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Whereas oncogenes can potentially be inhibited with small molecules, the loss of tumour suppressors is more common and is problematic because the tumour-suppressor proteins are no longer present to be targeted. Notable examples include SMARCB1-mutant cancers, which are highly lethal malignancies driven by the inactivation of a subunit of SWI/SNF (also known as BAF) chromatin-remodelling complexes. Here, to generate mechanistic insights into the consequences of SMARCB1 mutation and to identify vulnerabilities, we contributed 14 SMARCB1-mutant cell lines to a near genome-wide CRISPR screen as part of the Cancer Dependency Map Project1-3. We report that the little-studied gene DDB1-CUL4-associated factor 5 (DCAF5) is required for the survival of SMARCB1-mutant cancers. We show that DCAF5 has a quality-control function for SWI/SNF complexes and promotes the degradation of incompletely assembled SWI/SNF complexes in the absence of SMARCB1. After depletion of DCAF5, SMARCB1-deficient SWI/SNF complexes reaccumulate, bind to target loci and restore SWI/SNF-mediated gene expression to levels that are sufficient to reverse the cancer state, including in vivo. Consequently, cancer results not from the loss of SMARCB1 function per se, but rather from DCAF5-mediated degradation of SWI/SNF complexes. These data indicate that therapeutic targeting of ubiquitin-mediated quality-control factors may effectively reverse the malignant state of some cancers driven by disruption of tumour suppressor complexes.
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Complexos Multiproteicos , Mutação , Neoplasias , Proteína SMARCB1 , Animais , Feminino , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Sistemas CRISPR-Cas , Edição de Genes , Neoplasias/genética , Neoplasias/metabolismo , Proteína SMARCB1/deficiência , Proteína SMARCB1/genética , Proteína SMARCB1/metabolismo , Proteínas Supressoras de Tumor/deficiência , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Complexos Multiproteicos/química , Complexos Multiproteicos/metabolismo , Proteólise , Ubiquitina/metabolismoRESUMO
The interaction between menin and histone-lysine N-methyltransferase 2A (KMT2A) is a critical dependency for KMT2A- or nucleophosmin 1 (NPM1)-altered leukemias and an emerging opportunity for therapeutic development. JNJ-75276617 is a novel, orally bioavailable, potent, and selective protein-protein interaction inhibitor of the binding between menin and KMT2A. In KMT2A-rearranged (KMT2A-r) and NPM1-mutant (NPM1c) AML cells, JNJ-75276617 inhibited the association of the menin-KMT2A complex with chromatin at target gene promoters, resulting in reduced expression of several menin-KMT2A target genes, including MEIS1 and FLT3. JNJ-75276617 displayed potent anti-proliferative activity across several AML and ALL cell lines and patient samples harboring KMT2A- or NPM1-alterations in vitro. In xenograft models of AML and ALL, JNJ-75276617 reduced leukemic burden and provided a significant dose-dependent survival benefit accompanied by expression changes of menin-KMT2A target genes. JNJ-75276617 demonstrated synergistic effects with gilteritinib in vitro in AML cells harboring KMT2A-r. JNJ-75276617 further exhibited synergistic effects with venetoclax and azacitidine in AML cells bearing KMT2A-r in vitro, and significantly increased survival in mice. Interestingly, JNJ-75276617 showed potent anti-proliferative activity in cell lines engineered with recently discovered mutations (MEN1M327I or MEN1T349M) that developed in patients refractory to the menin-KMT2A inhibitor revumenib. A co-crystal structure of menin in complex with JNJ-75276617 indicates a unique binding mode distinct from other menin-KMT2A inhibitors, including revumenib. JNJ-75276617 is being clinically investigated for acute leukemias harboring KMT2A or NPM1 alterations, as a monotherapy for relapsed/refractory (R/R) acute leukemia (NCT04811560), or in combination with AML-directed therapies (NCT05453903).
