clinical prognosis. Protein phosphatase 1 regulatory subunit 14B (PPP1R14B) is an unidentified protein phosphatase 1 regulatory subunit that is associated with the occurrence and development of various cancers. Recently, PPP1R14B was found to contribute to paclitaxel resistance and cell progression in triple-negative breast cancer; however, the role of PPP1R14B in HCC is unknown. Here, we found that PPP1R14B was highly expressed in HCC tissues, which suggested a poor prognosis. Knockdown of PPP1R14B significantly inhibited the survival and tumorigenic ability of HCC cells, while overexpression of PPP1R14B had the opposite effects. Mechanistically, Ribosomal Protein S6 Kinase type 1(RPS6KA1) was identified as the target gene of PPP1R14B. PPP1R14B maintained the stability and phosphorylation of RPS6KA1, and positively regulated activation of the AKT/NF-κB pathway. Importantly, PPP1R14B-deficient tumor suppression could be partially restored by wild-type but not phosphorylated mutant RPS6KA1. Taken together, these findings shed light on the function and mechanism of PPP1R14B in HCC progression, indicating PPP1R14B is a promising molecular target for the treatment of HCC.

14.
Onco Targets Ther ; 17: 171-180, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476309

RESUMO

Purpose: Colorectal cancer (CRC) is one of the cancers with high incidence and mortality rates worldwide. In China, there are approximately 400,000 new CRC cases each year, seriously endangering people's life and health. Transforming growth factor ß-stimulated clone 22 domain family, member 2 (TSC22D2) is widely expression in cancers, but the role of TSC22D2 in CRC are still unknown. Methods: Real­time quantitative PCR (qRT-PCR) and Western blot were applied to determine the TSC22D2 levels. CCK-8, colony formation and transwell assays were used to determine the proliferation and metastasis abilities of CRC cells in vitro. In vivo metastatic potential was assessed using a subcutaneously injected mouse model and. Western-blot and immunoprecipitation experiments were used to study the mechanism of TSC22D2­mediated metastasis. Results: We found TSC22D2 was deregulated in CRC tissues and cells and implied poor prognosis. Overexpression TSC22D2 significantly promoted CRC cells proliferation and tumorigenicity both in vitro and vivo, whereas knockdown TSC22D2 resulted in the opposite effects. Importantly using a co-immunoprecipitation (co-IP) assay combined with mass spectrometry analysis to identify TSC22D2-interacting acyl-coenzyme A thioesterases 8 (ACOT8), TSC22D2 maintained stability of ACOT8. Overexpression of TCC22D2 in CRC cells can promote the expression of ACOT8 and inhibit the proliferation and metastasis of CRC cells through EMT mechanism, highlighting the possibility of TSC22D2 as a potential target in CRC development. Conclusion: In summary, the present study revealed the inhibitory effect of TSC22D2 on the proliferation of colorectal cancer cells, suggesting that TSC22D2 may be an important tumor suppressor and a potential therapeutic target during colorectal carcinogenesis.

15.
Biomed Pharmacother ; 170: 115955, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38048735

RESUMO

Immune-checkpoint blockade (ICB) therapies have been widely used in clinical treatment of cancer patients, but only 20-30% of patients benefit from immunotherapy. Therefore, it is important to decipher the molecular mechanism of resistance to ICB and develop new combined treatment strategies. PD-L1 up-regulation in tumor cells contributes to the occurrence of immune escape. Increasing evidence shows that its transcription level is affected by multiple factors, which limits the objective response rate of ICB. Fibroblast growth factor 19 (FGF19), a member of the fibroblast growth factor family, is widely involved in the malignant progression of many tumors by binding to fibroblast growth factor receptor 4 (FGFR4). In this study, we confirmed that FGF19 acts as a driver gene in hepatocellular carcinoma (HCC) progression by binding to FGFR4. The up-regulation of FGF19 and FGFR4 in HCC is associated with poor prognosis. We found that FGF19/FGFR4 promoted the proliferation and invasion of HCC cells by driving IGF2BP1 to promote PD-L1 expression. Knockdown of FGFR4 significantly reduced the expression of IGF2BP1/PD-L1 and inhibited the proliferation and invasion of HCC cells. These biological effects are achieved by inhibiting the PI3K/AKT pathway. The combination of FGFR4 knockdown and anti-PD-1 antibody greatly suppressed tumor growth and enhanced the sensitivity of immunotherapy, highlighting the clinical significance of FGF19/FGFR4 activation in immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Antígeno B7-H1/genética , Fosfatidilinositol 3-Quinases , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Linhagem Celular Tumoral
16.
Biochem Pharmacol ; 229: 116473, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39127151

