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SINA (Seven in absentia) E3 ubiquitin ligases are a family of RING (really interesting new gene) E3 ubiquitin ligases, and they play a crucial role in regulating plant growth and development, hormone response, and abiotic and biotic stress. However, there is little research on the SINA gene family in U. rhynchophylla. In this study, a total of 10 UrSINA genes were identified from the U. rhynchophylla genome. The results of multiple sequence alignments and chromosomal locations show that 10 UrSINA genes were unevenly located on 22 chromosomes, and each UrSINA protein contained a SINA domain at the N-terminal and RING domains at the C-terminal. Synteny analysis showed that there are no tandem duplication gene pairs and there are four segmental gene pairs in U. rhynchophylla, contributing to the expansion of the gene family. Furthermore, almost all UrSINA genes contained the same gene structure, with three exons and two introns, and there were many cis-acting elements relating to plant hormones, light responses, and biotic and abiotic stress. The results of qRT-PCR show that most UrSINA genes were expressed in stems, with the least expression in roots; meanwhile, most UrSINA genes and key enzyme genes were responsive to ABA and MeJA hormones with overlapping but different expression patterns. Co-expression analysis showed that UrSINA1 might participate in the TIA pathway under ABA treatment, and UrSINA5 and UrSINA6 might participate in the TIA pathway under MeJA treatment. The mining of UrSINA genes in the U. rhynchophylla provided novel information for understanding the SINA gene and its function in plant secondary metabolites, growth, and development.
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Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Reguladores de Crescimento de Plantas , Ubiquitina-Proteína Ligases , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta , Estresse Fisiológico/genética , Perfilação da Expressão Gênica , Sintenia , Cromossomos de Plantas/genéticaRESUMO
microRNAs (miRNAs) are small, non-coding RNAs that regulate expression of multiple genes. MiR-193a-3p functions as a tumor suppressor in many cancer types, but its effect on inducing specific anti-tumor immune responses is unclear. Therefore, we examined the effect of our lipid nanoparticle (LNP) formulated, chemically modified, synthetic miR-193a-3p mimic (INT-1B3) on anti-tumor immunity. INT-1B3 inhibited distant tumor metastasis and significantly prolonged survival. INT-1B3-treated animals were fully protected against challenge with autologous tumor cells even in absence of treatment indicating long-term immunization. Protection against autologous tumor cell challenge was hampered upon T cell depletion and adoptive T cell transfer abrogated tumor growth. Transfection of tumor cells with our miR-193a-3p mimic (1B3) resulted in tumor cell death and apoptosis accompanied by increased expression of DAMPs. Co-culture of 1B3-transfected tumor cells and immature DC led to DC maturation and these mature DC were able to stimulate production of type 1 cytokines by CD4+ and CD8+ T cells. CD4-CD8- T cells also produced type 1 cytokines, even in response to 1B3-transfected tumor cells directly. Live cell imaging demonstrated PBMC-mediated cytotoxicity against 1B3-transfected tumor cells. These data demonstrate for the first time that miR-193a-3p induces long-term immunity against tumor development via modulation of the tumor microenvironment and induction of immunogenic cell death.