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The domestication process progressively differentiated wild relatives from modern cultivars, thus impacting plant-associated microorganisms. Endophytic bacterial communities play vital roles in plant growth, development, and health, which contribute to the crop's sustainable development. However, how plant domestication impacts endophytic bacterial communities and relevant root exudates in wheat remains unclear. First, we have observed that the domestication process increased the root endophytic microbial community diversity of wheat while decreasing functional diversity. Second, domestication decreased the endophytic bacterial co-occurrence network stability, and it did significantly alter the abundances of core microorganisms or potential probiotics. Third, untargeted LC-MS metabolomics revealed that domestication significantly altered the metabolite profiles, and the abundances of various root exudates released were significantly correlated with keystone taxa including the Chryseobacterium, Massilia, and Lechevalieria. Moreover, we found that root exudates, especially L-tyrosine promote the growth of plant-beneficial bacteria, such as Chryseobacterium. Additionally, with L-tyrosine and Chryseobacterium colonized in the roots, the growth of wild wheat's roots was significantly promoted, while no notable effect could be found in the domesticated cultivars. Overall, this study suggested that wild wheat as a key germplasm material, and its native endophytic microbes may serve as a resource for engineering crop microbiomes to improve the morphological and physiological traits of crops in widely distributed poor soils.
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This study aimed to assess the prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) in patients with relapsed multiple myeloma (MM). Fifty-one consecutive patients with relapsed MM were enrolled in this retrospective study. 18F-FDG parameters based on the Italian Myeloma Criteria for PET Use (IMPeTUs) and clinical data were analyzed for overall survival (OS) and progression-free survival (PFS). The Cox proportional risk model was used for univariate and multivariate analysis, and Kaplan-Meier survival curves were used for survival analysis. The median length of follow-up was 20 months (IQR, 5-29 months), the median PFS for the entire cohort was 8 months (IQR, 3-17 months) and the median OS was 21 months (IQR, 8-49 months). Multivariate survival analysis demonstrated that the Deauville score of BM > 3 [HR 2.900, 95% CI (1.011, 8.319), P = 0.048] and the presence of EMD [HR 3.134, 95% CI (1.245, 7.891), P = 0.015] were independent predictors of poor PFS. The presence of EMD [HR 12.777, 95% CI (1.825, 89.461), P = 0.010] and the reduced platelets count [HR 7.948, 95% CI (1.236, 51.099), P = 0.029] were adversely associated with OS. 18F-FDG PET/CT parameters based on IMPeTUs have prognostic significance in patients with relapsed MM.
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The patterns and biological functions of copper homeostasis-related genes (CHRGs) in acute myeloid leukemia (AML) remain unclear. We explored the patterns and biological functions of CHRGs in AML. Using independent cohorts, including TCGA-GTEx, GSE114868, GSE37642, and clinical samples, we identified 826 common differentially expressed genes. Specifically, 12 cuproptosis-related genes (e.g., ATP7A, ATP7B) were upregulated, while 17 cuproplasia-associated genes (e.g., ATOX1, ATP7A) were downregulated in AML. We used LASSO-Cox, Kaplan-Meier, and Nomogram analyses to establish prognostic risk models, effectively stratifying patients with AML into high- and low-risk groups. Subgroup analysis revealed that high-risk patients exhibited poorer overall survival and involvement in fatty acid metabolism, apoptosis, and glycolysis. Immune infiltration analysis indicated differences in immune cell composition, with notable increases in B cells, cytotoxic T cells, and memory T cells in the low-risk group, and increased monocytes and neutrophils in the high-risk group. Single-cell sequencing analysis corroborated the expression characteristics of critical CHRGs, such as MAPK1 and ATOX1, associated with the function of T, B, and NK cells. Drug sensitivity analysis suggested potential therapeutic agents targeting copper homeostasis, including Bicalutamide and Sorafenib. PCR validation confirmed the differential expression of 4 cuproptosis-related genes (LIPT1, SLC31A1, GCSH, and PDHA1) and 9 cuproplasia-associated genes (ATOX1, CCS, CP, MAPK1, SOD1, COA6, PDK1, DBH, and PDE3B) in AML cell line. Importantly, these genes serve as potential biomarkers for patient stratification and treatment. In conclusion, we shed light on the expression patterns and biological functions of CHRGs in AML. The developed risk models provided prognostic implications for patient survival, offering valuable information on the regulatory characteristics of CHRGs and potential avenues for personalized treatment in AML.
