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Lateral branches are important components of shoot architecture and directly affect crop yield and production cost. Although sporadic studies have implicated abscisic acid (ABA) biosynthesis in axillary bud outgrowth, the function of ABA catabolism and its upstream regulators in shoot branching remain elusive. Here, we showed that the MADS-box transcription factor AGAMOUS-LIKE 16 (CsAGL16) is a positive regulator of axillary bud outgrowth in cucumber (Cucumis sativus). Functional disruption of CsAGL16 led to reduced bud outgrowth, whereas overexpression of CsAGL16 resulted in enhanced branching. CsAGL16 directly binds to the promoter of the ABA 8'-hydroxylase gene CsCYP707A4 and promotes its expression. Loss of CsCYP707A4 function inhibited axillary bud outgrowth and increased ABA levels. Elevated expression of CsCYP707A4 or treatment with an ABA biosynthesis inhibitor largely rescued the Csagl16 mutant phenotype. Moreover, cucumber General Regulatory Factor 1 (CsGRF1) interacts with CsAGL16 and antagonizes CsAGL16-mediated CsCYP707A4 activation. Disruption of CsGRF1 resulted in elongated branches and decreased ABA levels in the axillary buds. The Csagl16 Csgrf1 double mutant exhibited a branching phenotype resembling that of the Csagl16 single mutant. Therefore, our data suggest that the CsAGL16-CsGRF1 module regulates axillary bud outgrowth via CsCYP707A4-mediated ABA catabolism in cucumber. Our findings provide a strategy to manipulate ABA levels in axillary buds during crop breeding to produce desirable branching phenotypes.
Assuntos
Ácido Abscísico , Cucumis sativus , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/genética , Cucumis sativus/metabolismo , Ácido Abscísico/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Brotos de Planta/genética , Reguladores de Crescimento de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Plantas Geneticamente Modificadas , Sistema Enzimático do Citocromo P-450RESUMO
GGGGCC (G4C2) hexanucleotide repeat expansion (HRE) in the first intron of the chromosome 9 open reading frame 72 (C9ORF72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Among the five dipeptide repeat proteins translated from G4C2 HRE, arginine-rich poly-PR (proline:arginine) is extremely toxic. However, the molecular mechanism responsible for poly-PR-induced cell toxicity remains incompletely understood. Here, we found that poly-PR overexpression triggers severe DNA damage in cultured cells, primary cortical neurons, and the motor cortex of a poly-PR transgenic mouse model. Interestingly, we identified a linkage between poly-PR and RNA-binding protein fused in sarcoma (FUS), another ALS-related gene product associated with DNA repair. Poly-PR interacts with FUS both in vitro and in vivo, phase separates with FUS in a poly-PR concentration-dependent manner, and impairs the fluidity of FUS droplets in vitro and in cells. Moreover, poly-PR impedes the recruitment of FUS and its downstream protein XRCC1 to DNA damage foci after microirradiation. Importantly, overexpression of FUS significantly decreased the level of DNA damage and dramatically reduced poly-PR-induced cell death. Our data suggest the severe DNA damage caused by poly-PR and highlight the interconnection between poly-PR and FUS, enlightening the potential therapeutic role of FUS in alleviating poly-PR-induced cell toxicity.
