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1.
Mater Horiz ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38511304

RESUMO

A key challenge in designing single-atom catalysts (SACs) with multiple and synergistic functions is to optimize their structure across different scales, as each scale determines specific material properties. We advance the concept of a comprehensive optimization of SACs across different levels of scale, from atomic, microscopic to mesoscopic scales, based on interfacial kinetics control on the coupled metal-dissolution/polymer-growth process in SAC synthesis. This approach enables us to manipulate the multilevel interior morphologies of SACs, such as highly porous, hollow, and double-shelled structures, as well as the exterior morphologies inherited from the metal oxide precursors. The atomic environment around the metal centers can be flexibly adjusted during the dynamic metal-oxide consumption and metal-polymer formation. We show the versatility of this approach using mono- or bi-metallic oxides to access SACs with rich microporosity, tunable mesoscopic structures and atomic coordinating compositions of oxygen and nitrogen in the first coordination-shell. The structures at each level collectively optimize the electronic and geometric structure of the exposed single-atom sites and lower the surface *O formation barriers for efficient and selective peroxidase-type reaction. The unique spatial geometric configuration of the edge-hosted active centers further improves substrate accessibility and substrate-to-catalyst hydrogen overflow due to tunable structural heterogeneity at mesoscopic scales. This strategy opens up new possibilities for engineering more multilevel structures and offers a unique and comprehensive perspective on the design principles of SACs.

2.
J Child Orthop ; 17(4): 306-314, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37565002

RESUMO

Purpose: To evaluate the residual acetabular dysplasia in Graf type II hips after Pavlik harness treatment with a radiographic follow-up at 2 years of age. Methods: We retrospectively reviewed the developmental dysplasia of the hip patients who were treated with the Pavlik harness between March 2018 and February 2022. Patients with Graf type II hip dysplasia who had at least one radiographic follow-up after 2 years of age were included. The following information, sex, laterality, affected side, age at harness initiation, treatment duration, α angle, and the morphology of bony roof, was collected and studied. We evaluated the radiographic acetabular index at the last follow-up and defined the value of greater than 2 standard deviations as residual acetabular dysplasia. Results: A total of 33 patients (53 hips) met the criteria. The mean initial α angle was 53.4°; the mean age at Pavlik harness initiation was 10.9 weeks. The mean treatment duration was 10 weeks. The mean α angle at the last ultrasound follow-up was 64.9°. The mean age of the last radiographic follow-up was 2.6 years, and 26 hips had a residual acetabular dysplasia with acetabular indexes greater than 2 standard deviations above the mean. The morphology of the acetabular bony rim (odds ratio = 4.333, P = 0.029) and age of initial treatment <12 weeks (odds ratio = 7.113, P = 0.014) were seen as significant predictors for a higher acetabular index more than 2 years of age. Conclusions: A notable incidence of residual acetabular dysplasia after Pavlik harness treatment in Graf type II hips, wherein the acetabular bony roof with a blunt rim at the end of treatment and initial age after 12 weeks were independent predictors associated with residual acetabular dysplasia. Levels of evidence: Therapeutic studies, IV.

3.
Foods ; 12(15)2023 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-37569173

RESUMO

Atractylodis rhizoma (AR) is an herb and food source with great economic, medicinal, and ecological value. Atractylodes chinensis (DC.) Koidz. (AC) and Atractylodes lancea (Thunb.) DC. (AL) are its two botanical sources. The commercial fraud of AR adulterated with Atractylodes japonica Koidz. ex Kitam (AJ) frequently occurs in pursuit of higher profit. To quickly determine the content of adulteration in AC and AL powder, two spectroscopic techniques, near-infrared spectroscopy (NIRS) and hyperspectral imaging (HSI), were introduced. The partial least squares regression (PLSR) algorithm was selected for predictive modeling of AR adulteration levels. Preprocessing and feature variable extraction were used to optimize the prediction model. Then data and image feature fusions were developed to obtain the best predictive model. The results showed that if only single-spectral techniques were considered, NIRS was more suitable for both tasks than HSI techniques. In addition, by comparing the models built after the data fusion of NIRS and HSI with those built by the single spectrum, we found that the mid-level fusion strategy obtained the best models in both tasks. On this basis, combined with the color-texture features, the prediction ability of the model was further optimized. Among them, for the adulteration level prediction task of AC, the best strategy was combining MLF data (at CARS level) and color-texture features (C-TF), at which time the R2T, RMSET, R2P, and RMSEP were 99.85%, 1.25%, 98.61%, and 5.06%, respectively. For AL, the best approach was combining MLF data (at SPA level) and C-TF, with the highest R2T (99.92%) and R2P (99.00%), as well as the lowest RMSET (1.16%) and RMSEP (2.16%). Therefore, combining data and image features from NIRS and HSI is a potential strategy to predict the adulteration content quickly, non-destructively, and accurately.