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Cobre , Homeostase , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/diagnóstico , Cobre/metabolismo , Homeostase/genética , Prognóstico , Masculino , Feminino , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
BACKGROUND & AIMS: Nonampullary duodenal neuroendocrine tumors (NAD-NETs) are rare with limited evidence regarding endoscopic treatment. The study aimed to investigate the efficacy and safety of endoscopic resection of well-differentiated NAD-NETs and evaluate long-term outcomes, including local recurrence and metastasis. METHODS: A total of 78 patients with NAD-NETs who underwent endoscopic resection between January 2011 and August 2022 were included. The clinicopathologic characteristics and treatment outcomes were collected and analyzed. RESULTS: En bloc resection was achieved for 74 of the tumors (94.9%) and R0 resection was obtained in 68 of the tumors (87.2%). Univariate analysis identified tumors in the second part of the duodenum, tumor size ≥ 10 mm and muscularis propria invasion as risk factors for non-curative resection. Two patients with R1 resection (vertical margin involvement) and two patients with lymphovascular invasion underwent additional surgery. Four patients experienced adverse events (5.1%), including two cases of delayed bleeding and two cases of perforation, all successfully managed conservatively. During a median follow-up period of 62.6 months, recurrence and lymph node metastasis were only detected in one patient with R1 resection 3 months after the original procedure. CONCLUSION: Endoscopic resection is safe and effective and provides a favorable long-term outcome for patients with well-differentiated NAD-NETs without regional lymph node or distant metastasis.
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Rubber-derived chemicals (RDCs) originating from tire and road wear particles are transported into road stormwater runoff, potentially threatening organisms in receiving watersheds. However, there is a lack of knowledge on time variation of novel RDCs in runoff, limiting initial rainwater treatment and subsequent rainwater resource utilization. In this study, we investigated the levels and time-concentration profiles of 35 target RDCs in road stormwater runoff from eight functional areas in the Greater Bay Area, South China. The results showed that the total concentrations of RDCs were the highest on the expressway compared with other seven functional areas. N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, benzothiazole, and 1,3-diphenylguanidine were the top four highlighted RDCs (ND-228840 ng/L). Seasonal and spatial differences revealed higher RDC concentrations in the dry season as well as in less-developed regions. A lag effect of reaching RDC peak concentrations in road stormwater runoff was revealed, with a lag time of 10-90 min on expressways. Small-intensity rainfall triggers greater contamination of rubber-derived chemicals in road stormwater runoff. Environmental risk assessment indicated that 35% of the RDCs posed a high risk, especially PPD-quinones (risk quotient up to 2663). Our findings contribute to a better understanding of managing road stormwater runoff for RDC pollution.
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Chuva , Borracha , Cidades , Poluentes Químicos da Água/análise , Monitoramento Ambiental , ChinaRESUMO
A gram-stain-negative, aerobic, rod-shaped bacterium strain CJK-A8-3T was isolated from a polyamine-enriched seawater sample collected from the Changjiang River estuary of China. The colonies were white and circular. Strain CJK-A8-3T grew optimally at 35 °C, pH 7.0 and 1.5% NaCl. Its polar lipids contained phosphatidylglycerol, phosphatidic acid, unidentified glycolipids, and a combination of phospholipids and glycolipids. The respiratory quinone was ubiquinone-10, and its main fatty acids were C16:0, 11-methyl C18:1ω7c and Summed Feature 8 (including C18:1ω7c/C18:1ω6c). The phylogenetic tree based on 16S rRNA genes placed strain CJK-A8-3T in a new linage within the genus Devosia. 16S rRNA gene sequence of strain CJK-A8-3T showed identities of 98.50% with Devosia beringensis S02T, 98.15% with D. oryziradicis, and 98.01% with D. submarina JCM 18935T. The genome size of strain CJK-A8-3T was 3.81 Mb with the DNA G + C content 63.9%, higher than those of the reference strains (60.4-63.8%). The genome contained genes functional in the metabolism of terrigenous aromatic compounds, alkylphosphonate and organic nitrogen, potentially beneficial for nutrient acquirement and environmental remediation. It also harbored genes functional in antibiotics resistance and balance of osmotic pressure, enhancing their adaptation to estuarine environments. Both genomic investigation and experimental verification showed that strain CJK-A8-3T could be versatile and efficient to use diverse organic nitrogen compounds as carbon and nitrogen sources. Based on phenotypic, chemotaxonomic, phylogenetic and genomic characteristics, strain CJK-A8-3T was identified as a novel Devosia species, named as Devosia aquimaris sp. nov. The type strain is CJK-A8-3T (= MCCC 1K06953T = KCTC 92162T).