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MicroRNAs , Nanopartículas , Microambiente Tumoral , MicroRNAs/genética , Animais , Microambiente Tumoral/imunologia , Camundongos , Humanos , Nanopartículas/química , Morte Celular Imunogênica/efeitos dos fármacos , Linhagem Celular Tumoral , Linfócitos T/imunologia , Linfócitos T/metabolismo , Apoptose , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Camundongos Endogâmicos C57BL , Imunidade Celular , Linfócitos T CD8-Positivos/imunologia , Feminino , Transfecção , Neoplasias/imunologia , Neoplasias/genética , Neoplasias/patologia , Citocinas/metabolismo , LipossomosRESUMO
Maturing immunometabolic research empowers immune regulation novel approaches. Progressive metabolic adaptation of tumor cells permits a thriving tumor microenvironment (TME) in which immune cells always lose the initial killing capacity, which remains an unsolved dilemma even with the development of immune checkpoint therapies. In recent years, many studies on tumor immunometabolism have been reported. The development of immunometabolism may facilitate anti-tumor immunotherapy from the recurrent crosstalk between metabolism and immunity. Here, we discuss clinical studies of the core signaling pathways of immunometabolism and their inhibitors or agonists, as well as the specific functions of these pathways in regulating immunity and metabolism, and discuss some of the identified immunometabolic checkpoints. Understanding the comprehensive advances in immunometabolism helps to revise the status quo of cancer treatment. An overview of the new landscape of immunometabolism. The PI3K pathway promotes anabolism and inhibits catabolism. The LKB1 pathway inhibits anabolism and promotes catabolism. Overactivation of PI3K/AKT/mTOR pathway and IDO, IL4I1, ACAT, Sirt2, and MTHFD2 promote immunosuppression of TME formation, as evidenced by increased Treg and decreased T-cell proliferation. The LKBI-AMPK pathway promotes the differentiation of naive T cells to effector T cells and memory T cells and promotes anti-tumor immunity in DCs.
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Non-SMC condensin II complex subunit D3 (NCAPD3) is a subunit of the non-structural maintenance of chromosomes condensin II complex, which involves chromosome condensation and segregation during mitosis. NCAPD3 has recently been demonstrated as a crucial oncogenic factor. However, the underlying mechanism of NCAPD3 in prostate cancer (PCa) remains not completely clear. In this study, we confirmed that lncRNA MALAT1 was induced by NCAPD3-STAT3, and the expression of miR-30a-5p was controlled by NCAPD3 in PCa cells by miRNA-seq. Through quantitative real-time PCR, fluorescence in situ hybridization, western blotting, and immunohistochemistry assay, we demonstrated that miR-30a-5p was lowly expressed in PCa cells and tissues compared to the controls, which was contrary to NCAPD3 expression and markedly downregulated by NCAPD3. Then, MALAT1 was analyzed for the complementary sequence in the potential interaction with miR-30a-5p by using the predicted target module of public databases. Dual-luciferase reporter assay and RNA immunoprecipitation were carried out to verify that MALAT1 functioned as a sponge for miR-30a-5p to reduce miR-30a-5p expression. Meanwhile, MYC acted as a transcriptional repressor to directly bind the promoter of the miR-30a-5p located gene and repress the miR-30a-5p expression. Furthermore, the upregulation of NCAPD3 on cell viability and migration was significantly attenuated in PC-3 cells when miR-30a-5p was overexpressed. NCAPD3 overexpression also accelerated tumor growth in the xenograft mouse model and repressed miR-30-5p. In summary, this work elucidates NCAPD3 inhibits miR-30a-5p through two pathways: increasing STAT3-MALAT1 to sponge miR-30a-5p and increasing MYC to directly inhibit miR-30a-5p transcription, which could serve as potential therapeutic targets for prostate cancer.
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CULLIN (CUL) protein is a subtype of E3 ubiquitin ligase that is involved in a variety of biological processes and responses to stress in plants. In Uncaria rhynchophylla, the CUL gene family has not been identified and its role in plant development, stress response and secondary metabolite synthesis has not been studied. In this study, 12 UrCUL gene members all contained the typical N-terminal domain and C-terminal domain identified from the U. rhynchophylla genome and were classified into four subfamilies based on the phylogenetic relationship with CULs in Arabidopsis thaliana. They were unevenly distributed on eight chromosomes but had a similar structural composition in the same subfamily, indicating that they were relatively conserved and potentially had similar gene functions. An interspecific and intraspecific collinearity analysis showed that fragment duplication played an important role in the evolution of the CUL gene family. The analysis of the cis-acting elements suggests that the UrCULs may play an important role in various biological processes, including the abscisic acid (ABA) response. To investigate this hypothesis, we treated the roots of U. rhynchophylla tissue-cultured seedlings with ABA. The expression pattern analysis showed that all the UrCUL genes were widely expressed in roots with various expression patterns. The co-expression association analysis of the UrCULs and key enzyme genes in the terpenoid indole alkaloid (TIA) synthesis pathway revealed the complex expression patterns of 12 UrCUL genes and some key TIA enzyme genes, especially UrCUL1, UrCUL1-likeA, UrCUL2-likeA and UrCUL2-likeB, which might be involved in the biosynthesis of TIAs. The results showed that the UrCULs were involved in the response to ABA hormones, providing important information for elucidating the function of UrCULs in U. rhynchophylla. The mining of UrCULs in the whole genome of U. rhynchophylla provided new information for understanding the CUL gene and its function in plant secondary metabolites, growth and development.
