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BACKGROUND: Liver surgery during the perioperative period often leads to a significant complication known as hepatic ischemia-reperfusion (I/R) injury. Hepatic I/R injury is linked to the innate immune response. The cGAS-STING pathway triggers the activation of innate immune through the detection of DNA within cells. Nevertheless, the precise mechanism and significance of the cGAS-STING pathway in hepatic I/R injury are yet to be investigated. METHODS: Mouse model of hepatic I/R injury was used in the C57BL/6 WT mice and the STING knockout (STING-KO) mice. In addition, purified primary hepatocytes were used to construct oxygen-glucose deprivation reperfusion (OGD-Rep) treatment models. RESULTS: Our research revealed a notable increase in mRNA and protein levels of cGAS and STING in liver during I/R injury. Interestingly, the lack of STING exhibited a safeguarding impact on hepatic I/R injury by suppressing the elevation of liver enzymes, liver cell death, and inflammation. Furthermore, pharmacological cGAS and STING inhibition recapitulated these phenomena. Macrophages play a crucial role in the activation of the cGAS-STING pathway during hepatic I/R injury. The cGAS-STING pathway experiences a significant decrease in activity and hepatic I/R injury is greatly diminished following the elimination of macrophages. Significantly, we demonstrate that the activation of the cGAS-STING pathway is primarily caused by the liberation of mitochondrial DNA (mtDNA) rather than nuclear DNA (nDNA). Moreover, the safeguarding of the liver against I/R injury is also attributed to the hindrance of mtDNA release through the utilization of inhibitors targeting mPTP and VDAC oligomerization. CONCLUSIONS: The results of our study suggest that the release of mtDNA plays a significant role in causing damage to liver by activating the cGAS-STING pathway during I/R injury. Furthermore, inhibiting the release of mtDNA can provide effective protection against hepatic I/R injury.
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DNA Mitocondrial , Fígado , Proteínas de Membrana , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nucleotidiltransferases , Traumatismo por Reperfusão , Transdução de Sinais , Animais , DNA Mitocondrial/metabolismo , DNA Mitocondrial/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Nucleotidiltransferases/metabolismo , Proteínas de Membrana/metabolismo , Fígado/metabolismo , Fígado/patologia , Fígado/irrigação sanguínea , Masculino , Hepatócitos/metabolismo , Camundongos , Macrófagos/metabolismoRESUMO
OBJECTIVES AND DESIGN: As an interferon-inducible protein, Viperin has broad-spectrum antiviral effects and regulation of host immune responses. We aim to investigate how Viperin regulates interferon-γ (IFN-γ) production in macrophages to control Mycobacterium tuberculosis (Mtb) infection. METHODS: We use Viperin deficient bone-marrow-derived macrophage (BMDM) to investigate the effects and machines of Viperin on Mtb infection. RESULTS: Viperin inhibited IFN-γ production in macrophages and in the lung of mice to promote Mtb survival. Further insight into the mechanisms of Viperin-mediated regulation of IFN-γ production revealed the role of TANK-binding kinase 1 (TBK1), the TAK1-dependent inhibition of NF-kappa B kinase-epsilon (IKKε), and interferon regulatory factor 3 (IRF3). Inhibition of the TBK1-IKKε-IRF3 axis restored IFN-γ production reduced by Viperin knockout in BMDM and suppressed intracellular Mtb survival. Moreover, Viperin deficiency activated the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, which promoted IFN-γ production and inhibited Mtb infection in BMDM. Additionally, a combination of the anti-TB drug INH treatment in the absence of Viperin resulted in further IFN-γ production and anti-TB effect. CONCLUSIONS: This study highlights the involvement of TBK1-IKKε-IRF3 axis and JAK-STAT signaling pathways in Viperin-suppressed IFN-γ production in Mtb infected macrophages, and identifies a novel mechanism of Viperin on negatively regulating host immune response to Mtb infection.