4.
Helicobacter ; 28(4): e12984, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37186092

RESUMO

PURPOSE: To characterize the serum metabolism in patients with Helicobacter pylori-positive and H. pylori-negative gastritis. METHODS: Clinical data and serum gastric function parameters, PGI (pepsinogen I), PGII, PGR (PGI/II), and G-17 (gastrin-17) of 117 patients with chronic gastritis were collected, including 57 H. pylori positive and 60 H. pylori negative subjects. Twenty cases in each group were randomly selected to collect intestinal mucosa specimens and serum samples. The gut microbiota profiles were generated by 16S rRNA gene sequencing, and the serum metabolites were analyzed by a targeted metabolomics approach based on liquid chromatography-mass spectrometry (LC-MS) technology. RESULTS: Altered expression of 20 metabolites, including isovaleric acid, was detected in patients with HPAG. Some taxa of Bacteroides, Fusobacterium, and Prevotella in the gut microbiota showed significant correlations with differentially expressed metabolites between H. pylori positive and H. pylori negative individuals. As a result, an H. pylori-gut microbiota-metabolism (HGM) axis was proposed. CONCLUSION: Helicobacter pylori infection may influence the progression of mucosal diseases and the emergence of other complications in the host by altering the gut microbiota, and thus affecting the host serum metabolism.


Assuntos
Gastrite , Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/microbiologia , RNA Ribossômico 16S/genética , Gastrite/microbiologia , Mucosa Gástrica/microbiologia , Inflamação
5.
Chin Herb Med ; 15(1): 57-62, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36875427

RESUMO

Objective: The content of saikosaponins in genus Bupleurum is increased with numbers of lateral root, but the genetic mechanisms are largely unknown. This study aims to identify the heme oxygenase (HO) gene family members of B. chinense and B. scorzonerifolium, and assess their role in the root development in Bupleurum. Methods: The gene sequences of HO family were selected from iso-seq full-length transcriptome data of B. chinense and B. scorzonerifolium, and were analyzed in physicochemical properties, conserved domains, motifs and phylogenetic relationship. In addition, the expression patterns of HO gene in different parts of roots were compared via transcriptome sequencing and qRT-PCR in the two species. Results: Five Bupleurum HO genes (BcHO1-BcHO5) belonging to the HO1 subfamily were identified from the transcriptome data, whereas the HO2 subfamily member was not identified. The expression levels of BcHO1 and BcHO2 were significantly higher than those of other three HO members in the transcriptome analysis. In addition, the expression profile of BcHO1 showed consistency with lateral root development in B. chinense and B. scorzonerifolium. Conclusion: Hos might participate in the auxin-induced morphogenesis of lateral roots. The yield of saikosaponin may be improved by manipulating expression of these genes.

6.
Medicine (Baltimore) ; 102(9): e33143, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36862864

RESUMO

Among all cancer patient's lung cancer is the leading cause of death. Prognostic biomarkers continue to be investigated for the detection and stratification of lung cancer for clinical use. The DNA-dependent protein kinase is involved in mechanisms of DNA damage repair. Deregulation and overexpression of DNA-dependent protein kinase is associated with poor prognosis in various tumor entities. In this study, we investigated the expression of DNA-dependent protein kinase in relation to clinicopathological features and overall survival in patients with lung cancer. By immunohistochemistry, expression of DNA-dependent protein kinase was analyzed in 205 cases of lung cancer; 95 cases of adenocarcinoma, 83 cases of squamous cell lung carcinoma and 27 cases of small cell lung cancer and correlated with clinicopathological characteristics as well as patient's overall survival. In patients with adenocarcinoma, a significant correlation between strong expression of DNA-dependent protein kinase and worse overall survival was found. No significant association was observed in patients with squamous cell lung carcinoma and small cell lung cancer. Strong detection of DNA-dependent protein kinase expression was most evident in small cell lung cancer (81.48 %), followed by squamous cell lung carcinoma (62.65 %) and adenocarcinoma (61.05 %). In our study, expression of DNA-dependent protein kinase was associated with poor overall survival in patients with adenocarcinoma. DNA-dependent protein kinase could serve as a new prognostic biomarker.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Proteína Quinase Ativada por DNA , Prognóstico , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , DNA
7.
Cancers (Basel) ; 15(5)2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36900379

