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In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP, which triggers STING-dependent immunity. In Drosophila melanogaster, two cGAS-like receptors (cGLRs) produce 3'2'-cGAMP and 2'3'-cGAMP to activate STING. We explored CDN-mediated immunity in 14 Drosophila species covering 50 million years of evolution and found that 2'3'-cGAMP and 3'2'-cGAMP failed to control infection by Drosophila C virus in D. serrata and two other species. We discovered diverse CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including 2'3'-c-di-GMP. This CDN was a more potent STING agonist than cGAMP in D. melanogaster and it also activated a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for understanding the function and regulation of this emerging family of pattern recognition receptors in animal innate immunity.
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Antivirais , Drosophila , Animais , Drosophila melanogaster , GMP Cíclico , MamíferosRESUMO
Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger cG[2'-5']pA[3'-5']p (2'3'-cGAMP) and controls activation of innate immunity in mammalian cells1-5. Animal genomes typically encode multiple proteins with predicted homology to cGAS6-10, but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors that are capable of recognizing divergent molecular patterns and catalysing synthesis of distinct nucleotide second messenger signals. Crystal structures of human and insect cGLRs reveal a nucleotidyltransferase signalling core shared with cGAS and a diversified primary ligand-binding surface modified with notable insertions and deletions. We demonstrate that surface remodelling of cGLRs enables altered ligand specificity and used a forward biochemical screen to identify cGLR1 as a double-stranded RNA sensor in the model organism Drosophila melanogaster. We show that RNA recognition activates Drosophila cGLR1 to synthesize the novel product cG[3'-5']pA[2'-5']p (3'2'-cGAMP). A crystal structure of Drosophila stimulator of interferon genes (dSTING) in complex with 3'2'-cGAMP explains selective isomer recognition, and 3'2'-cGAMP induces an enhanced antiviral state in vivo that protects from viral infection. Similar to radiation of Toll-like receptors in pathogen immunity, our results establish cGLRs as a diverse family of metazoan pattern recognition receptors.
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Drosophila melanogaster/metabolismo , Nucleotídeos Cíclicos/metabolismo , Nucleotidiltransferases/metabolismo , RNA de Cadeia Dupla/metabolismo , Receptores de Reconhecimento de Padrão/metabolismo , Sistemas do Segundo Mensageiro , Sequência de Aminoácidos , Animais , Cristalografia por Raios X , Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/imunologia , Drosophila melanogaster/virologia , Feminino , Humanos , Imunidade Inata , Masculino , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Modelos Moleculares , Nucleotidiltransferases/química , Nucleotidiltransferases/imunologia , RNA de Cadeia Dupla/análise , RNA de Cadeia Dupla/imunologia , Receptores de Reconhecimento de Padrão/química , Receptores de Reconhecimento de Padrão/imunologia , Vírus/imunologiaRESUMO
In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases that is present in both prokaryotes1 and eukaryotes2-5. In bacteria, these enzymes synthesize a range of cyclic oligonucleotides and have recently emerged as important regulators of phage infections6-8. Here we identify two cGAS-like receptors (cGLRs) in the insect Drosophila melanogaster. We show that cGLR1 and cGLR2 activate Sting- and NF-κB-dependent antiviral immunity in response to infection with RNA or DNA viruses. cGLR1 is activated by double-stranded RNA to produce the cyclic dinucleotide 3'2'-cGAMP, whereas cGLR2 produces a combination of 2'3'-cGAMP and 3'2'-cGAMP in response to an as-yet-unidentified stimulus. Our data establish cGAS as the founding member of a family of receptors that sense different types of nucleic acids and trigger immunity through the production of cyclic dinucleotides beyond 2'3'-cGAMP.
