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Communication between myeloid cells and epithelium plays critical role in maintaining intestinal epithelial barrier integrity. Myeloid cells interact with intestinal epithelial cells (IECs) by producing various mediators; however, the molecules mediating their crosstalk remain incompletely understood. Here, we report that deficiency of angiogenin (Ang) in mouse myeloid cells caused impairment of epithelial barrier integrity, leading to high susceptibility to DSS-induced colitis. Mechanistically, myeloid cell-derived angiogenin promoted IEC survival and proliferation through plexin-B2-mediated production of tRNA-derived stress-induced small RNA (tiRNA) and transcription of ribosomal RNA (rRNA), respectively. Moreover, treatment with recombinant angiogenin significantly attenuated the severity of experimental colitis. In human samples, the expression of angiogenin was significantly down-regulated in patients with inflammatory bowel disease (IBD). Collectively, we identified, for the first time to our knowledge, a novel mediator of myeloid cell-IEC crosstalk in maintaining epithelial barrier integrity, suggesting that angiogenin may serve as a new preventive agent and therapeutic target for IBD.
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Mucosa Intestinal/metabolismo , Células Mieloides/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Ribonuclease Pancreático/metabolismo , Transdução de Sinais , Animais , Comunicação Celular/genética , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Sulfato de Dextrana/toxicidade , Humanos , Mucosa Intestinal/patologia , Camundongos , Camundongos Knockout , Células Mieloides/patologia , Proteínas do Tecido Nervoso/genética , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Ribonuclease Pancreático/genéticaRESUMO
BACKGROUND: Epidemiological and experimental studies suggest that preeclampsia has a negative impact on maternity and offspring health. Previous studies report that dysregulation in utero-environment increases risk for elderly disease such as cardiovascular disease. However, the underlying mechanisms remain elusive. Specific microRNAs (miRNAs) are packaged in exosomes may regulate microvascular dysfunction in offspring of mothers with preeclampsia. The present study aimed to identify the differential expression profiles of microRNAs in the serum exosomes between patients with preeclampsia and normal pregnancies. METHODS: A comprehensive miRNA sequence-based approach was performed to compare exosomes carry miRNAs (Exo-miRNAs) expression levels in umbilical serum between normal and preeclampsia patients. Exosomes were isolated using the ExoQuick precipitation kit. Serum exosomes were then viewed under electron microscopy, and their characteristics determined by western blotting and nanoparticle-tracking analysis. Illumina platform was used to perform sequencing. Bioinformatics analysis was used to explore differentially expressed Exo-miRNAs in umbilical serum. RESULTS: Based on sequence similarity, 1733 known miRNAs were retrieved. Furthermore, 157 mature miRNAs in serum exosomes were significantly differential expressed between PE and those control groups (P<0.05, log2|FC| > 1). Out, of the 157 miRNAs, 96 were upregulated miRNAs whereas 61 miRNAs were downregulated. The 157 differentially expressed miRNAs targeted 51,424 differentially expressed genes. Functional analysis through KEGG pathway and Gene Ontology results uncovered that target genes of miRNAs with differential expression were significantly linked to several pathways and biological processes. CONCLUSION: The findings of this study showed differential expression of umbilical serum Exo-miRNAs in normal compared with PE patients, implying that these Exo-miRNAs may associate with microvascular dysfunction in offspring of mothers with preeclampsia.
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Exossomos/metabolismo , Sangue Fetal/metabolismo , MicroRNAs/metabolismo , Pré-Eclâmpsia/sangue , Regulação para Baixo , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Gravidez , Análise de Sequência de RNA , Transdução de Sinais , Regulação para CimaRESUMO
BACKGROUND: Ectopic thymic carcinoma (TC) is an extremely rare disease with a poor prognosis. The main treatment for early TC is surgery, although an effective treatment for advanced TC is lacking. METHODS: We present the case of a 61-year-old man with advanced posterior mediastinum thymic squamous cell carcinoma. Amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) analysis was used to investigate the molecular and mutational characteristics of this tumour. RESULTS: After chemotherapy and radiotherapy, the tumour showed disease progression. Immunohistochemistry revealed that the tumour was positive for CD117 (specific for primary TC), CK19, CD56 and Ki67. ARMS-PCR analysis revealed an EGFR exon 19 deletion in the patient. The patient subsequently received icotinib treatment and achieved complete remission for 3 years. CONCLUSIONS: This case report suggests that tyrosine kinase inhibitors are a potential treatment strategy for patients with TC harbouring EGFR alterations.