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Fator Regulador 3 de Interferon , Interferon gama , Macrófagos , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis , Proteínas Serina-Treonina Quinases , Proteínas , Transdução de Sinais , Animais , Interferon gama/metabolismo , Interferon gama/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Mycobacterium tuberculosis/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Fator Regulador 3 de Interferon/metabolismo , Camundongos , Proteínas/genética , Proteínas/metabolismo , Quinase I-kappa B/metabolismo , Janus Quinases/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Camundongos Knockout , Tuberculose/imunologia , Pulmão/imunologia , Pulmão/microbiologia , Proteína ViperinaRESUMO
OBJECTIVES AND DESIGN: Dendritic cells (DCs) are one of the key immune cells in bridging innate and adaptive immune response against Mycobacterium tuberculosis (Mtb) infection. Interferons (IFNs) play important roles in regulating DC activation and function. Virus-inhibitory protein, endoplasmic reticulum-associated, interferon-inducible (Viperin) is one of the important IFN-stimulated genes (ISGs), and elicits host defense against infection. METHODS: We investigated the effects and mechanisms of Viperin on DC activation and function using Viperin deficient bone marrow-derived dendritic cells (BMDCs) during Mtb infection. RESULTS: Viperin deficiency enhanced phagocytic activity and increased clearance of Mtb in DCs, produced higher abundance of NO, cytokine including interleukin-12 (IL-12), Tumor necrosis factor-α (TNF-α), IL-1ß, IL-6 and chemokine including CXCL1, CXCL2 and CXCL10, elevated MHC I, MHC II and co-stimulatory molecules expression, and enhanced CD4+ and CD8+ T cell responses. Mechanistically, Viperin deficiency promoted DC activation and function through NF-κB p65 activation. NF-κB p65 inhibitor prevented cytokine and chemokine production, and co-stimulatory molecules expression promoted by Viperin deficiency. CONCLUSIONS: These results suggest that Mtb induced Viperin expression could impair the activation of host defense function of DCs and DC-T cell cross talk during Mtb infection. This research may provide a potential target for future HDT in TB therapy.
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Mycobacterium tuberculosis , Tuberculose , Proteína Viperina , Quimiocinas/metabolismo , Citocinas , Células Dendríticas , Mycobacterium tuberculosis/metabolismo , NF-kappa B/metabolismo , Proteína Viperina/metabolismo , AnimaisRESUMO
Manipulation of polarization states in a complex structured optical field during propagation has become an important topic due to its fundamental interest and potential applications. This work demonstrates the effect of the caustic and twisting phases on the polarization states of a vector beam experimentally and theoretically. The novel properties of polarization evolution, especially the conversions of different states of polarization (SoPs) in a twisted caustic vector beam, occur during propagation in free space because of the modulation of twisting and caustic phases. The orthogonal polarization components tend to appear on the beam centers of two foci, and the two focal distances are closely related to the caustic and twisting phases. The twisting and caustic phases can manipulate the conversions between linear and circular polarization components that occur during propagation. These results provide a new approach to more complex manipulations of a structured optical field, especially in tailoring the evolution of polarization states and two foci. They may find potential applications in the corresponding field.
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Type I interferon pathway is a crucial component of innate immune signaling upon pathogen infection or endogenous instability. An imbalance of type I interferon can lead to many diseases, such as autoimmune diseases and inflammatory diseases. Meanwhile, the side effects of clinical drugs on type I interferon signaling may result in impaired outcomes in clinical treatment, especially in cancer immunotherapy which is associated with type I interferon signaling. Here, we found that sorafenib, an FDA-approved drug for HCC chemotherapy, suppresses both DNA- and RNA-sensing mediated type I interferon pathway. Mechanistically, sorafenib treatment induces the autophagic degradation of MAVS, cGAS, TBK1, and IRF3, and attenuates the signaling transduction. In addition, sorafenib also inhibits the recruiting of STING or MAVS with TBK1 and IRF3. This work reveals the negative role of sorafenib in the regulation of type I interferon pathway. Sorafenib treatment is not only a potential drug for autoimmune disease and inflammation diseases, but also needs to be noticed in HCC chemotherapy.