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Drosophila melanogaster/imunologia , Nucleotidiltransferases/imunologia , Receptores de Reconhecimento de Padrão/metabolismo , Vírus/imunologia , Sequência de Aminoácidos , Animais , Linhagem Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Drosophila melanogaster/virologia , Feminino , Humanos , Imunidade Inata/genética , Imunidade Inata/imunologia , Ligantes , Masculino , Proteínas de Membrana/metabolismo , Modelos Moleculares , NF-kappa B/metabolismo , Nucleotídeos Cíclicos/metabolismo , Nucleotidiltransferases/classificação , Nucleotidiltransferases/deficiência , Nucleotidiltransferases/metabolismo , RNA de Cadeia Dupla/análise , RNA de Cadeia Dupla/imunologia , RNA de Cadeia Dupla/metabolismo , Receptores de Reconhecimento de Padrão/classificação , Receptores de Reconhecimento de Padrão/deficiência , Receptores de Reconhecimento de Padrão/imunologiaRESUMO
Chronic kidney disease (CKD) is a common cause of morbidity in human immunodeficiency virus (HIV)-positive individuals. HIV infection leads to a wide spectrum of kidney cell damage, including tubular epithelial cell (TEC) injury. Among the HIV-1 proteins, the pathologic effects of viral protein R (Vpr) are well established and include DNA damage response, cell cycle arrest, and cell death. Several in vitro studies have unraveled the molecular pathways driving the cytopathic effects of Vpr in tubular epithelial cells. However, the in vivo effects of Vpr on tubular injury and CKD pathogenesis have not been thoroughly investigated. Here, we use a novel inducible tubular epithelial cell-specific Vpr transgenic mouse model to show that Vpr expression leads to progressive tubulointerstitial damage, interstitial inflammation and fibrosis, and tubular cyst development. Importantly, Vpr-expressing tubular epithelial cells displayed significant hypertrophy, aberrant cell division, and atrophy; all reminiscent of tubular injuries observed in human HIV-associated nephropathy (HIVAN). Single-cell RNA sequencing analysis revealed the Vpr-mediated transcriptomic responses in specific tubular subsets and highlighted the potential multifaceted role of p53 in the regulation of cell metabolism, proliferation, and death pathways in Vpr-expressing tubular epithelial cells. Thus, our study demonstrates that HIV Vpr expression in tubular cells is sufficient to induce HIVAN-like tubulointerstitial damage and fibrosis, independent of glomerulosclerosis and proteinuria. Additionally, as this new mouse model develops progressive CKD with diffuse fibrosis and kidney failure, it can serve as a useful tool to examine the mechanisms of kidney disease progression and fibrosis in vivo.
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Nefropatia Associada a AIDS , Produtos do Gene vpr , Infecções por HIV , HIV-1 , Insuficiência Renal Crônica , Animais , Humanos , Camundongos , Nefropatia Associada a AIDS/genética , Modelos Animais de Doenças , Produtos do Gene vpr/genética , Produtos do Gene vpr/metabolismo , Produtos do Gene vpr/farmacologia , Infecções por HIV/complicações , HIV-1/genética , HIV-1/metabolismo , Proteínas do Vírus da Imunodeficiência Humana , Camundongos Transgênicos , Insuficiência Renal Crônica/complicaçõesRESUMO
With the widespread use combination antiretroviral therapy, there has been a dramatic decrease in HIV-associated nephropathy. However, although the patients living with HIV have low or undetectable viral load, the prevalence of chronic kidney disease (CKD) in this population remains high. Additionally, improved survival is associated with aging-related comorbidities such as diabetes and cardiovascular disease. A faster progression of CKD is associated with concurrent HIV infection and diabetes than with HIV infection or diabetes alone. To explore the potential pathogenic mechanisms that synergistically drive CKD progression by diabetes and HIV infection, we generated a new mouse model with a relatively low expression of HIV-1 proviral genes specifically in podocytes (pod-HIV mice) to better mimic the setting of kidney injury in patients living with HIV. While no apparent kidney phenotypes were observed at baseline in pod-HIV mice, the induction of mild diabetic kidney disease with streptozotocin led to significant worsening of albuminuria, glomerular injury, podocyte loss, and kidney dysfunction as compared to the mice with diabetes alone. Mechanistically, diabetes and HIV-1 synergistically increased the glomerular expression of microRNA-34a (miR-34a), thereby reducing the expression of Sirtuin-1 (SIRT1) deacetylase. These changes were also associated with increased acetylation and activation of p53 and p65 NF-κB and with enhanced expression of senescence and inflammatory markers. The treatment of diabetic pod-HIV mice with the specific Sirtuin-1 agonist BF175 significantly attenuated albuminuria and glomerulopathy. Thus, our study highlights the reduction in Sirtuin-1 as a major basis of CKD progression in diabetic patients living with HIV and suggests Sirtuin-1 agonists as a potential therapy.