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Esclerose Lateral Amiotrófica , Demência Frontotemporal , Animais , Camundongos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Expansão das Repetições de DNA , Demência Frontotemporal/genética , Demência Frontotemporal/metabolismo , Proteínas/genética , Dano ao DNA/genética , Arginina/genética , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Dipeptídeos/genéticaRESUMO
Epigenetic dysregulation that leads to alterations in gene expression and is suggested to be one of the key pathophysiological factors of Parkinson's disease (PD). Here, we found that α-synuclein preformed fibrils (PFFs) induced histone H3 dimethylation at lysine 9 (H3K9me2) and increased the euchromatic histone methyltransferases EHMT1 and EHMT2, which were accompanied by neuronal synaptic damage, including loss of synapses and diminished expression levels of synaptic-related proteins. Furthermore, the levels of H3K9me2 at promoters in genes that encode the synaptic-related proteins SNAP25, PSD95, Synapsin 1 and vGLUT1 were increased in primary neurons after PFF treatment, which suggests a linkage between H3K9 dimethylation and synaptic dysfunction. Inhibition of EHMT1/2 with the specific inhibitor A-366 or shRNA suppressed histone methylation and alleviated synaptic damage in primary neurons that were treated with PFFs. In addition, the synaptic damage and motor impairment in mice that were injected with PFFs were repressed by treatment with the EHMT1/2 inhibitor A-366. Thus, our findings reveal the role of histone H3 modification by EHMT1/2 in synaptic damage and motor impairment in a PFF animal model, suggesting the involvement of epigenetic dysregulation in PD pathogenesis.
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Transtornos Motores , Doença de Parkinson , Animais , Camundongos , Histonas/metabolismo , Metilação , Neurônios/metabolismo , alfa-Sinucleína/metabolismoRESUMO
BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.
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Circuncisão Masculina , Infecções por HIV , Homossexualidade Masculina , Humanos , Masculino , Adulto , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , China/epidemiologia , Incidência , Comportamento Sexual , Análise de Intenção de TratamentoRESUMO
A fast and sensitive direct extraction (DE) method developed in our group can efficiently extract proteins in 30 min from a 5 cm-long hair strand. Previously, we coupled DE to downstream analysis using gel electrophoresis followed by in-gel digestion, which can be time-consuming. In searching for a better alternative, we found that a combination of DE with a bead-based method (SP3) can lead to significant improvements in protein discovery in human hair. Since SP3 is designed for general applications, we optimized it to process hair proteins following DE and compared it to several other in-solution digestion methods. Of particular concern are genetically variant peptides (GVPs), which can be used for human identification in forensic analysis. Here, we demonstrated improved GVP discovery with the DE and SP3 workflow, which was 3 times faster than the previous in-gel digestion method and required significantly less instrument time depending on the number of gel slices processed. Additionally, it led to an increased number of identified proteins and GVPs. Among the tested in-solution digestion methods, DE combined with SP3 showed the highest sequence coverage, with higher abundances of the identified peptides. This provides a significantly enhanced means for identifying proteins and GVPs in human hair.
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Peptídeos , Proteínas , Humanos , Proteínas/análise , Peptídeos/análise , Eletroforese , Cabelo/química , Cabelo/metabolismoRESUMO
Reproducibility is a "proteomic dream" yet to be fully realized. A typical data analysis workflow utilizing extracted ion chromatograms (XICs) often treats the information path from identification to quantification as a one-way street. Here, we propose an XIC-centric approach in which the data flow is bidirectional: identifications are used to derive XICs whose information is in turn applied to validate the identifications. In this study, we employed liquid chromatography-mass spectrometry data from glycoprotein and human hair samples to illustrate the XIC-centric concept. At the core of this approach was XIC-based monoisotope repicking. Taking advantage of the intensity information for all detected isotopes across the whole range of an XIC peak significantly improved the accuracy and uncovered misidentifications originating from monoisotope assignment mistakes. It could also rescue non-top-ranked glycopeptide hits. Identification of glycopeptides is particularly susceptible to precursor mass errors for their low abundances, large masses, and glycans differing by 1 or 2 Da easily confused as isotopes. In addition, the XIC-centric strategy significantly reduced the problem of one XIC peak associated with multiple unique identifications, a source of quantitative irreproducibility. Taken together, the proposed approach can lead to improved identification and quantification accuracy and, ultimately, enhanced reproducibility in proteomic data analyses.