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers. Given the currently limited therapeutic options, the definition of molecular subgroups with the development of tailored therapies remains the most promising strategy. Patients with high-level gene amplification of urokinase plasminogen activator receptor (uPAR/PLAUR) have an inferior prognosis. We analyzed the uPAR function in PDAC to understand this understudied PDAC subgroup's biology better. METHODS: A total of 67 PDAC samples with clinical follow-up and TCGA gene expression data from 316 patients were used for prognostic correlations. Gene silencing by CRISPR/Cas9, as well as transfection of uPAR and mutated KRAS, were used in PDAC cell lines (AsPC-1, PANC-1, BxPC3) treated with gemcitabine to study the impact of these two molecules on cellular function and chemoresponse. HNF1A and KRT81 were surrogate markers for the exocrine-like and quasi-mesenchymal subgroup of PDAC, respectively. RESULTS: High levels of uPAR were correlated with significantly shorter survival in PDAC, especially in the subgroup of HNF1A-positive exocrine-like tumors. uPAR knockout by CRISPR/Cas9 resulted in activation of FAK, CDC42, and p38, upregulation of epithelial makers, decreased cell growth and motility, and resistance against gemcitabine that could be reversed by re-expression of uPAR. Silencing of KRAS in AsPC1 using siRNAs reduced uPAR levels significantly, and transfection of mutated KRAS in BxPC-3 cells rendered the cell more mesenchymal and increased sensitivity towards gemcitabine. CONCLUSIONS: Activation of uPAR is a potent negative prognostic factor in PDAC. uPAR and KRAS cooperate in switching the tumor from a dormant epithelial to an active mesenchymal state, which likely explains the poor prognosis of PDAC with high uPAR. At the same time, the active mesenchymal state is more vulnerable to gemcitabine. Strategies targeting either KRAS or uPAR should consider this potential tumor-escape mechanism.

8.
Life (Basel) ; 13(2)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36836920

RESUMO

Bupleurum chinense DC. is a well-known traditional Chinese medicinal plant that produces saikosaponins (SSs), which possess hepatoprotective, antipyretic, and anti-inflammatory activities. Methyl jasmonate (MeJA) is a signalling phytohormone that can increase the accumulation of SSs in the root of Bupleurum plants. However, the molecular understanding of MeJA-mediated SS biosynthesis is not clear. Therefore, it is necessary to explore the molecular mechanism underlying the response of B. chinense DC. to MeJA in roots. In this study, we performed comparative transcriptome analysis of B. chinense DC. roots with different MeJA treatment times. In total, 104,057 unigenes were identified, of which 4053 were differentially expressed genes (DEGs). Most of the DEGs were downregulated after MeJA treatment, and GO enrichment analysis showed that they were mainly related to biological processes involved in stress responses and development. A total of 88 DEGs encoding enzymes known to be involved in the SS synthesis pathway were found, and most were significantly downregulated within 24 h. Based on the DEGs, 99 transcription factors (TFs) belonging to the AP2/ERF, WRKY, bZIP, ZFP, and bHLH families with different expression patterns were also identified. Further integrated analysis indicated that 20 DEGs involved in the SS synthesis pathway and 12 DEGs encoding TFs presented strong correlations with the SS contents, and these DEGs may be critical for the biosynthesis and regulation of SSs. These findings will be critical for further study of the response of B. chinense DC. to MeJA for SS biosynthesis.

9.
One Health ; 16: 100481, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36683960

RESUMO

The rhizosphere is an extremely important component of the "one health" scenario by linking the soil microbiome and plants, in which the potential enrichment of antibiotic resistance genes (ARGs) might ultimately flow into the human food chain. Despite the increased occurrence of soil-borne diseases, which can lead to increased use of pesticides and antibiotic-producing biocontrol agents, the understanding of the dynamics of ARG spread in the rhizosphere is largely overlooked. Here, tomato seedlings grown in soils conducive and suppressive to the pathogen Ralstonia solanacearum were selected as a model to investigate ARG spread in the rhizosphere with and without pathogen invasion. Metagenomics data revealed that R. solanacearum invasion increased the density of ARGs and mobile genetic elements (MGEs). Although we found ARGs originating from human pathogenic bacteria in both soils, the enrichment was alleviated in the suppressive soil. In summary, the suppressive soil hindered ARG spread through pathogen suppression and had a lower number of taxa carrying antibiotic resistance.