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Carcinoma Hepatocelular , Interferon Tipo I , Neoplasias Hepáticas , Humanos , Imunidade Inata , Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/metabolismo , Nucleotidiltransferases/metabolismo , Proteínas Serina-Treonina Quinases , Sorafenibe/farmacologiaRESUMO
As an important effector in response to various intracellular or extracellular stimuli, the NF-κB family extensively participates in a wide spectrum of biological events, and its dysregulation may result in many pathological conditions, such as microbial infection, tumor progression, and neurodegenerative disorders. Previous investigations showed that multiple types of ubiquitination play critical roles in the modulation of the NF-κB signaling pathway, yet the molecular mechanisms are still poorly understood. In the current study, we identified TRIM25, an E3 ubiquitin ligase, as a novel positive regulator in mediating NF-κB activation in human embryonic kidney 293T (HEK293T), HeLa cells, THP-1 cells, and PBMCs. The expression of TRIM25 promoted TNF-α-induced NF-κB signaling, whereas the knockdown had the opposite effect. Furthermore, TRIM25 interacted with TRAF2 and enhanced the K63-linked polyubiquitin chains attached to TRAF2. Moreover, TRIM25 bridged the interaction of TRAF2 and TAK1 or IKKß. To our knowledge, our study has identified a previously unrecognized role for TRIM25 in the regulation of NF-κB activation by enhancing the K63-linked ubiquitination of TRAF2.
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Quinase I-kappa B/metabolismo , NF-kappa B/metabolismo , Fator 2 Associado a Receptor de TNF/metabolismo , Fatores de Transcrição/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Técnicas de Silenciamento de Genes , Células HEK293 , Células HeLa , Humanos , Leucócitos Mononucleares , Lisina/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/imunologia , Cultura Primária de Células , Células THP-1 , Fatores de Transcrição/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinação/genética , Ubiquitinação/imunologiaRESUMO
Endoclita signifer larvae show olfactory recognition towards volatiles of eucalyptus trunks and humus soils. Further, EsigGOBP1 was identified through larval head transcriptome and speculated as the main odorant-binding proteins in E. signifer larvae. In this study, the highest expression of EsigGOBP1 was only expressed in the heads of 3rd instar larvae of E. signifer, compared with the thorax and abdomen; this was consistent with the phenomenon of habitat transfer of 3rd instar larvae, indicating that EsigGOBP1 was a key OBP gene in E. signifer larvae. Results of fluorescence competition binding assays (FCBA) showed that EsigGOBP1 had high binding affinities to eight GC-EAD active ligands. Furthermore, screening of key active odorants for EsigGOBP1 and molecular docking analysis, indicated that EsigGOBP1 showed high binding activity to alpha-phellandrene in 3rd instar larvae of E. signifer. Conformational analysis of the EsigGOBP1-alpha-phellandrene complex, showed that MET49 and GLU38 were the key sites involved in binding. These results demonstrated that EsigGOBP1 is a key odorant-binding protein in E. signifer larvae, which recognizes and transports eight key volatiles from eucalyptus trunk, especially the main eucalyptus trunks volatile, alpha-phellandrene. Taken together, our results showed that EsigGOBP1 is involved in host selection of E. signifer larvae, which would aid in developing EsigGOBP1 as molecular targets for controlling pests at the larval stage.