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Diabetes Mellitus , Nefropatias Diabéticas , Infecções por HIV , Podócitos , Albuminúria/genética , Animais , Nefropatias Diabéticas/genética , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Glomérulos Renais , CamundongosRESUMO
Antibiotic resistance genes (ARGs) are emerging contaminants that pose a health risk to humans worldwide. Little information on ARGs in bee honey is available. This study profiles ARGs in bee honey samples produced in China, the biggest producer in the world. Of 317 known ARGs encoding resistance to 8 classes of antibiotics, 212 were found in collected honey samples by a real-time quantitative polymerase chain reaction approach. Occurrence frequencies of genes providing resistance to FCA (fluoroquinolone, quinolone, florfenicol, chloramphenicol, and amphenicol) and aminoglycosides were 21.0% and 18.5%, respectively. Frequencies of genes encoding efflux pumps were 42.5% and those of destructase genes 36.6%, indicating that these two mechanisms were predominant for resistance. Nine plasmid-mediated quinolone resistance genes were detected. Of the nine transposase genes known to be involved in antibiotic resistance, eight were found in the samples examined, with tnpA-4, tnpA-5, and tnpA-6 being more abundant. The abundance of the transposase genes was associated with genes conferring resistance to tetracyclines (r = 0.648, p < 0.01), macrolide-lincosamide-streptogramin B (r = 0.642, p < 0.01), FCA (r = 0.517, p < 0.01), and aminoglycosides (r = 0.401, 0.01 < p < 0.05). This is the first study on the abundance and diversity of ARGs in Chinese bee honey products. These findings suggest that bee honey may be a significant source of ARGs that might pose threat to public health. Further research is required to collect more samples in diverse geographic regions in China to make a more comprehensive judgment of ARG in bee honey.
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Antibacterianos , Mel , Animais , Antibacterianos/farmacologia , China , Resistência Microbiana a Medicamentos , Genes Bacterianos , TetraciclinasRESUMO
Budgerigar fledgling disease virus (BFDV) infection causes sudden death, abdominal distention, and feather abnormality in psittacine birds. In this study, we developed a TaqMan Real-time PCR assay to detect BFDV by targeting a conserved region in VP1 gene. The detection limit of the assay was 30 DNA gene copies, 1000 times more sensitive than conventional PCR. The coefficients of variation were less than 1.09% in either intra- or inter-assays, indicating high reproducibility. By using this method, the prevalence of BFDV in China was evaluated. 56 feces samples were collected from four psittacine birds breeding facilities in China. The results showed 28 out of 56 samples were positive for BFDV in Real-Time PCR assay, while only 19 samples were positive in PCR assay. Three facilities were positive for BFDV with positive rates from 60% to 87.5%. Further sequence analysis of VP1 genes from the positive samples indicated that VP1 genes fell into two different lineages in phylogenetic tree, suggesting that different genotypes BFDV are co-circulating in China.
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Melopsittacus/virologia , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/veterinária , Polyomavirus/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/veterinária , Animais , Fezes/virologia , Infecções por Polyomavirus/virologia , Vigilância da População , Padrões de Referência , Reprodutibilidade dos Testes , Infecções Tumorais por Vírus/virologiaRESUMO
PURPOSE: To explore the impact of subtropical maritime monsoon climate on the frequency of ambulance use for trauma patients in a coastal region in China. METHOD: Statistical analysis of data on ambulance use from the 120 Emergency Command Center in Shantou City, Guangdong Province, from January to December 2012 as well as daily meteorological data from a Shantou observatory was performed to determine how climatic factors (seasons, time, and weather) affect the frequency of ambulance use for trauma patients. RESULTS: The daily ambulance use for trauma patients differed between spring and summer or autumn (p<0.05), between sunny and rainy days (p<0.05), and between cloudy and lightly or moderately rainy days (p<0.05).We found a linear correlation between daily maximum temperature and daily ambulance use for trauma patients (R² =0.103, p<0.05). In addition, there was significant difference in ambulance use between good and bad weather (p<0.05). CONCLUSION: Frequency of ambulance use for trauma patients is affected by the subtropical maritime monsoon climate in the coastal region. Better weather contributes to increased daily frequency of ambulance use, which is the highest in autumn and lowest in spring.