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Éteres de Coroa/uso terapêutico , Quinazolinas/uso terapêutico , Timoma/tratamento farmacológico , Neoplasias do Timo/tratamento farmacológico , Antineoplásicos/uso terapêutico , Receptores ErbB/genética , Éxons , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/antagonistas & inibidores , Deleção de Sequência , Timoma/diagnóstico por imagem , Timoma/genética , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/genéticaRESUMO
BACKGROUND: Preeclampsia and gestational hypertension can cause vascular function impairment in offspring. In our previous work, we described the protein expression profiles of umbilical artery tissues from patients with preeclampsia. METHODS: To gain insights into the mechanisms of vascular dysfunction in adult rats born to preeclamptic dams, we analyzed thoracic aorta tissues by using iTRAQ isobaric tags and 2D nano LC-MS/MS. RESULTS: By using the iTRAQ method, we analyzed 1825 proteins, of which 106 showed significantly different expression in the thoracic aortic. Ingenuity pathway analysis (IPA) showed that the majority of differentially expressed proteins (DEPs) were associated with cardiovascular function. Further analysis indicated that glucose-6-phosphate dehydrogenase (G6PD), which is inhibited by miR-423-5p and activated by TP53, had the strongest effect on cardiovascular function. The expression of G6PD was upregulated in thoracic aorta tissues, as confirmed by Western blotting. The expression of two other vascular function-related proteins, cysteine- and glycine-rich protein 2 (CSRP2) and tubulin alpha-4 A (TUBA4A), was upregulated, as demonstrated by mass spectrometry (MS). CONCLUSIONS: Although the results require further functional validation, these data provide novel findings related to vascular function impairment in the adult offspring of preeclamptic mothers.
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OBJECTIVE: Colorectal cancer is one of the most prevalent types of cancer worldwide. Right-sided and left-sided colorectal cancer (RCC and LCC) patients respond differently to treatment. We aimed to identify the different mutational profile between RCC and LCC and provided evidence for future precision therapy. METHODS: A total of 630 Chinese colorectal cancer patients, including 467 (74.1%) LCC and 163 (25.9%) RCC, were enrolled in this cohort. Both formalin-fixed paraffin-embedded tumor tissues and matching blood samples were collected and deep sequenced targeting 450 cancer genes for genomic alteration analysis. Tumor mutational burden was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher's exact test. RESULTS: The most common mutated genes were TP53 (77.0%), APC (71.7%), KRAS (50.0%), SMAD4 (19.8%), PIK3CA (18.3%), FBXW7 (17.5%), TCF7L2 (12.5%), SOX9 (11.3%), LRP1B (10.8%), ARID1A (10.3%) and FAT4 (10.3%). The mutation frequencies of TP53 and APC in LCC were significantly higher than that of RCC, while the mutation frequency of PIK3CA was lower than that of RCC. Six gene fusions were specifically detected in RCC patients. Colorectal cancer sites were associated with gender (P = 4.15 × 10-5) and tumor differentiation (P = 0.059). In LCC, the gender-associated genes were FAT4, EP300, FAT1, LRP1, ARID1B, AR, FYN and TAF1, while in RCC, they were ARID1A, SMARCA4, LRP1 and GRIN2A. The mutations of 18 genes were associated with tumor differentiation (8 for LCC and 10 for RCC). High tumor mutational burden was more common in RCC. Our results implied more potential targeted drug therapy opportunities for RCC. CONCLUSION: We describe the different molecular characteristics of LCC and RCC. Our result supported a better prognosis of RCC than LCC in Chinese colorectal cancer patients.