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Lepidópteros , Receptores Odorantes , Animais , Monoterpenos Cicloexânicos , Proteínas de Insetos/genética , Larva/metabolismo , Lepidópteros/metabolismo , Simulação de Acoplamento Molecular , Ligação Proteica , Receptores Odorantes/metabolismoRESUMO
BACKGROUND: The application of splenic hilar lymph node (no. 10 LN) dissection (no. 10 LND) for proximal gastric cancer (PGC) remains controversial. This study aimed to investigate the clinical relevance of no. 10 LND from the perspective of long-term survival. METHODS: The main study population included 995 previously untreated patients who underwent laparoscopic radical total gastrectomy between January 2008 and December 2014. Of these 995 patients, 564 underwent no. 10 LND (no. 10D+ group) and the remaining 431 patients did not (no. 10D- group). Propensity score-matching was applied to reduce the effects of confounding factors. The study end points were overall survival (OS) and disease-free survival (DFS). Additionally, 39 patients who received neoadjuvant chemotherapy during the same period also were included as a separate population for analysis. RESULTS: The metastasis rate for no. 10 LN was 10.5 % (59/564). No significant differences were observed in intra- and postoperative complications nor in mortality between the no. 10D+ and no. 10D- groups (all P > 0.05). After 1:1 matching, the two groups were comparable in clinicopathologic characteristics. The no. 10D+ group had significantly better survival than the no. 10D- group (5-year OS: 63.3 % vs 52.2 %, P = 0.003; 5-year DFS: 60.4 % vs 48.1 %, P = 0.013). For the patients who received neoadjuvant chemotherapy, the 5-year OS rates in the no. 10D+ and no. 10D- groups were respectively 50.6 % and 31.3 % (P = 0.150) and the 5-year DFS rates were respectively 51.5 % and 31.3 % (P = 0.123). CONCLUSIONS: Patients with untreated PGC may achieve the benefit of long-term survival from no. 10 LND. For patients with PGC who undergo neoadjuvant chemotherapy, no. 10 LND may not bring survival benefits. However, further validation with a large-sample study is needed.
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Neoplasias Gástricas , Estudos de Casos e Controles , Dissecação , Gastrectomia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Estadiamento de Neoplasias , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
Channel catfish (Ictalurus punctatus) is the primary culture species in the US along with its hybrid made with male blue catfish, I. furcatus. In an effort to improve the nutritional value of channel catfish, the masou salmon Δ5-desaturase like gene (D5D) driven by the common carp beta-actin promoter (ßactin) was inserted into channel catfish. The objectives of this study were to determine the effectiveness of ßactin-D5D for improving n-3 fatty acid production in F1 transgenic channel catfish, as well as examine pleiotropic effects on growth, proximate analysis, disease resistance, and other performance traits. Transgenic F1 channel catfish showed a 33% increase in the relative proportion of n-3 fatty acids coupled with a 15% decrease in n-6 fatty acids and a 17% decrease in n-9 fatty acids when compared to non-transgenic full-siblings (P < 0.01, P < 0.01, P < 0.01). However, while the relative proportion of n-3 fatty acids was achieved, the total amount of fatty acids in the transgenic fish decreased resulting in a reduction of all fatty acids. Insertion of the ßactin-D5D transgene into channel catfish also had large effects on the body composition, and growth of channel catfish. Transgenic channel catfish grew faster, were more disease resistant, had higher protein and moisture percentage, but lower fat percentage than full-sib controls. There were sex effects as performance changes were more dramatic and significant in males. The ßactin-D5D transgenic channel catfish were also more uniform in their fatty acid composition, growth and other traits.