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Ambulâncias , Clima , Ferimentos e Lesões/terapia , China , Humanos , Estudos RetrospectivosRESUMO
Neuropilin-1 (NRP-1) is a nontyrosine kinase coreceptor for semaphorin 3A and the vascular endothelial growth factor involved in tumor angiogenesis, growth, and metastasis and is regarded as a promising target for cancer therapy. In the present study, we investigated the effects of an anti-NRP-1 monoclonal antibody (mAb) that we generated for MCF7 breast cancer cellular adhesion studies. MTT, colony formation, and adhesion assays showed that our anti-NRP-1 mAb dose-dependently inhibited MCF7 proliferation and fibronectin adhesion, leading to a rounded cellular morphology. Further, rhodamine phalloidin stain revealed that fibronectin-dependent formation of actin stress fibers was inhibited by anti-NRP-1 mAb. Immunoprecipitation and western blot showed that anti-NRP-1 mAb treatment inhibited the formation of NRP-1-α5ß1 integrin complexes and suppressed the phosphorylation of focal adhesion kinase and p130cas in MCF7 cells. These findings contribute to further understanding the NRP-1 function in cell adhesion and tumor metastasis. Moreover, our anti-NRP-1 mAb is a prospective drug candidate for tumor treatment.
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Anticorpos Monoclonais/farmacologia , Neoplasias da Mama/patologia , Adesão Celular/efeitos dos fármacos , Proteína Substrato Associada a Crk/metabolismo , Fibronectinas/fisiologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Neuropilina-1/metabolismo , Actinas/metabolismo , Anticorpos Monoclonais/isolamento & purificação , Feminino , Humanos , Células MCF-7 , Neuropilina-1/imunologia , Transdução de SinaisRESUMO
Visible light-triggered photochemical reactions in aqueous media are highly valuable to tailor molecular structures and properties in an ecofriendly manner. Here we report visible light-induced catalyst-free [2 + 2] cycloadditions of thermoresponsive dendronized styryltriazines, which show tunable microconfinement to guest dyes in aqueous media. These dendronized styryltriazines are constituted of conjugated mono- or tristyryltriazines, which carry hydrophilic dendritic oligoethylene glycol (OEG) pendants. They underwent efficient [2 + 2] cycloadditions to form dendronized cyclobutane dimers or oligomers in water through irradiation with visible light of 400 nm, and their cycloaddition behavior was dominated by dendritic architectures and solvent conditions. Dendronization with dendritic OEGs also afforded them characteristic thermoresponsive properties with tunable phase transition temperatures in the range 36-65 °C, which can be further modulated through photocycloaddition of styryltriazine chromophores. Importantly, dendronized styryltriazines can form tunable microenvironments in aqueous media, which encapsulate hydrophobic solvatochromic Nile red to exhibit variable photophysical properties. The encapsulated guest dye can be simultaneously released through noninvasive visible light-induced [2 + 2] cycloaddition reactions.
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Complex optical elements have the advantages of improving image quality and optical performance and expanding the field of view. Therefore, it is widely used in X-ray scientific devices, adaptive optical elements, high-energy laser systems, and other fields and is a hot research direction in precision optics. Especially for precision machining, there is a greater need for high-precision testing technology. However, how to measure complex surfaces efficiently and accurately is still an important research topic in optical metrology technology. In order to verify the ability of optical metrology for complex optical surfaces with wavefront sensing based on image information of the focal plane, some experiment platforms in different types of optical surfaces were set up. In order to validate the feasibility and validity of wavefront-sensing technology based on image information of focal planes, a large number of repetitive experiments were carried out. The measurement results with wavefront sensing based on image information of the focal plane were compared with the measurement results with the ZYGO interferometer. The experimental results demonstrate that good agreement is obtained among the error distribution, PV value, and RMS value of the ZYGO interferometer, which shows the feasibility and validity of wavefront sensing based on image information of focal plane technology in optical metrology for the complex optical surface.