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Neoplasias Colorretais/genética , Taxa de Mutação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Cholangiocarcinoma (CCA) is a rare malignant tumor of the biliary system. The heterogeneity of CCA leads to the lack of effective targeted treatment for CCA subtypes. The molecular characteristic of hilar CCA (hCCA) is still unclear. METHODS: A total of 63 hCCA patients were enrolled from Shanghai Eastern Hepatobiliary Surgery Hospital. Formalin-fixed, paraffin-embedded tumor tissues, and matched blood were collected and deep sequencing targeting 450 cancer genes were performed. Tumor mutation burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher's exact test. RESULTS: The most commonly mutated genes were TP53 (51.7%), NF1 and KRAS (20%, for both), SMAD4 (16.7%), FAT3 and FRS2 (13.3%, for both), NF1 (11.7%), and KMT2C, MDM2, and ATM (10%, for each) in hCCA. ARID1A, GATA6, and PREX2 mutations commonly occurred in female and KMT2C mutations mainly occurred in patients under 60 years old. Statistical analysis showed the association between ARID1A mutation and tumor stage (P = 0.041) and between NF1 mutation and high TMB (P = 0.0095). Furthermore, ARID1B mutation was identified to associate with the poor prognosis of Chinese hCCA patients (P = 0.004). CONCLUSION: The mutational characterization of hCCA is different from both extrahepatic CCA and intrahepatic CCA. ARID1B is a potential biomarker for prognosis prediction of Chinese hCCA patients.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , China , Colangiocarcinoma/genética , Feminino , Genômica , Humanos , Pessoa de Meia-Idade , MutaçãoRESUMO
OBJECTIVE: To explore the molecular mechanism of a case where RhD genotyping did not match serological results. METHODS: The serological results of 8 members from two generations of this family were analyzed. And according to Mendelian law of inheritance, RhD genotyping, zygotic type determination and gene sequencing were performed for the family members. RESULTS: The proband and one of her cousins have the same RhD alleles, both of them have a 336-1G>A intron variant RhD allele and a complete RhD deletion allele. The variant alleles are inherited from two of their parents with blood relationship, while the complete-deleted alleles come from the other. 336-1G>A means that the last base G of the second intron of the RhD gene is mutated to A, which leads to a negative RhD serology and a positive genotype in the proband. CONCLUSION: There was a rare 336-1G> A intron variant gene (RhD * 01N.25) in this family, which was a recessive gene relative to the RhD gene and resulted in RhD phenotype negative.
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Sistema do Grupo Sanguíneo Rh-Hr , Alelos , Feminino , Genótipo , Humanos , Íntrons/genética , Linhagem , Fenótipo , Sistema do Grupo Sanguíneo Rh-Hr/genéticaRESUMO
OBJECTIVE: Cholangiocarcinoma (CCA) is a primary malignancy, which is often diagnosed as advanced and inoperable due to the lack of effective biomarkers and poor sensitivity of clinical diagnosis. Here, we aimed to identify the genomic profile of CCA and provided molecular evidence for further biomarker development. METHODS: The formalin-fixed paraffin-embedded and matching blood samples were sequenced by deep sequencing targeting 450 cancer genes and genomic alteration analysis was performed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher's exact test. RESULTS: The most commonly altered genes in this cohort were TP53 (41.27%, 26/63), KRAS (31.75%, 20/63), ARID1A and IDH1 (15.87%, 10/63, for both), SMAD4 (14.29%, 9/63), FGFR2 and BAP1 (12.70%, 8/63, for both), and CDKN2A (11.11%, 7/63). BAP1 mutations were significantly correlated with the CCA subtype. LRP2 mutations were significantly associated with the younger intrahepatic CCA (iCCA) patients, while BAP1 was associated with iCCA patients aged 55-65 years old. BAP1 and LRP2 mutations were associated with TMB. CONCLUSIONS: Most Chinese CCA patients were 50-70 years old. BAP1 and LRP2 mutations were associated with the age of iCCA patients.
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Povo Asiático/genética , Colangiocarcinoma/genética , Genoma Humano , Mutação/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genéticaRESUMO
Metastasis of colorectal cancer (CRC) is the leading cause of CRC-associated mortality. Angiogenin (ANG), a member of the ribonuclease A superfamily, not only activates endothelial cells to induce tumor angiogenesis, but also targets tumor cells to promote cell survival, proliferation and/or migration. However, its clinical significance and underlying mechanism in CRC metastasis are still largely unknown. Here, we reported that ANG was upregulated in CRC tissues and associated with metastasis in CRC patients. We then revealed that ANG enhanced CRC growth and metastasis in both in vitro and in vivo systems. Intriguingly, we characterized a bunch of tRNA-derived stress-induced small RNAs (tiRNAs), produced through ANG cleavage, that was enriched in both CRC tumor tissues and highly metastatic cells, and functioned in ANG-promoted CRC metastasis. Moreover, higher level of a 5'-tiRNA from mature tRNA-Val (5'-tiRNA-Val) was observed in CRC patients and was correlated with tumor metastasis. Taken together, we propose that a novel ANG-tiRNAs-cell migration and invasion regulatory axis promotes CRC metastasis, which might be of potential target for CRC diagnosis and treatment.