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Animais Geneticamente Modificados/crescimento & desenvolvimento , Dessaturase de Ácido Graxo Delta-5/metabolismo , Ácidos Graxos/metabolismo , Proteínas de Peixes/metabolismo , Flavobacterium/fisiologia , Ictaluridae/crescimento & desenvolvimento , Transgenes , Animais , Animais Geneticamente Modificados/imunologia , Animais Geneticamente Modificados/metabolismo , Animais Geneticamente Modificados/microbiologia , Dessaturase de Ácido Graxo Delta-5/genética , Proteínas de Peixes/genética , Ictaluridae/imunologia , Ictaluridae/metabolismo , Ictaluridae/microbiologiaRESUMO
PURPOSE: To investigate the effect of dynamic changes in systemic inflammatory markers (SIM) on long-term prognosis of patients with gastric cancer (GC). METHODS: A retrospective analysis was performed on the data of 2180 patients with GC who underwent radical gastrectomy in the Fujian medical university Union Hospital from January 2009 to December 2014. Changes in SIM between preoperatively and 1-6 months and 12 months postoperatively were reported. RESULTS: In multivariate analysis, higher preoperative systemic inflammation score (pre-SIS) was independent predictor of poor prognosis (p < 0.05). The optimal time of remeasurement was 12 months postoperatively, based on a longitudinal profile of SIS and accuracy in predicting 5-year overall survival (OS) (area under the curve: 0.712 [95% confidence interval: 0.630-0.785]). According to the association between the conversion of SIS and OS, we classified patients into three risk groups. Kaplan-Meier curves showed significant differences in OS among risk groups. Further Cox multivariate regression analysis showed that only risk groups of SIS and pTNM stage were independent prognostic factors for OS. CONCLUSION: The efficacy of SIS in predicting prognosis 12 months after surgery is superior, and the elevation of SIS 12 months after surgery predicts poor prognosis.
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Mediadores da Inflamação/metabolismo , Neoplasias Gástricas/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Estudos Longitudinais , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Análise Multivariada , Estadiamento de Neoplasias , Neutrófilos/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
INTRODUCTION: To assess the ability of the Age-Adjusted Charlson Comorbidity Index (ACCI) to predict survival after radical gastrectomy in patients with gastric cancer (GC). METHOD: Data from patients with GC who underwent radical gastrectomy from January 2008 to December 2012 in Fujian Medical University Union Hospital were retrospectively analyzed. Patients were categorized into either high ACCI group or low ACCI group based on the effect of ACCI on long-term GC prognosis. 1:1 propensity score matching (PSM) was used to reduce confounding bias. To further analyze the impact of ACCI on the long-term prognosis of patients after radical gastrectomy, a nomogram was built based on the Cox proportional hazards regression model. RESULTS: A total of 1476 patients were included in the analysis. After PSM, there was no statistically significant differences in tumor location, tumor size and tumor stage between low ACCI group (429 cases) and high ACCI group (429 cases) (all P > 0.05). Before and after PSM, the incidence of postoperative complications in high ACCI group was significantly higher than that in low ACCI group (P < 0.05). The 5-year overall survival rate (OS) in low ACCI group was significantly higher than that in high ACCI group. Multivariate analysis showed that ACCI was an independent risk factor for OS (P < 0.05). The Harrell's C-statistics (C-index) of TNMA, a prognostic evaluation system combining ACCI and TNM staging system, was significantly higher than that of TNM staging system in both the modeling and validation groups (all P < 0.05). CONCLUSIONS: ACCI was an independent risk factor for the long-term prognosis of GC patients after radical gastrectomy that could effectively improve the predictive efficacy of the TNM staging system for GC.
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Gastrectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Gastrectomia/efeitos adversos , Humanos , Incidência , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Nomogramas , Complicações Pós-Operatórias/etiologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Ag-Sn-In-Ni-Te alloy ingots were produced through a heating-cooling combined mold continuous casting technique; they were then drawn into wires. However, during the drawing process, the alloy wires tended to harden, making further diameter reduction challenging. To overcome this, heat treatment was necessary to soften the previously drawn wires. The study investigated how variations in heat treatment temperature and holding time affected the microstructure, microhardness and corrosion resistance of the alloy wires. The results indicate that the alloy wires subjected to heat treatment at 700 °C for 2 h not only exhibited a uniform microstructure distribution, but also demonstrated low microhardness and excellent corrosion resistance.