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Uncaria rhynchophylla is an evergreen vine plant, belonging to the Rubiaceae family, that is rich in terpenoid indole alkaloids (TIAs) that have therapeutic effects on hypertension and Alzheimer's disease. GATA transcription factors (TF) are a class of transcription regulators that participate in the light response regulation, chlorophyll synthesis, and metabolism, with the capability to bind to GATA cis-acting elements in the promoter region of target genes. Currently the charactertics of GATA TFs in U. rhynchophylla and how different light qualities affect the expression of GATA and key enzyme genes, thereby affecting the changes in U. rhynchophylla alkaloids have not been investigated. In this study, 25 UrGATA genes belonging to four subgroups were identified based on genome-wide analysis. Intraspecific collinearity analysis revealed that only segmental duplications were identified among the UrGATA gene family. Collinearity analysis of GATA genes between U. rhynchophylla and four representative plant species, Arabidopsis thaliana, Oryza sativa, Coffea Canephora, and Catharanthus roseus was also performed. U. rhynchophylla seedlings grown in either red lights or under reduced light intensity had altered TIAs content after 21 days. Gene expression analysis reveal a complex pattern of expression from the 25 UrGATA genes as well as a number of key TIA enzyme genes. UrGATA7 and UrGATA8 were found to have similar expression profiles to key enzyme TIA genes in response to altered light treatments, implying that they may be involved in the regulation TIA content. In this research, we comprehensively analyzed the UrGATA TFs, and offered insight into the involvement of UrGATA TFs from U. rhynchophylla in TIAs biosynthesis.
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Arabidopsis , Alcaloides de Triptamina e Secologanina , Uncaria , Luz , Luz Vermelha , Fatores de Transcrição GATARESUMO
Resident consumption is an important link to smooth the domestic circulation and promote the economy to achieve high-quality development. To stimulate the vitality of residents' consumption and achieve the expansion and quality of consumption, we should not only focus on the scale and willingness of residents to consume, but also consider the motivation of consumption. The paper analyzes the impact of intergenerational income mobility on residents' marginal propensity to consume and consumption altruism motive by expanding the Over Lapping Generation Models and combining the China Family Panel Studies (CFPS) data. The results of the study show: Intergenerational Income Elasticity has a significant positive effect on residents' marginal propensity to consume. When Intergenerational Income Elasticity increases, the "altruistic motive" of residents' consumption will also increase significantly. Compared with rural residents, Intergenerational Income Elasticity has a stronger positive effect on urban residents' marginal propensity to consume and marginal propensity to consume education. With the effect of intergenerational factors, urban residents' consumption shows stronger altruistic motives.