10.
Plant Biotechnol Rep ; 17(2): 159-169, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35873882

RESUMO

Bupleurum chinense DC is an important medicinal plant with many active ingredients that are used for the treatment of different types of diseases and valued in pharmaceutical markets. In vitro shoot regeneration can efficiently contribute to the improvement of B. chinense. In the present study, we investigated the effects of the explant type and plant growth regulators (PGRs) on embryogenic callus induction and plant regeneration in B. chinense. Our investigation demonstrated that 2 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) combined with 1 mg/L thidiazuron (TDZ) played a major role in promoting callus induction from leaf, hypocotyl and stem 2 explants, whereas the most effective treatment for stem 1 callus formation was Murashige and Skoog (MS) medium supplemented with 1 mg/L 2,4-D, 0.5 mg/L 6-benzyladenine (BA) and 0.5 mg/L kinetin (Kin). The highest shoot regeneration rate (57.14%) was obtained from hypocotyl-induced calli in MS medium with 0.5 mg/L Kin after 12 weeks of cultivation. This regeneration protocol can be used in large-scale cultivation and may be useful for future genetic modifications of B. chinense .

11.
J Plant Biochem Biotechnol ; 32(2): 284-295, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36160316

RESUMO

Bupleurum chinense DC. is a commonly used plant in traditional Chinese medicine, and saikosaponins(SSs) are the main active oleanane-typetriterpene saponins in B. chinense. ß-Amyrin synthase (ß-AS) is an important enzyme in oleanane-type triterpenoid saponin synthesis, but its role in saikosaponin synthesis has rarely been studied. Here, the putative ß-AS gene BcBAS1(Accession No.ON890382) selected according to metabolomic and transcriptomic analyses was cloned and functionally characterized by heterologous expression in Escherichia coli and Pichia pastoris, and its subcellular localization and expression patterns were examined. The molecular weight of the BcBAS1 recombinant protein was approximately 87 kDa, and this protein could catalyse the production of ß-amyrin, the precursor of SSs. Furthermore, BcBAS1 was located in the cytosol, and relative expression in four tissues of the four genotypes was positively correlated with SSa and SSd contents. Our results indicate that BcBAS1 is a ß-AS gene and may play an important role in saikosaponin biosynthesis and regulation. This study sheds light on the role of ß-AS genes in the synthesis of SSs and provides insights for the metabolic engineering of SSs.

12.
Genes (Basel) ; 13(12)2022 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-36553505

RESUMO

Bupleurum falcatum L. is frequently used in traditional herbal medicine in Asia. Saikosaponins (SSs) are the main bioactive ingredients of B. falcatum, but the biosynthetic pathway of SSs is unclear, and the biosynthesis of species-specific phytometabolites is little known. Here we resolved the transcriptome profiles of B. falcatum to identify candidate genes that might be involved in the biosynthesis of SSs. By isoform sequencing (Iso-Seq) analyses of the whole plant, a total of 26.98 Gb of nucleotides were obtained and 124,188 unigenes were identified, and 81,594 unigenes were successfully annotated. A total of 1033 unigenes of 20 families related to the mevalonate (MVA) pathway and methylerythritol phosphate (MEP) pathway of the SS biosynthetic pathway were identified. The WGCNA (weighted gene co-expression network analysis) of these unigenes revealed that only the co-expression module of MEmagenta, which contained 343 unigenes, was highly correlated with the biosynthesis of SSs. Comparing differentially expressed gene analysis and the WGCNA indicated that 130 out of 343 genes of the MEmagenta module exhibited differential expression levels, and genes with the most "hubness" within this module were predicted. Manipulation of these genes might improve the biosynthesis of SSs.