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In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP. This CDN binds to and activates the protein STING to trigger immunity. We recently discovered in the model organism Drosophila melanogaster two cGAS-like receptors (cGLRs) that activate STING-dependent antiviral immunity and can produce 3'2'-cGAMP, in addition to 2'3'-cGAMP. Here we explore CDN-mediated immunity in 14 different Drosophila species covering 50 million years of evolution and report that 2'3'-cGAMP and 3'2'-cGAMP fail to control infection by Drosophila C virus in D. serrata, D. sechellia and D. mojavensis . Using an accurate and sensitive mass spectrometry method, we discover an unexpected diversity of CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster , including a novel CDN, 2'3'-c-di-GMP. We show that 2'3'-c-di-GMP is the most potent STING agonist identified so far in D. melanogaster and that this molecule also activates a strong antiviral transcriptional response in D. serrata . Our results shed light on the evolution of cGLRs in flies and provide a basis for the understanding of the function and regulation of this emerging family of PRRs in animal innate immunity.
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Metformin acts as an energy regulator by activating 5'-adenosine monophosphate-activated protein kinase (AMPK), which is a key player in the regulation of energy homeostasis, but it is uncertain whether AMPK is its direct target. This study aims to investigate the possible interaction between metformin and AMPK. First, we verified that metformin can promote AMPK activation and induce ACC inactivation in human HepG2 cells using western blot. Then we predicted that metformin may interact with the γ subunit of AMPK by molecular docking analysis. The fluorescence spectrum and ForteBio assays indicated that metformin has a stronger binding ability to the γ subunit of AMPK than to α subunit. In addition, interaction of metformin with γ-AMPK resulted in a decrease in the α-helicity determined by CD spectra, but relatively little change was seen with α-AMPK. These results demonstrate that metformin may interact with AMPK through binding to the γ subunit.
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Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Hipoglicemiantes/farmacocinética , Metformina/farmacocinética , Ativação Enzimática/efeitos dos fármacos , Células Hep G2 , Humanos , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Ligação Proteica/efeitos dos fármacosRESUMO
The manufacturing process is defined by the synchronous matching and mutual support of the event logic and the task context, so that the work task can be completed perfectly, by executing each step of the manufacturing process. However, during the manufacturing process of the traditional production environment, on-site personnel are often faced with the situation that on-site advice is required, due to a lack of experience or knowledge. Therefore, the function of the manufacturing process should be more closely connected with the workers and tasks. To improve the manufacturing efficiency and reduce the error rate, this research proposes a set of manufacturing work knowledge frameworks, to integrate the intelligent assisted learning system into the manufacturing process. Through Augmented Reality (AR) technology, object recognition technology is used to identify the components within the line of sight, and the assembly steps are presented visually. During the manufacturing process, the system can still feedback to the user in animation, so as to achieve the function equivalent to on-the-spot guidance and assistance when a particular problem is solved by a specialist. Research experiments show that the operation of this intelligent assisted learning interface can more quickly recognize how the manufacturing process works and can solve problems, which greatly resolves the issue of personnel with insufficient experience and knowledge.