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Estuários , Hyphomicrobiaceae , Filogenia , RNA Ribossômico 16S/genética , Rios , DNA Bacteriano/genética , Análise de Sequência de DNA , Hibridização de Ácido Nucleico , Técnicas de Tipagem Bacteriana , Água do Mar/microbiologia , Ácidos Graxos/análise , Fosfolipídeos/análise , Glicolipídeos , China , NitrogênioRESUMO
Obstructive sleep apnea (OSA) is a common respiratory disorder. Multiple organs, especially the central nervous system (CNS), are damaged, and dysfunctional when intermittent hypoxia (IH) occurs during sleep for a long time. The quality of life of individuals with OSA is significantly impacted by cognitive decline, which also escalates the financial strain on their families. Consequently, the development of novel therapies becomes imperative. IH induces oxidative stress, endoplasmic reticulum stress, iron deposition, and neuroinflammation in neurons. Synaptic dysfunction, reactive gliosis, apoptosis, neuroinflammation, and inhibition of neurogenesis can lead to learning and long-term memory impairment. In addition to nerve injury, the role of IH in neuroprotection was also explored. While causing neuron damage, IH activates the neuronal self-repairing mechanism by regulating antioxidant capacity and preventing toxic protein deposition. By stimulating the proliferation and differentiation of neural stem cells (NSCs), IH has the potential to enhance the ratio of neonatal neurons and counteract the decline in neuron numbers. This review emphasizes the perspectives and opportunities for the neuroprotective effects of IH and informs novel insights and therapeutic strategies in OSA.
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Hipóxia , Neurônios , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Neurônios/fisiologia , Hipóxia/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Cognição/fisiologia , Estresse Oxidativo/fisiologia , AnimaisRESUMO
Low-density polyethylene (LDPE) conduces massive environmental accumulation due to its high production and recalcitrance to environment. In this study, We successfully enriched and isolated two strains, Nitratireductor sp. Z-1 and Gordonia sp. Z-2, from coastal plastic debris capable of degrading LDPE film. After a 30-day incubation at 30 â, strains Z-1 and Z-2 decreased the weight of branched-LDPE (BLDPE) film by 2.59â¯% and 10.27â¯% respectively. Furthermore, high temperature gel permeation chromatography (HT-GPC) analysis revealed molecular weight reductions of 7.69â¯% (Z-1) and 23.22â¯% (Z-2) in the BLDPE film. Scanning electron microscope (SEM) image showed the presence of microbial colonization and perforations on the film's surface. Fourier transform infrared spectroscopy (FTIR) analysis indicated novel functional groups, such as carbonyl and carbon-carbon double bonds in LDPE films. During LDPE degradation, both strains produced extracellular reactive oxygen species (ROS). GC-MS analysis revealed the degradation products included short-chain alkanes, alkanols, fatty acids, and esters. Genomic analysis identified numerous extracellular enzymes potentially involved in LDPE chain scission. A model was proposed suggesting a coordinated role between ROS and extracellular enzymes in the biodegradation of LDPE. This indicates strains Z-1 and Z-2 can degrade LDPE, providing a basis for deeper exploration of biodegradation mechanisms.
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Biodegradação Ambiental , Plásticos , Polietileno , Praias , Espectroscopia de Infravermelho com Transformada de Fourier , Espécies Reativas de Oxigênio/metabolismo , Microscopia Eletrônica de VarreduraRESUMO
The presence of polycyclic aromatic hydrocarbons (PAHs) pollution on urban road surfaces is one of the major environmental concerns. However, knowledge on the distribution variability of PAHs in road dusts (RDS) and stormwater is limited, which would restrict the further risk evaluation and mitigation implementation of PAHs in road stormwater runoff. This study collected RDS samples and stormwater samples on fourteen urban roads in Shenzhen, China. This study investigated the variation of sixteen PAHs species in RDS and stormwater, and further evaluated the intrinsic and extrinsic factors which influence PAHs accumulation on urban road surfaces. The research outcomes showed significant differences on spatial distribution of PAHs in RDS and in stormwater. The land use types, industrial, commercial and port areas and vehicular volume have a positive relationship with PAHs abundance while dust particle size showed a negative correlation with PAHs abundance. For two phases in stormwater, fluctuation of PAHs with the rainfall duration in total dissolved solid (TDS) was more intensive than in dissolved liquid phase (DLP). This indicated when PAHs attached to RDS enter stormwater, most of PAHs still tend to be on solid particles than in liquid. The study outcomes are expected to contribute to efficient designs of PAHs polluted stormwater mitigation.