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A series of Ti41Zr25Be34-xNix (x = 4, 6, 8, 10 at.%) and Ti41Zr25Be34-xCux (x = 4, 6, 8 at.%) bulk metallic glasses were investigated to examine the influence of Ni and Cu content on the viscosity, thermoplastic formability, and nanoindentation of Ti-based bulk metallic glasses. The results demonstrate that Ti41Zr25Be30Ni4 and Ti41Zr25Be26Cu8 amorphous alloys have superior thermoplastic formability among the Ti41Zr25Be34-xNix and Ti41Zr25Be34-xCux amorphous alloys due to their low viscosity in the supercooled liquid region and wider supercooled liquid region. The hardness and modulus exhibit obvious variations with increasing Ni and Cu content in Ti-based bulk metallic glasses, which can be attributed to alterations in atomic density. Optimal amounts of Ni and Cu in Ti-based bulk metallic glasses enhance thermoplastic formability and mechanical properties. The influence of Ni and Cu content on the hardness of Ti-based bulk metallic glasses is discussed from the perspective of the mean atomic distance.
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Chrysanthemum indicum Linnén (C. indicum), a medicinal and food herb with various bioactive components, may be of beneficial use in cosmetics and the treatment of skin-related diseases. However, to date, few studies have been reported on its potential preventive and therapeutic effects on skin cancer. Therefore, the present study aimed to investigate the effect and potential mechanism of action of supercritical carbon dioxide extract from C. indicum (CISCFE) on UV-induced skin cancer in a mouse model. Kunming mice were allocated randomly to five treatment groups: Sham, model, low concentration CISCFE, high concentration CISCFE and positive control nicotinamide groups. The dorsal skin of mice was irradiated with UV light for 31 weeks. Histopathological changes, ELISA assays, immunohistochemical analysis and western blotting were performed to investigate the potential therapeutic effects of CISCFE. The results showed that CISCFE alleviated skin oxidative and inflammatory damage in a UV-induced mouse model of skin cancer. Moreover, CISCFE suppressed abnormal activation of proto-oncogene c-Myc and the overexpression of Ki-67 and VEGF, and increased expression of the anti-oncogene PTEN, thereby reducing abnormal proliferation of the epidermis and blood vessels. Additionally, CISCFE increased the protein expression levels of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), Kelch-like ECH associated protein 1 (Keap1) and inhibited the expression of nuclear factor 2 erythroid 2-related factor 2 (Nrf2), phosphorylated (p)-p62 (Ser 349), p-p65 and acetyl-p65 proteins in a UV-induced skin cancer mouse model. In summary, CISCFE exhibited potent anti-skin cancer activity, which may be attributed its potential effects on the p62/Keap1-Nrf2 and SIRT1/NF-κB pathways.
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Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, with the highest single-cause mortality. Monocarboxylate transporter 4 (Mct4) transports intracellular lactate outside, but its role in regulating host immune response against Mtb infection remains unknown. Mct4 expression was upregulated in Mtb-infected macrophages and in patients with TB. Mct4 silencing/deficiency significantly decreased Mtb survival in macrophages and in lungs and spleens of mice, while Mct4 overexpression facilitated Mtb survival in macrophages. Furthermore, Mct4 promoted intracellular lactate transport, nuclear factor κB (NF-κB) p65 activation, and interleukin-10 (IL-10) production upon Mtb infection. Mechanistically, IL-10 silencing and IL-10-neutralizing antibody blocked Mct4 overexpressing increased Mtb survival. Replenishing lactate and NF-κB p65 inhibitor JSH23 treatment could inhibit Mct4 overexpressing increased NF-κB p65 activation, IL-10 production, and Mtb survival in macrophages. This study demonstrates that Mct4 promotes Mtb survival through restricting intracellular lactate accumulation to promote NF-κB p65-mediated IL-10 production and suggests Mct4-NF-κB p65-IL-10 axis a potential target for TB treatment.