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Altruísmo , Desenvolvimento Econômico , Renda , Humanos , Povo Asiático , China , MotivaçãoRESUMO
Antibiotics and heavy metals added to livestock and poultry feed are excreted in manure, which is added to agricultural soil and causes severe pollution. However, the effects of oxytetracycline (OTC) and zinc (Zn), which are present at relatively high levels in feed additives, on antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and microbial communities have not been comprehensively studied. This study evaluated the effects of OTC and Zn on environmental factors, microorganisms, MGEs, and ARGs. The expression of MGEs in soil was stimulated by adding Zn at concentrations of 500 and 1000 mg/kg or OTC at concentrations of 30 and 100 mg/kg; however, the addition of their combination hindered the expression of MGEs in soil. The abundance of total MGEs and ARGs tended to decrease with increasing concentrations of Zn and OTC and the number of incubation days. Low and high OTC concentrations strongly inhibited sul and tet resistance genes, respectively. Network analysis showed that changes in the population of Firmicutes and Proteobacteria had the greatest impact on ARG abundance. Redundancy analysis revealed that MGEs, particularly intI2, facilitated the transfer and spread of ARGs and had the greatest impact on changes in ARG abundance. These findings provide reference values for the prevention and resolution of ecological and environmental risks posed by the presence of Zn and OTC in organic manure soil.
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Microbiota , Oxitetraciclina , Antibacterianos/toxicidade , Antibacterianos/análise , Oxitetraciclina/toxicidade , Zinco/toxicidade , Zinco/análise , Solo , Esterco/microbiologia , Genes Bacterianos , Resistência Microbiana a Medicamentos/genética , Sequências Repetitivas Dispersas , Microbiologia do SoloRESUMO
BACKGROUND: The dietary nutritional status of pregnant women is critical for maintaining the health of both mothers and infants. Food exchange systems have been employed in the nutritional guidance of patients in China, although their application in the dietary guidance of healthy pregnant women is quite limited. This study aimed to develop a novel food exchange system for Chinese pregnant women (NFES-CPW) and evaluate the relative validation of its application. METHODS: NFES-CPW covers approximately 500 types of food from ten categories and has more elaborate food portion sizes. It established a recommendation index for guiding food selection and used energy, water content, and protein as the exchange basis to balance the supply of energy and important nutrients throughout pregnancy. Furthermore, dietitians used the NFES-CPW and traditional food exchange system to generate new recipes based on the sample recipe. There were 40 derived recipes for each of the two food exchange methods. The food consumption, energy, and key nutrients of each recipe were calculated, and the differences between the two food exchange systems were compared using the Wilcoxon rank sum test or the Chi-square test. RESULTS: The results revealed that compared to those derived from traditional food exchange system, the NFES-CPW derived recipes had a better dietary structure, as evidenced by the intakes of whole-grain cereals, beans excluding soybeans, potatoes, fruits, fish, shrimp and shellfish, as well as eggs (P < 0.05), which were more conducive to reaching the recommended range of balanced dietary pagoda. After calculating energy and nutrients, although these two food exchange systems have similar effects on the dietary energy and macronutrient intake of pregnant women, the intake of micronutrients in NFES-CPW derived recipes was significantly higher than that from the traditional food exchange system, which was more conducive to meeting the dietary requirements of pregnant women. The outstanding improvement are primarily vitamin A, vitamin B2, folic acid, vitamin B12, vitamin C, calcium, iron, and iodine (P < 0.05). Moreover, when compared to recipes obtained from the traditional food exchange system, the error ranges of energy and most nutrients were significantly reduced after employing the NFES-CPW. CONCLUSIONS: Therefore, NFES-CPW is an appropriate tool that adheres to Chinese dietary characteristics and can provide suitable dietary guidance to pregnant women.