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Cabelo , Proteômica , Proteômica/métodos , Humanos , Cromatografia Líquida/métodos , Cabelo/química , Reprodutibilidade dos Testes , Glicoproteínas/análise , Glicoproteínas/química , Glicopeptídeos/análise , Glicopeptídeos/química , Análise de Dados , Espectrometria de Massas/métodos , Espectrometria de Massas em Tandem/métodosRESUMO
We report the comparison of mass-spectral-based abundances of tryptic glycopeptides to fluorescence abundances of released labeled glycans and the effects of mass and charge state and in-source fragmentation on glycopeptide abundances. The primary glycoforms derived from Rituximab, NISTmAb, Evolocumab, and Infliximab were high-mannose and biantennary complex galactosylated and fucosylated N-glycans. Except for Evolocumab, in-source ions derived from the loss of HexNAc or HexNAc-Hex sugars are prominent for other therapeutic IgGs. After excluding in-source fragmentation of glycopeptide ions from the results, a linear correlation was observed between fluorescently labeled N-glycan and glycopeptide abundances over a dynamic range of 500. Different charge states of human IgG-derived glycopeptides containing a wider variety of abundant attached glycans were also investigated to examine the effects of the charge state on ion abundances. These revealed a linear dependence of glycopeptide abundance on the mass of the glycan with higher charge states favoring higher-mass glycans. Findings indicate that the mass spectrometry-based bottom-up approach can provide results as accurate as those of glycan release studies while revealing the origin of each attached glycan. These site-specific relative abundances are conveniently displayed and compared using previously described glycopeptide abundance distribution spectra "GADS" representations. Mass spectrometry data are available from the MAssIVE repository (MSV000093562).
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Imunoglobulina G , Espectrometria de Massas em Tandem , Humanos , Glicosilação , Glicopeptídeos/análise , Polissacarídeos/química , ÍonsRESUMO
MafA and c-Maf are close members of the Maf transcription factor family and indicators of poor prognosis of multiple myeloma (MM). Our previous study finds that the ubiquitin ligase HERC4 induces c-Maf degradation but stabilizes MafA, and the mechanism is elusive. In the present study, we find that HERC4 interacts with MafA and mediates its K63-linked polyubiquitination at K33. Moreover, HERC4 inhibits MafA phosphorylation and its transcriptional activity triggered by glycogen synthase kinase 3ß (GSK3ß). The K33R MafA variant prevents HERC4 from inhibiting MafA phosphorylation and increases MafA transcriptional activity. Further analyses reveal that MafA can also activate the STAT3 signaling, but it is suppressed by HERC4. Lastly, we demonstrate that lithium chloride, a GSK3ß inhibitor, can upregulate HERC4 and synergizes dexamethasone, a typical anti-MM drug, in inhibiting MM cell proliferation and xenograft growth in nude mice. These findings thus highlight a novel regulation of MafA oncogenic activity in MM and provide the rationale by targeting HERC4/GSK3ß/MafA for the treatment of MM.
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Glicogênio Sintase Quinase 3 beta , Fatores de Transcrição Maf Maior , Mieloma Múltiplo , Poliubiquitina , Ubiquitina-Proteína Ligases , Ubiquitinação , Animais , Humanos , Camundongos , Proliferação de Células , Dexametasona/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Cloreto de Lítio/farmacologia , Fatores de Transcrição Maf Maior/antagonistas & inibidores , Fatores de Transcrição Maf Maior/metabolismo , Camundongos Nus , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Fosforilação , Poliubiquitina/metabolismo , Fator de Transcrição STAT3/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.
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The intriguing photonic spin Hall effect (PSHE) of reflected Laguerre-Gaussian (LG) beams can be exhibited on the systems with optical anti-parity-time (Anti-PT) symmetry. During the reflection, the left/right circularly polarized (LCP/RCP) components of reflected LG beams are considered. By controlling parameters of the Anti-PT systems, the PSHE of reflected LCP/RCP can be identical and symmetrical with respect to incident-reflected plane (IRP). Due to gain/non-Hermitian effects of designed Anti-PT systems, special PSHE near the strong gain points (SGP) and exceptional points (EPs) can be obtained simulatively. Through analyses in PSHE of reflected LCP on four similar Anti-PT systems, specific conclusions that can even be extended to more general cases. Moreover, simulations of PSHE by simultaneously varying the incident angles * and imaginary/real dielectric constants Im/Re[ε] of the Anti-PT systems, specal PSHE and other novel optical phenomena with real applications can be revealed. So Anti-PT systems not only provide novel ways to regulate the PSHE of reflected LG beams, but also offer possibilities for new optical characteristics of devices.