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Poeira , Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos , Chuva , Poluentes Químicos da Água , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , Chuva/química , China , Poeira/análise , CidadesRESUMO
This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 µmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 µmol·L~(-1)), low-concentration(10 µmol·L~(-1)) saikosaponin D, and high-concentration(16 µmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3â ¡/LC3â and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.
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Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Caspase 3 , Proteína X Associada a bcl-2 , Proteína Beclina-1/farmacologia , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/genética , Apoptose , Neoplasias Pancreáticas/tratamento farmacológico , Caspases , AutofagiaRESUMO
Previously studies have reported that MAGs (Metagenome-assembled genomes) belong to "Candidatus Manganitrophaceae" of phylum Nitrospirota with chemolithoautotrophic manganese oxidation potential exist in freshwater and hydrothermal environments. However, Nitrospirota members with chemolithoautotrophic manganese oxidation potential have not been reported in other marine environments. Through metagenomic sequencing, assembly and binning, nine metagenome-assembled genomes belonging to Nitrospirota are recovered from sediment of different depths in the polymetallic nodule area. Through the key functional genes annotation results, we find that these Nitrospirota have limited potential to oxidize organic carbon because of incomplete tricarboxylic acid cycle and most of them (6/9) have carbon dioxide fixation potential through different pathway (rTCA, WL or CBB). One MAG belongs to order Nitrospirales has the potential to use manganese oxidation to obtain energy for carbon fixation. In addition to manganese ions, the oxidation of inorganic nitrogen, sulfur, hydrogen and carbon monoxide may also provide energy for the growth of these Nitrospirota. In addition, different metal ion transport systems can help those Nitrospirota to resist heavy metal in sediment. Our work expands the understanding of the metabolic potential of Nitrospirota in sediment of polymetallic nodule region and may contributes to promoting the study of chemolithoautotrophic manganese oxidation.
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Genoma Bacteriano , Sedimentos Geológicos , Metagenoma , Sedimentos Geológicos/microbiologia , Oceano Pacífico , Manganês/metabolismo , Bactérias/genética , Bactérias/classificaçãoRESUMO
Acute type A aortic dissection may originate from a primary intimal tear located in the ascending aorta and often extends retrogradely into the aortic root. How to prevent bleeding in the aortic root and eliminate false lumen is very important in aortic dissection. We have developed a modified anastomotic technique that involves inverting adventitial and graft into aorta and reinforcing with a felt strip on the external border of the aortic wall. Since 2020, 45 consecutive patients with type A aortic coarctation have undergone this aortic root reconstruction procedure, to date, none have been reopened for bleeding or remnant dissection.
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Aneurisma da Aorta Torácica , Dissecção Aórtica , Humanos , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aorta/cirurgia , Aneurisma da Aorta Torácica/cirurgiaRESUMO
Depression is a common occurrence among cancer patients, and it significantly impacts their clinical outcomes and quality of life, with a high incidence during anti-tumor treatment or after surgery. The association between surgery and depression is the result of the interaction of various factors, including physiological, psychological, and social factors, all of which are intertwined and make patients susceptible to depression after surgical treatment. Postoperative depression has a significant negative impact on many aspects of cancer patients, and it requires timely identification and intervention to improve the overall outcome.