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Gamma-aminobutyric acid (GABA) significantly affects plant responses to heavy metals in hydroponics or culture media, but its corresponding effects in plant-soil systems remain unknown. In this study, different GABA dosages (0-8 g kg-1) were added to the rhizosphere of Coreopsis grandiflora grown in Cd-contaminated soils. Cd accumulation in the shoots of C. grandiflora was enhanced by 38.9-159.5% by GABA in a dose-dependent approach because of accelerated Cd absorption and transport. The increase in exchangeable Cd transformed from Fe-Mn oxide and carbonate-bound Cd, which may be mainly driven by decreased soil pH rather than GABA itself, could be a determining factor responsible for this phenomenon. The N, P, and K availability was affected by multiple factors under GABA treatment, which may regulate Cd accommodation and accumulation in C. grandiflora. The rhizospheric environment dynamics remodeled the bacterial community composition, resulting in a decline in overall bacterial diversity and richness. However, several important plant growth-promoting rhizobacteria, especially Pseudomonas and Sphingomonas, were recruited under GABA treatment to assist Cd phytoextraction in C. grandiflora. This study reveals that GABA as a soil amendment remodels the rhizospheric environment (e.g., soil pH and rhizobacteria) to enhance Cd phytoextraction in plant-soil systems.
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Verticillium dahliae is a soilborne plant fungal pathogen that causes Verticillium wilt, a disease that reduces the yields of many economically important crops. Despite its worldwide distribution and harmful impacts, much remains unknown regarding how the numerous effectors of V. dahliae modulate plant immunity. Here, we identified the intracellular effector VdCE11 that induces cell death and defense responses in Nicotiana benthamiana to counter leaf pathogens such as Sclerotinia sclerotiorum and Botrytis cinerea. VdCE11 also contributes to the virulence of V. dahliae in cotton and Arabidopsis. Yeast two-hybrid library screening and immunoprecipitation revealed that VdCE11 interacts physically with the cotton aspartic protease GhAP1. GhAP1 and its Arabidopsis homolog AtAP1 are negative regulators of plant immunity, since disruption of either increased the resistance of cotton or Arabidopsis to V. dahliae. Further, VdCE11 plays a role in promoting the accumulation of the AP1 proteins and increasing its hydrolase activity. Taken together, these results indicate a novel mechanism regulating virulence whereby the secreted effector VdCE11 increases cotton susceptibility to V. dahliae by promoting the accumulation and activity of GhAP1. IMPORTANCE Verticclium dahliae is a plant fungal pathogen that causes a destructive vascular disease on a large number of plant hosts, resulting in great threat to agricultural production. In this study, we identified a V. dahliae effector VdCE11 that induces cell death and defense responses in Nicotiana benthamiana. Meanwhile, VdCE11 contributes to the virulence of V. dahliae in cotton and Arabidopsis. Yeast two-hybrid library screening and immunoprecipitation revealed that VdCE11 interacts physically with the cotton aspartic protease GhAP1. GhAP1 and its Arabidopsis homolog AtAP1 are negative regulators of plant immunity since disruption of either increased the resistance of cotton or Arabidopsis to V. dahliae. Further research showed that VdCE11 plays a role in promoting the accumulation of the AP1 proteins and increasing its hydrolase activity. These results suggested that a novel mechanism regulating virulence whereby VdCE11 increases susceptibility to V. dahliae by promoting the accumulation and activity of GhAP1 in the host.
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Arabidopsis , Humanos , Arabidopsis/microbiologia , Resistência à Doença , Peptídeo Hidrolases , Doenças das Plantas/microbiologia , Saccharomyces cerevisiae , Virulência , GossypiumRESUMO
Copper-coated graphite and copper mixture powders were deposited on AZ31B magnesium alloy and 6061 T6 aluminum alloy substrates under different process parameters by a solid-state cold spray technique. The microstructure of the copper-coated graphite and copper composite coatings was visually examined using photographs taken with an optical microscope and a scanning electron microscope. The surface roughness of the coatings was investigated with a 3D profilometer. The thickness of the coatings was determined through the analysis of the microstructure images, while the adhesion of the coatings was characterized using the scratch test method. The results indicate that the surface roughness of the coatings sprayed on the two different substrates gradually decreases as gas temperature and gas pressure increase. Additionally, the thickness and adhesion of the coatings deposited on the two different substrates both increase with an increase in gas temperature and gas pressure. Comparing the surface roughness, thickness, and adhesion of the coatings deposited on the two different substrates, the surface roughness and adhesion of the coatings on the soft substrate are greater than those of the coatings on the hard substrate, while the thickness of the coatings is not obviously affected by the hardness of the substrate. Furthermore, it is noteworthy that the surface roughness, thickness, and adhesion of the copper-coated graphite and copper composite coatings sprayed on the two different substrates exhibit a distinct linear relationship with particle velocity.