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Fiber side-pump couplers can enhance the output power of fiber laser due to their dependable and efficient operation and impressive power handling capability. We developed a tellurite fiber side-pump coupler by twisting and fusing a tapered pump fiber onto a target fiber. The effect of twisting parameters on coupling efficiency was comprehensively investigated through theoretical simulations and experiments. Experimental results exhibited an impressive coupling efficiency of 76.5% and a root mean square stability of 0.086% and 0.091% before and after one month, respectively, driven by an incident pump power of up to 4.2 W.
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In this Letter, we have proposed a particle manipulation system based on a polarization-dependent dielectric metasurface (PDM), which enables far-field trapping and 2D arbitrary transporting. Based on flexible phase manipulation, by tuning the size and angle of meta-atoms, polarization-selective focusing in different modules of the metasurface can be realized. Then, when those regional focuses are continuously lighted in a relay way, the trapped particle at the focus could be delivered to the next one. When six different characteristic polarization states are tuned in order, the trapped particle could be transported to any adjacent hot spots so that 2D manipulation can be realized in an extended range. With the consideration of the Brownian motion, our simulation results show that the success rate of the particle transport can reach more than 96.0%, even after 20 periods when excited at the wavelength of 1064â nm with a power density of 0.15â mW/µm2. We believe that our research provides a new and promising method for particle manipulation and furthers on-chip optofluidic applications.
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In this Letter, a surface wave, the Pearcey Talbot-like plasmon, which has the properties of self-imaging and multiple autofocusing, is presented as a novel, to the best of our knowledge, plasmonic bottle array generation scheme. With originality, the overall structure and the partial intensity of the plasmonic bottle array can be adjusted through the initial input, and modifying the Pearcey function enables the plasmonic bottle array to exhibit self-bending characteristics, which makes particle capture and manipulation easier and more flexible. A scheme to generate the plasmon is proposed, and we prove it by the finite-difference time-domain numerical simulations.
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BACKGROUND: Postoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs. METHODS: The clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis. RESULTS: Preoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups. CONCLUSIONS: Preoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.
Assuntos
Craniofaringioma , Diabetes Insípido Neurogênico , Neoplasias Hipofisárias , Complicações Pós-Operatórias , Humanos , Craniofaringioma/cirurgia , Craniofaringioma/sangue , Craniofaringioma/complicações , Feminino , Masculino , Estudos Retrospectivos , Adulto , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/complicações , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Adolescente , Pessoa de Meia-Idade , Criança , Adulto Jovem , Diabetes Insípido Neurogênico/sangue , Diabetes Insípido Neurogênico/etiologia , Neutrófilos , Biomarcadores/sangue , Linfócitos , Inflamação/sangue , Contagem de Leucócitos , Período Pré-Operatório , Pré-Escolar , Prognóstico , Curva ROCRESUMO
To objectively quantify changes in steroid hormones in organisms caused by adverse environmental loads, we developed a simple and sensitive UPLC-MS/MS (ultra-performance liquid chromatography triple quadrupole mass spectrometry) method for the simultaneous determination of 18 steroid hormones on the HPG axis. This analytical method was based on liquid extraction and a multimode electrospray and atmospheric pressure chemical ionization (ESCi) source, which was optimized by mass spectrometry, liquid phase and pretreatment for the quantification of cholesterol (CH), aldosterone (A), cortisone (E), hydrocortisone (F), 21-deoxycortisol (21-DF), corticosterone (B), 11-deoxycortisol (11-DF), androstenedione (A2), estradiol (E2), estrone (E1), 2-methoxyestradiol (2-MeE2), 21-hydroxyprogesterone (21-OHP), 17-α hydroxyprogesterone (17α-OHP), testosterone (T), dehydroepiandrosterone (DHEA), progesterone (P4), dihydrotestosterone (DHT), and pregnenolone (P5). The method exhibits linearity in the analyte-concentration range 0.03-1000 µg mL-1 (r2 > 0.99), the spiked recoveries for the concentration range tested are 76.22-113.66%, and the relevant parameters of precision are 7.52-1.14%. Compared to other methods, this new method not only uses a small amount of serum (only 100 µL), but also permits the analysis of the challenging steroid, cholesterol. Furthermore, the method was successfully applied to the determination of steroids in Mus musculus, Carassius auratus, Rana catesbeiana Shaw, and Rana nigromaculata serum samples from randomly selected individuals. Therefore, this method is efficient and a very useful tool for assessing changes in steroid hormones.