Assuntos
Saponinas , Triterpenos , Saponinas/análise , Saponinas/biossíntese , Transcriptoma , Triterpenos/análise , Triterpenos/metabolismo , Bupleurum/metabolismo
13.
Hepatol Commun ; 6(12): 3563-3577, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36321403

RESUMO

Hepatocellular carcinoma (HCC) is a highly invasive malignancy. Recently, GATOR1 (Gap Activity TOward Rags 1) complexes have been shown to play an important role in regulating tumor growth. NPRL2 is a critical component of the GATOR1 complex. Therefore, this study used NPRL2 knockdown to investigate how GATORC1 regulates the prognosis and development of HCC via the mammalian target of rapamycin (mTOR) and autophagy signaling pathways. We established HepG2 cells with NPRL2 knockdown using small interfering RNA (siRNA) and short hairpin RNA (shRNA) systems. The siRNA-mediated and shRNA-mediated NPRL2 down-regulation significantly reduced the expression of NPRL2 and two other GATPOR1 complex components, NPRL3 and DEPDC5, in HepG2 cells; furthermore, the efficient down-regulation of NPRL2 protein expression by both the shRNA and siRNA systems enhanced the proliferation, migration, and colony formation in vitro. Additionally, the NPRL2 down-regulation significantly increased HCC growth in the subcutaneous and orthotopic xenograft mouse models. The NPRL2 down-regulation increased the Rag GTPases and mTOR activation and inhibited autophagy in vitro and in vivo. Moreover, the NPRL2 level in the tumors was significantly associated with mortality, recurrence, the serum alpha fetoprotein level, the tumor size, the American Joint Committee on Cancer stage, and the Barcelona Clinic Liver Cancer stage. Low NPRL2, NPRL3, DEPDC5, and LC3, and high p62 and mTOR protein expression in the tumors was significantly associated with disease-free survival and overall survival in 300 patients with HCC after surgical resection. Conclusion: The efficient down-regulation of NPRL2 significantly increased HCC proliferation, migration, and colony formation in vitro, and increased HCC growth in vivo. Low NPRL2 protein expression in the tumors was closely correlated with poorer clinical outcomes in patients with HCC. These results provide a mechanistic understanding of HCC and aid the development of treatments for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/genética , RNA Interferente Pequeno , Regulação para Baixo , Neoplasias Hepáticas/genética , Serina-Treonina Quinases TOR/genética , Proteínas Ativadoras de GTPase/genética , Autofagia/genética , Mamíferos/genética , Proteínas Supressoras de Tumor/genética
14.
Oxid Med Cell Longev ; 2022: 4320809, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246404

RESUMO

Background: Cancer-associated fibroblasts (CAFs) within the tumor microenvironment are key players in tumorigenesis and tumor development. Nevertheless, the regulatory mechanisms of CAFs on lung squamous cell carcinoma- (LUSC-) associated remain poorly elucidated. Methods: The microarray dataset GSE22874, containing 30 specimens of primary culture of normal fibroblasts (NFs) and 8 specimens of cancer-associated fibroblasts (CAFs) samples derived from LUSC, was retrieved from the Gene Expression Omnibus (GEO) database and then calculated by using the R language (limma package) to identify differentially expressed genes (DEGs). CAF-conditioned medium (CAF-CM) was collected and used to culture LUSC cells, followed by assessment of cell proliferation, apoptosis, and oxidative stress levels by using CCK-8, annexin V-FITC/PI double staining and ELISA assays. Subsequently, COL10A1 was knocked down in CAFs to assess the role of COL10A1 in CAF regulation of LUSC behavior. Bioinformatics online analysis and MeRIP were applied to predict and test the m6A modification of COL10A1 mRNA and the regulatory relationship with METTL3. Rescue experiments were next performed to explore the effects of METTL3 and COL10A1 in CAFs on LUSC cell proliferation, apoptosis, and oxidative stress. LUSC tumor cells with or without (COL10A1-silenced) CAFs were subcutaneously inoculated in nude mice to evaluate the effect of COL10A1 in CAFs on LUSC tumor growth. Results: Elevated expression of COL10A1 was found in LUSC-derived CAFs by GSE22874 dataset analysis. We discovered that COL10A1 and METTL3 was expressed in both LUSC cells and matched CAFs, while COL10A1 expression was prominently higher in CAFs than in LUSC cells. CAF-CM memorably encouraged LUSC cell proliferation and suppressed apoptosis-induced oxidative stress, which was reversed by interfering with COL10A1 expression in CAFs, suggesting that COL10A1 might be secreted by CAFs into the culture medium to exert its effects inside LUSC cells. Global m6A modification was decreased in METTL3 knocked down CAFs. M6A modification, expression levels, and stability of COL10A1 mRNA were impaired upon METTL3 knockdown in CAFs. Overexpression of COL10A1 in CAFs partially reversed the effect of METTL3 knockdown on the malignant behavior of LUSC cells. In vivo studies confirmed that CAFs accelerated LUSC tumor growth, and this effect was counteracted by COL10A1 silencing. Conclusions: COL10A1 secreted by CAFs could facilitate LUSC cell proliferation and repress apoptosis-induced oxidative stress, and the mechanism was due to elevated expression mediated by METTL3 promoting its mRNA m6A modification, thereby accelerating tumor growth.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Animais , Apoptose/genética , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Colágeno Tipo X , Meios de Cultivo Condicionados/metabolismo , Fibroblastos/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Metilação , Metiltransferases , Camundongos , Camundongos Nus , Estresse Oxidativo , RNA Mensageiro/metabolismo , Sincalida/metabolismo
15.
Metabolites ; 12(7)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35888776