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Ingestão de Energia , Estado Nutricional , Gestantes , Feminino , Humanos , Gravidez , Dieta , População do Leste Asiático , Vitaminas , Política NutricionalRESUMO
Uncaria rhynchophylla (Miq.) Miq. ex Havil, a traditional medicinal herb, is enriched with several pharmacologically active terpenoid indole alkaloids (TIAs). At present, no method has been reported that can comprehensively select and evaluate the appropriate reference genes for gene expression analysis, especially the transcription factors and key enzyme genes involved in the biosynthesis pathway of TIAs in U. rhynchophylla. Reverse transcription quantitative PCR (RT-qPCR) is currently the most common method for detecting gene expression levels due to its high sensitivity, specificity, reproducibility, and ease of use. However, this methodology is dependent on selecting an optimal reference gene to accurately normalize the RT-qPCR results. Ten candidate reference genes, which are homologues of genes used in other plant species and are common reference genes, were used to evaluate the expression stability under three stress-related experimental treatments (methyl jasmonate, ethylene, and low temperature) using multiple stability analysis methodologies. The results showed that, among the candidate reference genes, S-adenosylmethionine decarboxylase (SAM) exhibited a higher expression stability under the experimental conditions tested. Using SAM as a reference gene, the expression profiles of 14 genes for key TIA enzymes and a WRKY1 transcription factor were examined under three experimental stress treatments that affect the accumulation of TIAs in U. rhynchophylla. The expression pattern of WRKY1 was similar to that of tryptophan decarboxylase (TDC) under ETH treatment. This research is the first to report the stability of reference genes in U. rhynchophylla and provides an important foundation for future gene expression analyses in U. rhynchophylla. The RT-qPCR results indicate that the expression of WRKY1 is similar to that of TDC under ETH treatment. It may coordinate the expression of TDC, providing a possible method to enhance alkaloid production in the future through synthetic biology.
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Transcrição Reversa , Fatores de Transcrição , Fatores de Transcrição/genética , Reprodutibilidade dos Testes , Reação em Cadeia da PolimeraseRESUMO
Cyclometalated iridium complexes with mitochondrial targeting show great potential as substitutes for platinum-based complexes because of their strong anti-cancer properties. Three novel cyclometalated iridium(III) compounds were synthesized and evaluated in five different cell lines as part of the ongoing systematic investigations of these compounds. The complexes were prepared using 4,7-dichloro-1,10-phenanthroline ligands. The cytotoxicity of complexes Ir1-Ir3 towards HeLa cells was shown to be high, with IC50 values of 0.83±0.06, 4.73±0.11, and 4.95±0.62 µM, respectively. Complex Ir1 could be ingested by HeLa cells in 3 h and has shown high selectivity toward mitochondria. Subsequent investigations demonstrated that Ir1 triggered apoptosis in HeLa cells by augmenting the generation of reactive oxygen species (ROS), reducing the mitochondrial membrane potential, and depleting ATP levels. Furthermore, the movement of cells was significantly suppressed and the progression of the cell cycle was arrested in the G0/G1 phase following the administration of Ir1. The Western blot analysis demonstrated that the induction of apoptosis in HeLa cells by Ir1 involves the activation of the mitochondria-dependent channel and the PI3K/AKT signaling pathway. No significant cytotoxicity was observed in zebrafish embryos at concentrations less than or equal to 16 µM, e.g., survival rate and developmental abnormalities. In vivo, antitumor assay demonstrated that Ir1 suppressed tumor growth in mice. Therefore, our work shows that complex Ir1 could be a promising candidate for developing novel antitumor drugs.
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Antineoplásicos , Complexos de Coordenação , Humanos , Camundongos , Animais , Células HeLa , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo , Irídio/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Complexos de Coordenação/farmacologia , Complexos de Coordenação/metabolismo , Peixe-Zebra/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Apoptose , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Proliferação de CélulasRESUMO
Tumor-associated macrophage (TAM) affects the intrinsic properties of tumor cells and the tumor microenvironment (TME), which can stimulate tumor cell proliferation, migration, and genetic instability, and macrophage diversity includes the diversity of tumors with different functional characteristics. Macrophages are now a central drug target in various diseases, especially in the TME, which, as "tumor promoters" and "immunosuppressors", have different responsibilities during tumor development and accompany by significant dynamic alterations in various subpopulations. Remodelling immunosuppression of TME and promotion of pre-existing antitumor immune responses is critical by altering TAM polarization, which is relevant to the efficacy of immunotherapy, and uncovering the exact mechanism of action of TAMs and identifying their specific targets is vital to optimizing current immunotherapies. Hence, this review aims to reveal the triadic interactions of macrophages with programmed death and oncotherapy, and to integrate certain relationships in cancer treatment.