RESUMO

Ubiquitin-specific peptidase 24 (USP24), a member of the deubiquitinase family, plays an important role in tumor regulation. However, the role of USP24 in Hepatocellular carcinoma(HCC)is unknown. The aim of our study was to explore the role of USP24 in HCC to seek new therapeutic targets for HCC. In this study, we found that USP24 was aberrantly upregulated in HCC tissues and predicted poor prognosis. USP24 markedly promoted HCC proliferation and progression in vitro and in vivo. Mechanistically, USP24 binds to tumor necrosis factor receptor-associated factor 2(TRAF2) and inhibits its degradation, thereby promoting the accumulation of TRAF2. Upregulation of TRAF2 activated protein kinase B/nuclear factor kappa-B (AKT/ NF-κB) signaling pathway and promoted HCC cell survival. In addition, USP24 positively correlated with programmed cell death ligand 1(PD-L1) expression in HCC, highlighting the clinical significance of USP24 activation in tumor immune evasion. Deletion of USP24 enhanced the tumor-killing ability of CD8+ T cells. Deletion of USP24 combined with anti-PD-1 antibody significantly enhanced the efficacy of HCC immunotherapy. Taken together, USP24 can be employed as a promising target to restrain tumor growth and increase the efficacy of HCC immunotherapy.

17.
Cell Rep ; 43(2): 113726, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38308844

RESUMO

Warm ambient conditions induce thermomorphogenesis and affect plant growth and development. However, the chromatin regulatory mechanisms involved in thermomorphogenesis remain largely obscure. In this study, we show that the histone methylation readers MORF-related gene 1 and 2 (MRG1/2) are required to promote hypocotyl elongation in response to warm ambient conditions. A transcriptome sequencing analysis indicates that MRG1/2 and phytochrome interacting factor 4 (PIF4) coactivate a number of thermoresponsive genes, including YUCCA8, which encodes a rate-limiting enzyme in the auxin biosynthesis pathway. Additionally, MRG2 physically interacts with PIF4 to bind to thermoresponsive genes and enhances the H4K5 acetylation of the chromatin of target genes in a PIF4-dependent manner. Furthermore, MRG2 competes with phyB for binding to PIF4 and stabilizes PIF4 in planta. Our study indicates that MRG1/2 activate thermoresponsive genes by inducing histone acetylation and stabilizing PIF4 in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fitocromo , Histonas , Vernalização , Arabidopsis/genética , Cromatina , Metilação , Proteínas de Arabidopsis/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas Cromossômicas não Histona
18.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 30(6): 1321-5, 2013 Dec.
Artigo em Zh | MEDLINE | ID: mdl-24645619

RESUMO

Electroencephalogram (EEG) signals provide an objective physiological index for the identification of the driver's fatigue state. It is very important to choose appropriate channels and EEG signal features adaptively due to the features varying with different subjects and time. A support vector machine (SVM) based increasing feature selection algorithm for driving fatigue EEG classification is presented in this paper. The algorithm is a method to select EEG channels and features for driving fatigue adaptively in an ascending order. We can select the optimal feature each time from the remaining candidate features using the optimized SVM model minimum error rate as the index. The experimental calculation has characteristics of using 16 electrode channels which cover the whole head in the main area, of selecting 208 candidate features as the initial set, of selecting to the EEG data calculation recorded in 5 different time periods of a subject, and of choosing error rate of 2% as the algorithm termination condition. The selected features and models, therefore, can reach a high level of classification and generalization ability.