RESUMO

Activating KRAS mutations occur in about 30% of pulmonary adenocarcinoma (AC) cases and the discovery of specific inhibitors of G12C-mutated KRAS has considerably improved the prognosis for a subgroup of about 14% of non-small cell lung cancer (NSCLC) patients. However, even in patients with a KRAS G12C mutation, the overall response rate only reaches about 40% and mutations other than G12C still cannot be targeted. Despite the fact that one-carbon metabolism (1CM) and epigenetic regulation are known to be dysregulated by aberrant KRAS activity, we still lack evidence that co-treatment with drugs that regulate these factors might ameliorate response rates and patient prognosis. In this study, we show a direct dependency of Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) and Enhancer of Zeste Homolog 2 (EZH2) expression on mutationally activated KRAS and their prognostic relevance in KRAS-mutated AC. We show that aberrant KRAS activity generates a vulnerability of AC cancer cell lines to both MTHFD2 and EZH2 inhibitors. Importantly, co-inhibition of both factors was synergistically effective and comparable to KRASG12C inhibition alone, paving the way for their use in a therapeutic approach for NSCLC cancer patients.

16.
New Phytol ; 235(4): 1558-1574, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35569105

RESUMO

Stimulating the development of soil suppressiveness against certain pathogens represents a sustainable solution toward reducing pesticide use in agriculture. However, understanding the dynamics of suppressiveness and the mechanisms leading to pathogen control remain largely elusive. Here, we investigated the mechanisms used by the rhizosphere microbiome induces bacterial wilt disease suppression in a long-term field experiment where continuous application of bio-organic fertilizers (BFs) triggered disease suppressiveness when compared to chemical fertilizer application. We further demonstrated in a glasshouse experiment that the suppressiveness of the rhizosphere bacterial communities was triggered mainly by changes in community composition rather than only by the abundance of the introduced biocontrol strain. Metagenomics approaches revealed that members of the families Sphingomonadaceae and Xanthomonadaceae with the ability to produce secondary metabolites were enriched in the BF plant rhizosphere but only upon pathogen invasion. We experimentally validated this observation by inoculating bacterial isolates belonging to the families Sphingomonadaceae and Xanthomonadaceae into conducive soil, which led to a significant reduction in pathogen abundance and increase in nonribosomal peptide synthetase gene abundance. We conclude that priming of the soil microbiome with BF amendment fostered reactive bacterial communities in the rhizosphere of tomato plants in response to biotic disturbance.


Assuntos
Ralstonia solanacearum , Bactérias/genética , Fertilizantes , Doenças das Plantas/microbiologia , Rizosfera , Solo/química , Microbiologia do Solo
17.
Dalton Trans ; 51(7): 2932-2942, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35107109

RESUMO

Exploiting high color purity phosphors is a core problem in the development of phosphor conversion light-emitting diodes (pc-LEDs) for display devices. Eu3+-activated BaTi(BO3)2 (BTB) red-emitting phosphors were first synthesized via a solid-state reaction at low temperature and alkali metal ions Na+ were co-doped in BTB:xEu3+ to improve the luminescence properties. The occupation of the Eu3+ ions and the enhancement principles of the Na+ ions and their effect on the photoluminescence properties of the BTB:xEu3+ phosphors are discussed in detail. The BTB:xEu3+,Na+ system demonstrated a strong thermal stability (68.4% at 150 °C), low color temperature (about 1940-1950 K) and high color purity (almost 90%). Furthermore, the prototype LED device can emit a bright white light, has a stable luminous efficiency and color rendering index, and the color gamut reaches 115.5% of the NTSC standard. Therefore, the BTB:xEu3+,Na+ series phosphors provide a better choice for the development of lighting and display devices with a wide color gamut.