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Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , RNA de Transferência/biossíntese , Ribonuclease Pancreático/metabolismo , Regiões 5' não Traduzidas , Animais , Estudos de Casos e Controles , Movimento Celular/fisiologia , Neoplasias do Colo/irrigação sanguínea , Neoplasias do Colo/genética , Técnicas de Inativação de Genes , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Invasividade Neoplásica , Metástase Neoplásica , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , RNA de Transferência/genética , RNA de Transferência/metabolismo , Ribonuclease Pancreático/genética , Regulação para CimaRESUMO
In this paper, a glutathione functionalized gold nanocluster (GSH-AuNCs) was prepared. GSH-AuNCs can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide to produce a blue-green ox-TMB. By using its peroxidase activity and the GSH-AuNCs-TMB-H2O2 system, the visualization of Fe3+ and Cu2+ and the high sensitivity detection of Fe3+ and Cu2+ can be realized according to the change of absorbance value and color of the system. The results showed that the sensitivity of the system to detect Fe3+ and Cu2+ in industrial wastewater reached 1.25 × 10-9 M and 1.25 × 10-10M, respectively. At the same time, the chelating agents NH4F and EDTA · 2Na were introduced to realize the selective detection of the two ions under the coexistence of Fe3+ and Cu2+ ions.
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Ouro , Nanopartículas Metálicas , Colorimetria , Glutationa , Peróxido de Hidrogênio , Limite de DetecçãoRESUMO
We study experimentally the formation of a dual hierarchical jetting pattern in dry dense particle media subjected to the radially divergent shock loadings in a radial Hele-Shaw cell. The distinct internal and external jetting patterns were formed on the internal and external surfaces of a ring at different times, respectively. The former features dozens of radially aligned fine filaments. By contrast, the latter consists of a large number of small spikes. Once the internal jets are fully developed, a novel proportionate growth is observed, in which distinguishable structures of the overall pattern all grow at the same rate until the interaction between the internal and external jets becomes significant, leading to the inversion of the internal jetting pattern. Although the external jetting is found to be an instability of a Rayleigh-Taylor (RT) type, the internal jetting exhibits a much delayed onset and slower early-stage growth compared with the RT instability, indicating different underlying physics.
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Since its domestication from wild rice thousands of years ago, rice has been cultivated largely through transplantation. During transplantation from the nursery to the paddy field, rice seedlings experience transplantation shock which affects their physiology and production. However, the mechanisms underlying transplantation shock and rice adaptation to this shock are largely unknown. Here, we isolated a transplant-sensitive chloroplast-deficient (tsc1) rice mutant that produces albino leaves after transplantation. Blocking light from reaching the juvenile leaves and leaf primordia caused chloroplast deficiencies in transplanted tsc1 seedlings. TSC1 encodes a noncanonical adenosine triphosphate-binding cassette (ABC) transporter homologous to AtNAP14 and is of cyanobacterial origin. We demonstrate that TSC1 controls plastid development in rice under dark conditions, and functions independently of light signaling. However, light rescued the tsc1 mutant phenotype in a spectrum-independent manner. TSC1 was upregulated following transplantation, and modulated the iron and copper levels, thereby regulating prolamellar body formation during the early P4 stage of leaf development. Therefore, TSC1 is indispensable for plastid development in the absence of light, and contributes to adaptation to transplantation shock. Our study provides insight into the regulation of plastid development and establishes a framework for improving recovery from transplantation shock in rice.