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A novel multi-color emitting Na2 YMg2 V3 O12 :Sm3+ phosphor was synthesized using a solid-state reaction, and its crystal structure, luminescence properties, and thermal stability were studied. Charge transfer within the (VO4 )3- groups in the Na2 YMg2 V3 O12 host led to a broad emission band between 400 and 700 nm, with a maximum at 530 nm. The Na2 Y1-x Mg2 V3 O12 :xSm3+ phosphors exhibited a multi-color emission band under 365 nm near-ultraviolet (near-UV) light, consisting of the green emission of the (VO4 )3- groups and sharp emission peaks at 570 nm (yellow), 618 nm (orange), 657 nm (red), and 714 nm (deep red) of Sm3+ ions. The optimal doping concentration of Sm3+ ions was found to be 0.05 mol%, and the dipole-dipole (d-d) interaction was primarily responsible for the concentration quenching phenomenon. Using the acquired Na2 YMg2 V3 O12 :Sm3+ phosphors, commercial BaMgAl10 O17 :Eu2+ blue phosphor, and a near-UV light-emitting diode (LED) chip, a white-LED lamp was designed and packaged. It produced bright neutral white light, manifesting a CIE coordinate of (0.314, 0.373), a color rendering index (CRI) of 84.9, and a correlated color temperature (CCT) of 6377 K. These findings indicate the potential of Na2 YMg2 V3 O12 :Sm3+ phosphor to be used as a multi-color component for solid-state illumination.
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Iluminação , Luminescência , Sódio , Raios Ultravioleta , TemperaturaRESUMO
Protoplast-based engineering has become an important tool for basic plant molecular biology research and developing genome-edited crops. Uncaria rhynchophylla is a traditional Chinese medicinal plant with a variety of pharmaceutically important indole alkaloids. In this study, an optimized protocol for U. rhynchophylla protoplast isolation, purification, and transient gene expression was developed. The best protoplast separation protocol was found to be 0.8 M D-mannitol, 1.25% Cellulase R-10, and 0.6% Macerozyme R-10 enzymolysis for 5 h at 26 °C in the dark with constant oscillation at 40 rpm/min. The protoplast yield was as high as 1.5 × 107 protoplasts/g fresh weight, and the survival rate of protoplasts was greater than 90%. Furthermore, polyethylene glycol (PEG)-mediated transient transformation of U. rhynchophylla protoplasts was investigated by optimizing different crucial factors affecting transfection efficiency, including plasmid DNA amount, PEG concentration, and transfection duration. The U. rhynchophylla protoplast transfection rate was highest (71%) when protoplasts were transfected overnight at 24 °C with the 40 µg of plasmid DNA for 40 min in a solution containing 40% PEG. This highly efficient protoplast-based transient expression system was used for subcellular localization of transcription factor UrWRKY37. Finally, a dual-luciferase assay was used to detect a transcription factor promoter interaction by co-expressing UrWRKY37 with a UrTDC-promoter reporter plasmid. Taken together, our optimized protocols provide a foundation for future molecular studies of gene function and expression in U. rhynchophylla.