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BACKGROUND: The severity and frequency of drought are expected to increase substantially in the coming century and dramatically reduce crop yields. Manipulation of rhizosphere microbiomes is an emerging strategy for mitigating drought stress in agroecosystems. However, little is known about the mechanisms underlying how drought-resistant plant recruitment of specific rhizosphere fungi enhances drought adaptation of drought-sensitive wheats. Here, we investigated microbial community assembly features and functional profiles of rhizosphere microbiomes related to drought-resistant and drought-sensitive wheats by amplicon and shotgun metagenome sequencing techniques. We then established evident linkages between root morphology traits and putative keystone taxa based on microbial inoculation experiments. Furthermore, root RNA sequencing and RT-qPCR were employed to explore the mechanisms how rhizosphere microbes modify plant response traits to drought stresses. RESULTS: Our results indicated that host plant signature, plant niche compartment, and planting site jointly contribute to the variation of soil microbiome assembly and functional adaptation, with a relatively greater effect of host plant signature observed for the rhizosphere fungi community. Importantly, drought-resistant wheat (Yunhan 618) possessed more diverse bacterial and fungal taxa than that of the drought-sensitive wheat (Chinese Spring), particularly for specific fungal species. In terms of microbial interkingdom association networks, the drought-resistant variety possessed more complex microbial networks. Metagenomics analyses further suggested that the enriched rhizosphere microbiomes belonging to the drought-resistant cultivar had a higher investment in energy metabolism, particularly in carbon cycling, that shaped their distinctive drought tolerance via the mediation of drought-induced feedback functional pathways. Furthermore, we observed that host plant signature drives the differentiation in the ecological role of the cultivable fungal species Mortierella alpine (M. alpina) and Epicoccum nigrum (E. nigrum). The successful colonization of M. alpina on the root surface enhanced the resistance of wheats in response to drought stresses via activation of drought-responsive genes (e.g., CIPK9 and PP2C30). Notably, we found that lateral roots and root hairs were significantly suppressed by co-colonization of a drought-enriched fungus (M. alpina) and a drought-depleted fungus (E. nigrum). CONCLUSIONS: Collectively, our findings revealed host genotypes profoundly influence rhizosphere microbiome assembly and functional adaptation, as well as it provides evidence that drought-resistant plant recruitment of specific rhizosphere fungi enhances drought tolerance of drought-sensitive wheats. These findings significantly underpin our understanding of the complex feedbacks between plants and microbes during drought, and lay a foundation for steering "beneficial keystone biome" to develop more resilient and productive crops under climate change. Video Abstract.
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Ascomicetos , Resistência à Seca , Triticum , Rizosfera , Genótipo , Fungos/genéticaRESUMO
Background and Purpose: The role of serum uric acid (UA) level in patients suffering from stroke remains controversial. Our aim was to investigate the effect of UA level on clinical outcomes in patients with intracerebral hemorrhage (ICH). Methods: In the retrospective cohort study, we analyzed data from 250 patients with intracerebral hemorrhage (85 women and 165 men) to investigate the difference in UA levels between patients with a good prognosis and those with a poor prognosis. Additionally, we analyzed the impact of UA levels on the risk of short-time prognosis of ICH patients. Results: Patients with a good prognosis presented with significantly lower levels of UA (348.71 ± 84.97 µmol/L) than those with poor prognosis (393.06 ± 148.46 µmol/L). Furthermore, multivariate logistic regression model demonstrated that a high UA level was a likely risk factor for worse prognosis among patients suffering in ICH (odds ratio [95% confidence interval], 1.006 [1.0012, 1.0108]; P = 0.015). Additionally, UA has a threshold effect value of 363.9 µmol/L and was presented in levels that were in a nonlinear relationship with incidence rate of short-time prognosis outcome of ICH patients. Conclusion: Our findings indicate that higher UA levels can increase the risk of poor clinical prognosis in patients with ICH and high UA levels are not conductive to the clinical prognosis of patients with ICH. These findings provide a new perspective on the treatment and prevention of ICH.
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Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), a type of fatty acid that has many health benefits, are of increasing concern. Herein, we developed a method for the rapid esterification and enrichment of ω-3 PUFAs in eggs, which includes microwave-assisted esterification (MAE) and electrically enhanced solid-phase microextraction (EE-SPME). Combined with gas chromatographic, efficient detection of ω-3 PUFAs was achieved in eggs. Under microwave radiation, the esterification efficiency exhibited a significant increase ranging from 5.06 to 10.65 times. The EE-SPME method reduced extraction time from 50 to 15 min. In addition, improvements in extractive fiber coating materials were explored, which ensured efficient extraction of ω-3 PUFAs. Under the optimal conditions, the method displayed a low detection limit (1.01-1.54 µg L-1), good recoveries (85.82%-106.01%), and wide linear range (7.5-1000 µg L-1), which was successfully applied to determine ω-3 PUFAs in real egg samples.