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Adaptação Fisiológica , Escuridão , Oryza/fisiologia , Proteínas de Plantas/metabolismo , Plastídeos/metabolismo , Adaptação Fisiológica/genética , Clonagem Molecular , Cobre/metabolismo , Genes de Plantas , Teste de Complementação Genética , Loci Gênicos , Homeostase , Ferro/metabolismo , Mutação/genética , Oryza/genética , Oryza/ultraestrutura , Fenótipo , Folhas de Planta/fisiologia , Brotos de Planta/fisiologia , Plastídeos/ultraestrutura , Estresse FisiológicoRESUMO
Seedling establishment is inhibited on media containing high levels (â¼ 6%) of glucose or fructose. Genetic loci that overcome the inhibition of seedling growth on high sugar have been identified using natural variation analysis and mutant selection, providing insight into sugar signaling pathways. In this study, a quantitative trait locus (QTL) analysis was performed for seedling sensitivity to high sugar in a Col/C24 F2 population of Arabidopsis thaliana. A glucose and fructose-sensing QTL, GSQ11, was mapped through selective genotyping and confirmed in near-isogenic lines in both Col and C24 backgrounds. Allelism tests and transgenic complementation showed that GSQ11 lies within the ANAC060 gene. The Col ANAC060 allele confers sugar insensitivity and was dominant over the sugar-sensitive C24 allele. Genomic and mRNA analyses showed that a single-nucleotide polymorphism (SNP) in Col ANAC060 affects the splicing patterns of ANAC060 such that 20 additional nucleotides are present in the mRNA. The insertion created a stop codon, resulting in a truncated ANAC60 protein lacking the transmembrane domain (TMD) that is present in the C24 ANAC060 protein. The absence of the TMD results in the nuclear localization of ANAC060. The short version of the ANAC060 protein is found in â¼ 12% of natural Arabidopsis accessions. Glucose induces GSQ11/ANAC060 expression in a process that requires abscisic acid (ABA) signaling. Chromatin immunoprecipitation-qPCR and transient expression analysis showed that ABI4 directly binds to the GSQ11/ANAC060 promoter to activate transcription. Interestingly, Col ANAC060 reduced ABA sensitivity and Glc-induced ABA accumulation, and ABI4 expression was also reduced in Col ANAC060 lines. Thus, the sugar-ABA signaling cascade induces ANAC060 expression, but the truncated Col ANAC060 protein attenuates ABA induction and ABA signaling. This negative feedback from nuclear ANAC060 on ABA signaling results in sugar insensitivity.
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Proteínas de Arabidopsis/genética , Locos de Características Quantitativas/genética , Plântula/genética , Transdução de Sinais/genética , Fatores de Transcrição/genética , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/metabolismo , Núcleo Celular/genética , Núcleo Celular/metabolismo , Frutose/metabolismo , Regulação da Expressão Gênica de Plantas , Teste de Complementação Genética , Genótipo , Glucose/metabolismo , Mutação , Fatores de Transcrição/metabolismoRESUMO
Chloroplasts are essential for photosynthesis and play critical roles in plant development. In this study, we characterized the temperature-sensitive chlorophyll-deficient rice mutant tcd5, which develops albino leaves at low temperatures (20 °C) and normal green leaves at high temperatures (32 °C). The development of chloroplasts and etioplasts is impaired in tcd5 plants at 20 °C, and the temperature-sensitive period for the albino phenotype is the P4 stage of leaf development. The development of thylakoid membranes is arrested at the mid-P4 stage in tcd5 plants at 20 °C. We performed positional cloning of TCD5 and then complementation and knock-down experiments, and the results showed that the transcript LOC_Os05g34040.1 from the LOC_Os05g34040 gene corresponded to the tcd5 phenotype. TCD5 encodes a conserved plastid-targeted monooxygenase family protein which has not been previously reported associated with a temperature-sensitive albino phenotype in plants. TCD5 is abundantly expressed in young leaves and immature spikes, and low temperatures increased this expression. The transcription of some genes involved in plastid transcription/translation and photosynthesis varied in the tcd5 mutant. Although the phenotype and temperature dependence of the TCD5 orthologous mutant phenotype were different in rice and Arabidopsis, OsTCD5 could rescue the phenotype of the Arabidopsis mutant, suggesting that TCD5 function is conserved between monocots and dicots.