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Perfilação da Expressão Gênica , Protoplastos , Protoplastos/metabolismo , Perfilação da Expressão Gênica/métodos , Fatores de Transcrição/metabolismo , DNA/metabolismoRESUMO
WRKY transcription factors, as the largest gene family in higher plants, play an important role in various biological processes including growth and development, regulation of secondary metabolites, and stress response. In this study, we performed genome-wide identification and analysis of WRKY transcription factors in S. siamensis. A total of 59 SsWRKY genes were identified that were distributed on all 14 chromosomes, and these were classified into three major groups based on phylogenetic relationships. Each of these groups had similar conserved motifs and gene structures. We compared all the S. siamensis SsWRKY genes with WRKY genes identified from three diverse plant species, and the results implied that segmental duplication and tandem duplication play an important roles in the evolution processes of the WRKY gene family. Promoter region analysis revealed that SsWRKY genes included many cis-acting elements related to plant growth and development, phytohormone response, and both abiotic and biotic stress. Expression profiles originating from the transcriptome database showed expression patterns of these SsWRKY genes in four different tissues and revealed that most genes are expressed in plant roots. Fifteen SsWRKY genes with low-temperature response motifs were surveyed for their gene expression under cold stress, showing that most genes displayed continuous up-regulation during cold treatment. Our study provides a foundation for further study on the function and regulatory mechanism of the SsWRKY gene family.
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Epigenetic proteins are one of the important targets in the current research fields of cancer therapy. A family of bromodomain-containing (BRD) and extra terminal domain (BET) proteins act as epigenetic readers to regulate the expression of key oncogenes and anti-apoptotic proteins. Recently, although BET degraders based on PROTAC technology have achieved significant antitumor effects, the lack of selectivity for BET protein degradation has not been fully addressed. Herein, a series of small molecule BRD4 PROTACs were designed and synthesized. Most of the degraders were effective in inhibiting MM.1S and MV-4-11 cell lines, especially in MV-4-11. Among them, degrader 8b could induce the degradation of BRD4 and exhibited a time- and concentration-dependent depletion manner and there was a significant depletion of BRD4, laying a foundation for effectively treating leukemia and multiple myeloma. Moreover, 8b could also effectively prevent the activation of MRC5 cells by inducing the degradation of BRD4 protein, which preliminarily proves that the BRD4 degrader based on the PROTAC concept has great potential for the treatment of pulmonary fibrosis. Taken together, these findings laid a foundation for BRD4 degraders as an effective strategy for treating related diseases.
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Leucemia , Mieloma Múltiplo , Humanos , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Linhagem Celular Tumoral , Mieloma Múltiplo/metabolismo , Proteínas de Ciclo Celular/metabolismoRESUMO
BACKGROUND: Liver cancer is one of the common malignancies. The dysregulation of metabolism is a driver of accelerated tumourigenesis. Metabolic changes are well documented to maintain tumour growth, proliferation and survival. Recently, a variety of polyphenols have been shown to have a crucial role both in liver disease prevention and metabolism regulation. METHODS: We conducted a literature search and combined recent data with systematic analysis to comprehensively describe the molecular mechanisms that link polyphenols to metabolic regulation and their contribution in liver protection and liver cancer prevention. RESULTS: Targeting metabolic dysregulation in organisms prevents and resists the development of liver cancer, which has important implications for identifying new therapeutic strategies for the management and treatment of cancer. Polyphenols are a class of complex compounds composed of multiple phenolic hydroxyl groups and are the main active ingredients of many natural plants. They mediate a broad spectrum of biological and pharmacological functions containing complex lipid metabolism, glucose metabolism, iron metabolism, intestinal flora imbalance, as well as the direct interaction of their metabolites with key cell-signalling proteins. A large number of studies have found that polyphenols affect the metabolism of organisms by interfering with a variety of intracellular signals, thereby protecting the liver and reducing the risk of liver cancer. CONCLUSION: This review systematically illustrates that various polyphenols, including resveratrol, chlorogenic acid, caffeic acid, dihydromyricetin, quercetin, catechins, curcumin, etc., improve metabolic disorders through direct or indirect pathways to protect the liver and fight liver cancer.