18.
Medicine (Baltimore) ; 101(6): e28814, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35147120

RESUMO

ABSTRACT: Lung cancer remains the worldwide leading cause of cancer-related death. Currently, prognostic biomarkers for the detection and stratification of lung cancer are being investigated for clinical use. The surface protein cluster of differentiation 49b (CD49b) plays an important role in promoting cell proliferation and invasion in different tumor entities and blocking CD49b improved the tumor immune response. Overexpression of CD49b has been associated with unfavorable survival rates in several malignant tumor entities, such as prostate cancer, gastric cancer and colon cancer. Therefore, we aimed to analyze the protein expression of CD49b in patients with different types of lung cancer and additionally to identify the influence of CD49b on clinicopathological characteristics and overall survival.Expression levels of CD49b were retrospective analyzed by immunohistochemistry in 92 cases of pulmonary adenocarcinoma (AC), 85 cases of squamous cell lung carcinoma (SQCLC) and 32 cases of small cell lung cancer (SCLC) and correlated with clinicopathological characteristics and patients' overall survival.A strong expression of CD49b was most seen in SQCLC (78%), followed by AC (48%) and SCLC (9%). All patients combined, strong expression of CD49b correlated significantly with poorer overall survival. However, an increased expression of CD49b correlated significantly with a poorer survival rate only in SQCLC. In AC and SCLC, no significant correlation could be demonstrated in this regard.In our study, CD49b expression was associated with poor overall survival in patients with SQCLC. Accordingly, CD49b could serve as a new prognostic biomarker and, moreover, be a potential new drug target in SQCLC.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Carcinoma de Células Escamosas/metabolismo , Integrina alfa2/metabolismo , Neoplasias Pulmonares/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Diferenciação Celular , Feminino , Humanos , Integrina alfa2/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/mortalidade , Taxa de Sobrevida
19.
Inorg Chem ; 61(5): 2463-2475, 2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35073687

RESUMO

Functional materials with stable and adjustable luminescence have recently become a research hotspot for their broad application prospects. Tunable luminescence can be realized by the doping of hetero-valent europium ions. High-temperature hydrogen atmosphere reduction is required in the traditional preparation of Eu2+-doped phosphors. Herein, an anoxic molten-salt medium environment was established to form oxygen vacancy defects in the reaction system and induce the self-reduction of Eu3+ ions to obtain Eu2+ ions. X-ray photoelectron spectroscopy (XPS) results confirm the existence of Eu2+ and Eu3+ ions in the samples, and the fluorescence spectrum shows that hetero-valent Eu ions can synergistically emit light effectively. Under 266 nm ultraviolet light excitation, the white light emission was successfully realized for a Ba2InTaO6:Eu phosphor by different emission combinations of Eu3+ and Eu2+ ions. In addition, the Ba2InTaO6:Eu phosphor exhibits adjustable luminescence from greenish-yellow to red exciting at 390-490 nm, which has superior stability in a high-temperature and high-humidity environment. Therefore, it is very promising that Ba2InTaO6:Eu will be used as multi-color functional materials in many fields such as communication encryption and colorful decoration.

20.
Angew Chem Int Ed Engl ; 60(48): 25296-25301, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34525249

RESUMO

Atomically dispersed metal-nitrogen sites show great prospect for the oxygen reduction reaction (ORR), whereas the unsatisfactory adsorption-desorption behaviors of oxygenated intermediates on the metal centers impede improvement of the ORR performance. We propose a new conceptual strategy of introducing sacrificial bonds to remold the local coordination of Fe-Nx sites, via controlling the dynamic transformation of the Fe-S bonds in the Fe-N-C single-atom catalyst. Spectroscopic and theoretical results reveal that the selective cleavage of the sacrificial Fe-S bonds induces the incorporation of the electron-withdrawing oxidized sulfur on the Fe centers. The newly functionalized moieties endow the catalyst with superior ORR activity and remarkable stability, owing to the reduced electron localization around the Fe centers facilitating the desorption of ORR intermediates. These findings provide a unique perspective for precisely controlling the coordination structure of single-atom materials to optimize their activity.

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