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Cloroplastos/fisiologia , Genes de Plantas/fisiologia , Oxigenases de Função Mista/fisiologia , Arabidopsis/fisiologia , Western Blotting , Clorofila/metabolismo , Clonagem Molecular , Temperatura Baixa , Eletroforese em Gel de Poliacrilamida , Microscopia Eletrônica de Transmissão , Oxigenases de Função Mista/metabolismo , Oryza/genética , Oryza/metabolismo , Oryza/fisiologia , Filogenia , Folhas de Planta/metabolismo , Plantas Geneticamente Modificadas , Alinhamento de SequênciaRESUMO
In living organisms sugars not only provide energy and carbon skeletons but also act as evolutionarily conserved signaling molecules. The three major soluble sugars in plants are sucrose, glucose, and fructose. Information on plant glucose and sucrose signaling is available, but to date no fructose-specific signaling pathway has been reported. In this study, sugar repression of seedling development was used to study fructose sensitivity in the Landsberg erecta (Ler)/Cape Verde Islands (Cvi) recombinant inbred line population, and eight fructose-sensing quantitative trait loci (QTLs) (FSQ1-8) were mapped. Among them, FSQ6 was confirmed to be a fructose-specific QTL by analyzing near-isogenic lines in which Cvi genomic fragments were introgressed in the Ler background. These results indicate the existence of a fructose-specific signaling pathway in Arabidopsis. Further analysis demonstrated that the FSQ6-associated fructose-signaling pathway functions independently of the hexokinase1 (HXK1) glucose sensor. Remarkably, fructose-specific FSQ6 downstream signaling interacts with abscisic acid (ABA)- and ethylene-signaling pathways, similar to HXK1-dependent glucose signaling. The Cvi allele of FSQ6 acts as a suppressor of fructose signaling. The FSQ6 gene was identified using map-based cloning approach, and FSQ6 was shown to encode the transcription factor gene Arabidopsis NAC (petunia No apical meristem and Arabidopsis transcription activation factor 1, 2 and Cup-shaped cotyledon 2) domain containing protein 89 (ANAC089). The Cvi allele of FSQ6/ANAC089 is a gain-of-function allele caused by a premature stop in the third exon of the gene. The truncated Cvi FSQ6/ANAC089 protein lacks a membrane association domain that is present in ANAC089 proteins from other Arabidopsis accessions. As a result, Cvi FSQ6/ANAC089 is constitutively active as a transcription factor in the nucleus.
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Proteínas de Arabidopsis/fisiologia , Arabidopsis/metabolismo , Frutose/metabolismo , Transdução de Sinais , Fatores de Transcrição/fisiologia , Ácido Abscísico/metabolismo , Etilenos/metabolismo , Frutose/farmacologia , Hexoquinase , Locos de Características Quantitativas , Plântula/efeitos dos fármacosRESUMO
Terrestrial ecosystems have undergone significant changes as a result of climate change, profoundly affecting global carbon and water cycling processes. Notably, the synergistic changes in vegetation carbon use efficiency (CUE) and water use efficiency (WUE) and their response to patterns of climate change over the last 40â¯years are unknown. Therefore, in this study, global vegetation WUE and CUE were inverted using Gross primary productivity (GPP), Net primary productivity (NPP) and total evaporation (ET) data from 1981 to 2019 to reveal their temporal and spatial patterns of change through trend analysis and stability analysis. A stepwise regression algorithm was used to reveal the potential driving law of environmental factors on vegetation WUE and CUE. The results shows that (1) From 1981 to 2019, the global vegetation WUE and CUE showed in a relatively stable state, and the trends of WUE and CUE were -0.00004/year and 0.006â¯g C m-2â¯mm-1/year, respectively; (2) the greening of vegetation was the most important cause of the changes in WUE and CUE, and the driving force of rain and heat conditions on the CUE of vegetation was smaller than that of solar radiation and soil water, the regions where CO2 is the dominant factor affecting CUE and WUE are mainly in the north temperate zone; (3) the region of synergistic growth of WUE and CUE accounts for about 31.38â¯% of the global terrestrial area, and this pattern of change suggests that the global vegetation carbon sink potential is huge, and the popularization of vegetation planting patterns under the synergistic growth of CUE and WUE should be strengthened. The research has shown that vegetation greening is a key factor influencing changes in the WUE and CUE of vegetation, therefore, the implementation of ecological engineering will be an important step in combating climate change.
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Meningioma is a benign tumor with slow growth and long course. However, patients with recurrent malignant meningioma still face a lack of effective treatment. Here, we report a rare case of primary mediastinal malignant meningioma with lung and bone metastases, who benefited from the treatment of apatinib (≥33 months) and anlotinib (until the publication date). Retrospective molecular analysis revealed the frequent amplification of FGF6 in primary and metastatic lesions. Then we constructed the FGF6 over-expressed IOMM-LEE and CH157MN malignant meningioma cell lines, and in vitro and vivo experiments showed that overexpression of FGF6 can promote the proliferation, migration and invasion of malignant meningioma cells. Based on the Western analysis, we revealed that FGF6 can promote the phosphorylation of FGFR, AKT, and ERK1/2, which can be inhibited by anlotinib. Together, we were the first to verify that overexpression of FGF6 promotes the progression of malignant meningiomas by activating FGFR/AKT/ERK1/2 pathway and pointed out that anlotinib may effectively inhibit the disease progression of patients with FGF6 amplification.