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OBJECTIVE: Renal impairment is a significant complication of systemic lupus erythematosus (SLE). Additionally, infection in patients with end-stage renal disease (ESRD) attributable to SLE is common, and it increases the risk of mortality. This study explored the infection profile and risk factors for mortality in patients with ESRD attributable to SLE. METHODS: In this retrospective, observational study of 125 hospitalized patients, demographic, clinical, laboratory, treatment, and prognosis data were retrieved and analyzed. RESULTS: The 125 cases included 98 pulmonary infections (78.4%), 14 urinary infections (11.2%), and 13 intestinal infections (10.4%). Twenty-six patients died within 1 month after enrollment. Univariate Cox regression and Kaplan-Meier analyses revealed several possible indicators potentially influencing patient survival. Furthermore, multivariate Cox regression analysis identified a higher SLE Disease Activity Index-2000 score, recent higher-dose glucocorticoid use, hypertension, and catheter indwelling as risk factors for higher mortality. CONCLUSIONS: Infections were common in patients with advanced SLE and ESRD, and several risk factors might increase the risk of mortality. Once infection is identified, empiric antibiotics should be initiated immediately, and subsequent antibiotics should be applied per the results of drug sensitivity testing to clear the infection.
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Falência Renal Crônica , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Antibacterianos , Humanos , Falência Renal Crônica/etiologia , Lúpus Eritematoso Sistêmico/complicações , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The apoptosis of podocytes is a characteristic event in diabetic nephropathy. The aim of this study was to investigate whether microRNAs (miRNAs) affect podocyte apoptosis in diabetic circumstances. METHODS: Diabetic nephropathy was induced in DBA/2 mice by intraperitoneal injections of streptozotocin, and the levels of proteinuria were measured with ELISA. Apoptosis-related miRNAs were screened in isolated glomeruli. A conditionally immortalized mouse podocyte cell line was cultured in 25 mMD-glucose and either transfected with miRNA-195 (miR-195) mimics or inhibitors. The levels of BCL2 and caspase expression were determined using real-time RT-PCR and Western blot analysis, respectively. We also measured WT-1 and synaptopodin in podocytes. Apoptosis of podocytes was assessed with Hoechst 33258 nuclear staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry. RESULTS: The expression of miR-195 was elevated in both diabetic mice with proteinuria and podocytes that were cultured in high glucose. Transfection with miR-195 reduced the protein levels of BCL2 and contributed to podocyte apoptosis via an increase in caspase-3. miR-195-treated podocytes underwent actin rearrangement and failed to synthesize sufficient levels of WT-1 and synaptopodin proteins, which suggests that the cells had suffered injuries similar to those observed in diabetic nephropathy in both humans and animal models. CONCLUSIONS: Taken together, our findings demonstrate that miR-195 promotes apoptosis of podocytes under high-glucose conditions via enhanced caspase cascades for BCL2 insufficiency. This work thus presents a meaningful approach for deciphering mechanisms, by which miRNAs participate in diabetic renal injury.
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Caspases/metabolismo , Regulação Enzimológica da Expressão Gênica , MicroRNAs/metabolismo , Podócitos/citologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Animais , Apoptose , Sequência de Bases , Compostos de Bifenilo/farmacologia , Bisbenzimidazol/farmacologia , Citometria de Fluxo/métodos , Humanos , Marcação In Situ das Extremidades Cortadas , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos DBA , Dados de Sequência Molecular , Nitrofenóis/farmacologia , Piperazinas/farmacologia , Processamento Pós-Transcricional do RNA , Homologia de Sequência do Ácido Nucleico , Sulfonamidas/farmacologiaRESUMO
The plastic deformation processes and fracture behavior of a Ti-5Al-5Mo-5V-1Cr-1Fe alloy with bimodal and lamellar microstructures were studied by room-temperature tensile tests with in situ scanning electron microscopy (SEM) observations. The results indicate that a bimodal microstructure has a lower strength but higher ductility than a lamellar microstructure. For the bimodal microstructure, parallel, deep slip bands (SBs) are first noticed in the primary α (αp) phase lying at an angle of about 45° to the direction of the applied tension, while they are first observed in the coarse lath α (αL) phase or its interface at grain boundaries (GBs) for the lamellar microstructure. The ß matrix undergoes larger plastic deformation than the αL phase in the bimodal microstructure before fracture. Microcracks are prone to nucleate at the αp/ß interface and interconnect, finally causing the fracture of the bimodal microstructure. The plastic deformation is mainly restricted to within the coarse αL phase at GBs, which promotes the formation of microcracks and the intergranular fracture of the lamellar microstructure.