Assuntos
Algoritmos , Eletroencefalografia , Fadiga , Máquina de Vetores de Suporte , Condução de Veículo , Eletrodos , Humanos , Fatores de Tempo
19.
Environ Sci Process Impacts ; 25(9): 1564-1577, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37646127

RESUMO

Cosmetic additives (ADDs) and packaging plasticizers (PLAs) probably present potential risks and dangers to the environment and human body as emerging pollutants. To investigate their potential risks and dangers, five ADDs including methyl paraben (MET), ethyl paraben (ETH), propyl paraben (PRO), butyl-hydroxy anisole (BHA), and salicylic acid (SAL), as well as three PLAs including bisphenol A (BPA), bisphenol S (BPS) and tris(2-butoxyethyl) phosphate (TBEP) were selected as research objects, and ten mixture rays (R1-R10) composed of the eight components were designed by the uniform design ray (UD-Ray) method. The toxicities of the eight cosmetic pollutants and their eight-component mixture system towards Vibrio qinghaiensis sp.-Q67 (Q67) were systematically determined by the time-dependent microplate toxicity analysis (t-MTA) method. The three-dimensional (3D) surface of deviation from the concentration addition model (dCA) was utilized to qualitatively and quantitatively analyse the toxicity interaction of the mixtures and the correlation between toxicity interaction and the components' concentration ratios. Finally, eight individual pollutants and representative rays with significant inhibitory and interactive effects were selected to analyse DNA and soluble proteolysis as well as the microstructure and morphology of Q67 after treatment with single chemicals and their mixtures. The results showed that the eight cosmetic pollutants had conspicuous concentration-dependent toxicity and acute toxicity, and none of them, except BPS, BPA and ETH, had time-dependent toxicity. All rays had time/concentration-dependent toxicity and acute toxicity. At the same time, the toxicity interaction of these mixture rays was predominantly antagonism and the strongest antagonism appeared at high concentrations at 12 h. Nevertheless, the components' concentration ratio (pi) was the decisive factor for the type of mixture interaction. The correlation analysis revealed a significant positive linear correlation between mixture toxicity and pETH and pBPA, which indicated that ETH and BPA were the key components of the toxic effects. However, there was a significant negative linear correlation between the antagonism intensity and pBPA and pTBEP, which demonstrated that BPA and TBEP were the key components of the antagonism intensity. Pollutants and their mixtures can also damage cellular structures, and mixtures can exacerbate the dissolution of DNA and soluble proteins.


Assuntos
Cosméticos , Poluentes Ambientais , Vibrio , Humanos , Parabenos
20.
Anal Chem ; 84(19): 8378-82, 2012 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-22957474

RESUMO

Free chlorine was found to be able to destroy the passivated surface of the graphene quantum dots (GQDs) obtained by pyrolyzing citric acid, resulting in significant quenching of their fluorescence (FL) signal. After optimizing some experimental conditions (including response time, concentration of GQDs, and pH value of solution), a green and facile sensing system has been developed for the detection of free residual chlorine in water based on FL quenching of GQDs. The sensing system exhibits many advantages, such as short response time, excellent selectivity, wide linear response range, and high sensitivity. The linear response range of free chlorine (R(2) = 0.992) was from 0.05 to 10 µM. The detection limit (S/N = 3) was as low as 0.05 µM, which is much lower than that of the most widely used N-N-diethyl-p-phenylenediamine (DPD) colorimetric method. This sensing system was finally used to detect free residual chlorine in local tap water samples. The result agreed well with that by the DPD colorimetric method, suggesting the potential application of this new, green, sensitive, and facile sensing system in drinking water quality monitoring.


Assuntos
Cloro/análise , Água Potável/química , Grafite/química , Pontos Quânticos , Fluorescência , Microscopia de Força Atômica , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta
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