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Ovarian metastasis is one of the major causes of treatment failure in patients with gastric cancer (GC). However, the genomic characteristics of ovarian metastasis in GC remain poorly understood. In this study, we enroll 74 GC patients with ovarian metastasis, with 64 having matched primary and metastatic samples. Here, we show a characterization of the mutation landscape of this disease, alongside an investigation into the molecular heterogeneity and pathway mutation enrichments between synchronous and metachronous metastasis. We classify patients into distinct clonal evolution patterns based on the distribution of mutations in paired samples. Notably, the parallel evolution group exhibits the most favorable prognosis. Additionally, by analyzing the differential response to chemotherapy, we identify potential biomarkers, including SALL4, CCDC105, and CLDN18, for predicting the efficacy of paclitaxel treatment. Furthermore, we validate that CLDN18 fusion mutations improve tumor response to paclitaxel treatment in GC with ovarian metastasis in vitro and vivo.
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Biomarcadores Tumorais , Mutação , Neoplasias Ovarianas , Paclitaxel , Neoplasias Gástricas , Paclitaxel/uso terapêutico , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Biomarcadores Tumorais/genética , Claudinas/genética , Claudinas/metabolismo , Evolução Molecular , Animais , Pessoa de Meia-Idade , Prognóstico , Linhagem Celular Tumoral , Camundongos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Idoso , Antineoplásicos Fitogênicos/uso terapêuticoRESUMO
Cuproptosis is a novel discovered mode of programmed cell death. To identify the molecular regulatory patterns related to cuproptosis, this study was designed for exploring the correlation between cuproptosis-related genes (CRGs) and the prognosis, metabolism, and treatment of hepatocellular carcinoma (HCC). Cancer Genome Atlas (TCGA) database was used to screen 363 HCC samples, which were categorized into 2 clusters based on the expression of CRGs. Survival analysis demonstrated that overall survival (OS) was better in Cluster 1 than Cluster 2 which might to be relevant to differences in metabolic based on functional analysis. With LASSO regression analysis and univariate COX regression, 8 prognosis-related genes were screened, a differently expressed genes (DEGs) were then constructed (HCC patients' DEGs)-based signature. The signature's stability was also validated in the 2 independent cohorts and test cohorts (GSE14520, HCC dataset in PCAWG). The 1-year, 3-year, and 5-year area under the curve (AUC) were 0.756, 0.706, and 0.722, respectively. The signature could also well predict the response to chemotherapy, targeted and transcatheter arterial chemoembolization (TACE) by providing a risk score. Moreover, the correlation was uncovered by the research between the metabolism and risk score. In conclusion, a unique cuproptosis-related signature that be capable of predicting patients' prognosis with HCC, and offered valuable insights into chemotherapy, TACE and targeted therapies for these patients has been developed.
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Drought is a complex and dynamic natural phenomenon. A single drought index can hardly reflect the multi-type characteristics of drought, and comprehensive drought indices that incorporate data from multiple sources have been proposed recently. In this study, an Optimized Comprehensive Drought Index (OCDI) was constructed by taking into account the lag time of meteorological drought, agricultural drought and hydrological drought. The Standardized Precipitation Evapotranspiration Index (SPEI), Vegetation Condition Index (VCI), and Water Storage Deficit Index (WSDI) represented the three types of droughts, respectively. Specifically, we used the Solar-induced Chlorophyll Fluorescence (SIF) to characterize the vegetation condition instead of the Normalized Difference Vegetation Index (NDVI). The application results of the proposed drought index in the middle reaches of Yellow River basin (MRYRB) showed that the lag time of different types of drought indices had seasonal differences, with a shorter lag time in summer (0-4 months) and a longer lag time in winter and spring (> 4 months). For typical drought events, the drought intensity and duration identified by OCDI were compatible with the drought evolution characteristics and consistent with the historical records, therefore, OCDI is more suitable for drought monitoring in the study area. Based on the monitoring results of the OCDI, the average number of droughts in the MRYRB was 16 times, with a duration of 2.8 months and an average drought intensity of 0.28 (at moderate drought grade). Drought times and intensity were higher in the northwestern part of the study area, and spring was a high-frequency period for drought occurrences.