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Fenghwaia, a new monotypic genus, along with the new species Fenghwaia gardeniicarpa, is described from Guangdong Province, China. The combined features of inferior ovary, cylindrical drupaceous fruits and orbicular and dorsiventrally-compressed seeds with an elongate and pronounced basal appendage make the new genus significantly different from other genera of the family. In addition, its pollen morphology also showed great similarity to other species of this stenopalynous family. The molecular phylogenetic analysis, based on nuclear ribosomal internal transcribed spacer (ITS) and plastid trnL-F intron spacer (trnL-F) DNA sequence data from the new genus and the other 375 species representing 58 genera of Rhamnaceae, indicates that Fenghwaia is nested within the 'rhamnoid' group and sister to the tribe Rhamneae and then both sister to the tribe Maesopsideae. A taxonomic classification key to the 'rhamnoid' group is provided, based on morphological characters. A global conservation assessment is also performed and classifies Fenghwaia gardeniicarpa as Near Threatened (NT).
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Lightweight Al2NbTi3V2Zrx (x = 1.0, 0.8, 0.6, 0.4, 0.2, 0) high entropy alloys are produced by mechanical milling and vacuum hot pressing. The microstructure, phase evolution and mechanical properties of the alloys are analyzed. The microstructure of the alloys with x = 1.0, 0.8, 0.6 consists of BCC solid solution matrix and two intermetallics (i.e., α and ß), and then ß phase disappears in Al2NbTi3V2Zr0.4 alloy. Further decreasing Zr content to below 0.2, α phase vanishes and γ and δ intermetallics emerge in Al2NbTi3V2Zr0.2 and Al2NbTi3V2 alloys. The Al2NbTi3V2Zrx alloys cannot obtain a single phase structure by decreasing Zr content with current fabrication process, which is likely because that the mixing entropy of the HEA system is not large enough to prohibit the formation of the secondary phases at hot pressing temperature of 1250 °C. All the bulks possess low density ranging from 4.93 to 5.21 g/cm3. Hardness of the Al2NbTi3V2Zrx alloys decreases from 781 HV to 697 HV and then increases to 814 HV with the decrease of Zr from x = 1 to 0. This varying tendency is closely related with the content of secondary intermetallic phases. The compressive test shows the Al2NbTi3V2Zr0.4 alloy has a yield strength of 1742 MPa, fracture strength of 2420 MPa, compressive strain of 38.2 %, which is probably related to its simplest microstructure. The comprehensive mechanical property of Al2NbTi3V2Zr0.4 alloy is superior to the majority of other HEAs and Ti64 alloy.
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High-efficiency nanotheranostic agents with multimodal imaging guidance have attracted considerable interest in the field of cancer therapy. Herein, novel silver-decorated bismuth-based heterostructured polyvinyl pyrrolidone nanoparticles (NPs) with good biocompatibility (Bi-Ag@PVP NPs) were synthesized for accurate theranostic treatment, which can integrate computed tomography (CT)/photoacoustic (PA) imaging and photodynamic therapy/photothermal therapy (PDT/PTT) into one platform. The Bi-Ag@PVP NPs can enhance light absorption and achieve a better photothermal effect than bismuth NPs. Moreover, after irradiation under an 808 nm laser, the Bi-Ag@PVP NPs can efficiently induce the generation of reactive oxygen species (ROS), thereby synergizing PDT/PTT to exert an efficient tumor ablation effect both in vitro and in vivo. Furthermore, Bi-Ag@PVP NPs can also be employed to perform enhanced CT/PA imaging because of their high X-ray absorption attenuation and enhanced photothermal conversion. Thus, they can be utilized as a highly effective CT/PA imaging-guided nanotheranostic agent. In addition, an excellent antibacterial effect was achieved. After irradiation under an 808 nm laser, the Bi-Ag@PVP NPs can destroy the integrity of Escherichia coli, thereby inhibiting E. coli growth, which can minimize the risk of infection during cancer therapy. In conclusion, our study provides a novel nanotheranostic platform that can achieve CT/PA-guided PDT/PTT synergistic therapy and have potential antibacterial properties. Thus, this work provides an effective strategy for further broad clinical application prospects.