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BACKGROUND: There is no consensus on whether adjuvant chemotherapy (AC) is effective for hepatoid adenocarcinoma of the stomach (HAS). The aim of this study was to investigate the relationship between AC and the long-term prognosis of patients with HAS. METHODS: The clinicopathological data of 239 patients with primary HAS who underwent radical surgery from April 1, 2004 to December 31, 2019 in 14 centers in China were retrospectively analyzed. Patients were divided into the AC group (127 patients) and the nonadjuvant chemotherapy (NAC) group (112 patients). RESULTS: KaplanâMeier (KM) analysis showed that there were no significant differences in the 1-year3-year overall survival rate (OS) and 1-year, 3-year recurrence-free survival rate (RFS) between the AC group and the NAC group (1-year OS: 85.6% vs. 79.8%, 3-year OS: 59.8% vs. 62.4%, 1-year RFS: 69.8% vs. 74.4%, 3-year RFS: 57.2% vs. 55.9%, all P > 0.05). The subpopulation treatment effect pattern plots (STEPP) did not show treatment heterogeneity of AC in patients with HAS. The proportions of local recurrence and metastasis sites in the two groups were similar. Although the smoothed hazard curves of the NAC and AC groups crossed, the peak hazard time was later in the AC group (5.9 and 4.7 months), and the peak hazard rate was lower (0.032 and 0.038, P = 0.987). CONCLUSION: The current AC regimen may not significantly improve the survival of patients with HAS after radical surgery.
Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Quimioterapia Adjuvante , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgiaRESUMO
Screening or breeding exceptional plant species for heavy metal phytoremediation is as important as adopting feasible measures to enhance phytoremediation efficiency, which are largely based on clarifying the mechanisms of heavy metal tolerance and accumulation by plants. In this study, cadmium (Cd) and lead (Pb) tolerance and accumulation characteristics of Rheum officinale, R. palmatum, and R. tanguticum were analysed to assess their phytoremediation potential. The seed germination test indicated that these three rhubarb species could tolerate 10 mg L-1 Cd and 100 mg L-1 Pb. However, when sown in Cd- and Pb-contaminated soil, all three rhubarb species exhibited a relatively high Cd accumulation capacity but a considerably low Pb accumulation capacity according to the bioconcentration factors of Cd (0.42-0.47 in shoots and 0.11-0.15 in roots) and Pb (0.004-0.008 in shoots and 0.007-0.013 in roots). The high Cd translocation factors (3.04-4.24) indicated that these three rhubarb species were suitable for Cd phytoextraction. The changes in rhizospheric physicochemical indices were generally similar among the three rhubarb plants in comparison with those of the unplanted soil. However, differential indicator rhizobacteria were identified for the three rhubarb plants, which may be primarily attributed to their different root system characteristics. These enriched rhizobacteria included many plant growth-promoting bacteria, and several of them were also involved in regulating heavy metal uptake by plants, indicating that three rhubarb species likely recruit differentially beneficial rhizobacteria to maintain plant growth and vitality and to regulate heavy metal uptake in the Cd- and Pb-polluted soil. This study identifies new candidate plant resources for the phytoremediation of Cd-polluted soils and provides novel insights into understanding the interactions among heavy metals, rhizobacteria, and plants.