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Upregulation of ADAMTS-4 has been reported to have an important role in lung injury, and ADAMTS-4 expression is regulated by miR-126a-5p in abdominal aortic aneurysms. The aim of this study was to investigate whether miR-126a-5p/ADAMTS-4 plays a role in influenza-virus-induced lung injury. Lung fibroblasts were infected with H1N1 influenza virus to detect changes in miR-126a-5p and ADAMTS-4 expression, and cell viability was measured by CCK-8 assay. Inflammatory factors and matrix protease levels were examined using ELISA kits, and cell apoptosis was assessed by measuring the levels of apoptosis-related proteins. A dual luciferase assay was used to verify the regulatory relationship between miR-126a-5p and ADAMTS-4. H1N1 influenza virus reduced fibroblast viability, inhibited miR-126a-5p expression, and promoted ADAMTS-4 expression. Overexpression of miR-126a-5p attenuated the cellular inflammatory response, apoptosis, matrix protease secretion, and virus replication. Luciferase reporter assays revealed that miR-126a-5p inhibited ADAMTS-4 expression by targeting ADAMTS-4 mRNA. Further experiments showed that overexpression of ADAMTS-4 significantly reversed the inhibitory effects of miR-126a-5p on fibroblast inflammation, apoptosis, matrix protease secretion, and virus replication. Upregulation of miR-126a-5p inhibits H1N1-induced apoptosis, inflammatory factors, and matrix protease secretion, as well as virus replication in lung fibroblasts.
Assuntos
Proteína ADAMTS4 , Apoptose , Fibroblastos , Inflamação , Vírus da Influenza A Subtipo H1N1 , Pulmão , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Fibroblastos/virologia , Fibroblastos/metabolismo , Humanos , Pulmão/virologia , Pulmão/patologia , Proteína ADAMTS4/genética , Proteína ADAMTS4/metabolismo , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/fisiologia , Inflamação/genética , Sobrevivência Celular , Replicação Viral , Influenza Humana/virologia , Influenza Humana/genética , Influenza Humana/metabolismo , Linhagem CelularRESUMO
Four undescribed coumarin derivatives, ficusalt A (1) and ficusalt B (2), a pair of racemic coumarins, (±) ficudimer A (3a/3b), along with ten known amides, were isolated from the roots of Ficus hirta. Their structures were elucidated by several spectroscopic data analyses, including HRESIMS, NMR, and X-ray single-crystal diffraction. The cytotoxic activities of all compounds against HeLa, HepG2, MCF-7, and H460 cell lines were detected using the MTT assay. Among these, 5 showed the highest activity against HeLa cells. Subsequently, the apoptotic, anti-invasive, and anti-migration effects of 5 on HeLa cells were determined by flow cytometer, transwell invasion assay, and wound-healing assay, respectively. The result suggested that 5 distinctly induced the apoptosis in HeLa cells and inhibited their invasion and migration. Further studies on anticancer mechanisms were conducted using Western blotting. As a result, 5 increased the cleavage of PARP and the expression of pro-apoptotic protein Bax. Moreover, 5 notably upregulated the phosphorylation of p38 and JNK, whereas inhibited the expression of p-ERK and p-AKT. Our results demonstrated that 5 could be a potential leading compound for further application in the treatment of cervical cancer.