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Neoplasias Hepáticas , Polifenóis , Humanos , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Resveratrol/farmacologia , Antioxidantes/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controleRESUMO
The application of livestock manure is the leading cause of antibiotic and heavy metal pollution in agricultural soil. However, the effects of oxytetracycline (OTC) and lead (Pb) pollution in the single or combined form on antibiotic resistance genes (ARGs) in the soil need to be further studied. This study was planned to investigate the effects of OTC and Pb application on ARGs, mobile genetic elements (MGEs), and bacterial abundance in the soil. The relative abundance of ARGs and MGEs increased by 0.31-fold and 0.03-fold after the addition of 80 mg kg-1 Pb to the soil, and by 0.49-fold and 0.03-fold after the addition of 160 mg kg-1 Pb. In addition, under the premise of the existence of OTC, the inhibitory effect of a low concentration of Pb on ARG is stronger than that of a high concentration of Pb, resulting in a lower abundance of ARGs. The abundance of ARGs and MGEs increased by 0.11-fold and 0.17-fold after the addition of OTC (30 mg kg-1) to the soil at a Pb concentration of 80 mg kg-1 and by 0.18-fold and 0.04-fold at a Pb concentration of 160 mg kg-1. The addition of OTC and Pb in the soil also decreased the many bacterial communities such as Bacteroidetes, Proteobacteria, Acidobacteria, and Firmicutes. Redundancy analysis (RDA) showed that organic matter content and pH were positively correlated with the abundance of ARGs and MGEs. At the same time, electrical conductivity (EC) had a negative correlation with the abundance of ARGs and MGEs in the soil. Intl1 was significantly associated with tetB, sul1, tetQ, sul2, and sul3. Network analysis illustrated that Actinobacteria, Bacteroidetes, and Proteobacteria were the main host bacteria causing changes in the abundance of ARGs and MGEs, and they were also predominant phylum in the culture environment. This conclusion can provide a reference for the related research of ARGs in soil.
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Microbiota , Oxitetraciclina , Oxitetraciclina/farmacologia , Solo/química , Antibacterianos/farmacologia , Antibacterianos/análise , Genes Bacterianos , Chumbo/análise , Resistência Microbiana a Medicamentos/genética , Esterco/microbiologia , Bactérias/genética , Microbiologia do Solo , Sequências Repetitivas DispersasRESUMO
The practical application of nanoscale zero-valent iron (NZVI) is restricted by its easy oxidation and aggregation. Here, sludge biochar (SB) was used as a carrier to stabilize NZVI for Cd2+ and Cu2+ removal. SB supported NZVI (SB-NZVI) was synthesized using the carbothermic method. The superior preparation conditions, structural characteristics, and performance and mechanisms of the SB-NZVI composites for the removal of Cd2+ and Cu2+ were investigated via batch experiments and characterization analysis. The optimal removal capacities of 55.94 mg/g for Cd2+ and 97.68 mg/g for Cu2+ were achieved at a Fe/sludge mass ratio of 1:4 and pyrolysis temperature of 900 °C. Batch experiments showed that the SB-NZVI (1:4-900) composite had an excellent elimination capacity over a broad pH range, and that weakly acidic to neutral solutions were optimal for removal. The XPS results indicated that the Cd2+ removal was mainly dependent on the adsorption and precipitation/coprecipitation, while reduction and adsorption were the mechanisms that play a decisive role in Cu2+ removal. The presence of Cd2+ had an opposite effect on the Cu2+ removal. Moreover, the SB-NZVI composites made of municipal sludge greatly reduces the leaching toxicity and bio-availability of heavy metals in the municipal sludge, which can be identified as an environmentally-friendly material.
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Ferro , Poluentes Químicos da Água , Ferro/química , Cádmio , Esgotos , Poluentes Químicos da Água/análise , AdsorçãoRESUMO
Tert-butylperoxy-2-ethylhexanoate (TBPEH) and tert-butyl peroxybenzoate (TBPB) promote the radical acylation of allyl ester with benzaldehyde to synthesize new carbonyl-containing compounds under solvent-free and metal-free conditions. This reaction is compatible with electron-donating and halogen groups and has excellent atom utilization and chemical selectivity. Furthermore, the synthetic compounds can further apply to the preparation of lactone, piperidine, tetrazole and oxazole.