Assuntos
Antineoplásicos , Ficus , Feminino , Humanos , Células HeLa , Ficus/química , Amidas/farmacologia , Cumarínicos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , ApoptoseRESUMO
In this study, a novel sulfur/zinc co-doped biochar (SZ-BC) stabilizer was successfully developed for the remediation of mercury-contaminated soil. Results from SEM, TEM, FTIR and XRD revealed that biochar (BC) was successfully modified by sulfur and zinc. In the batch adsorption experiments, the sulfur-zinc co-pyrolysis biochar displayed excellent Hg(II) adsorption performance, with the maximum adsorption capacity of SZ-BC (261.074â¯mg/g) being approximately 16.5 times that of BC (15.855â¯mg/g). Laboratory-scale static incubation, column leaching, and plant pot experiments were conducted using biochar-based materials. At an additional dosage of 5â¯% mass ratio, the SZ-BC exhibits the most effective stabilization of mercury in soil, leading to a significant reduction in leaching loss compared to the control group (CK) by 51.30â¯%. Following 4 weeks of incubation and 2 weeks of leaching with SZ-BC, the residual mercury in the soil increased by 27.84â¯%. As a result, potential ecological risk index of mercury decreased by 92â¯% compared to the CK group. In the pot experiment, SZ-BC significantly enhanced the growth of Chinese cabbage, with biomass and root dry weight reaching 3.20 and 2.80 times that of the CK group, respectively. Additionally, the Translocation Factor (TF) and Bioconcentration Factor (BF) were reduced by 44.86â¯% and 74.43â¯%, respectively, in the SZ-BC group compared to the CK group. Moreover, SZ-BC can effectively improve enzyme activities and increase microbial communities in mercury-contaminated soils. The mechanisms of adsorption and stabilization were elucidated through electrostatic adsorption, ion exchange, surface complexation, and precipitation. These findings provide a potentially effective material for stabilizing soils contaminated with mercury.
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Carvão Vegetal , Recuperação e Remediação Ambiental , Mercúrio , Poluentes do Solo , Enxofre , Zinco , Carvão Vegetal/química , Mercúrio/química , Poluentes do Solo/química , Zinco/química , Recuperação e Remediação Ambiental/métodos , Adsorção , Enxofre/química , Solo/química , Brassica/química , Biodegradação AmbientalRESUMO
A lateral flow assay (LFA) strip based on dual 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB)-encoded satellite Fe3O4@Au (Mag@Au) SERS tags with nanogap is reported for ultrasensitive and simultaneous diagnosis of two SARS-CoV-2 functional proteins. Composed of Fe3O4 core, satellite gold shell with nanogaps, and double-layer DTNB, the Mag@Au nanoparticles with an average size of 238 nm were designed as multifunctional tags to efficiently enrich the target SARS-CoV-2 protein from complex samples, significantly enhancing the SERS signal of the LFA strip and provide quantitative SERS detection of analyte on test lines. The developed dual DTNB-encoded satellite Mag@Au-based LFA allowed simultaneous quantification of spike (S) protein and nucleocapsid (NP) protein with detection limits of 23 pg mL-1 and 2 pg mL-1, respectively, lower than commercial ELISA kits and reported SERS-LFA detection system-based Au NPs and Fe3O4@3 nm Au MNPs. This magnetic SERS-LFA also showed high performance of multi-variant strain detection and further distinguished clinical samples of Omicron variant infection, demonstrating the potential of in situ detection of respiratory virus diseases.
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COVID-19 , Nanopartículas Metálicas , Humanos , COVID-19/diagnóstico , Ácido Ditionitrobenzoico , Ouro , SARS-CoV-2RESUMO
CeO2 nanorod based catalysts for the base-free synthesis of azoxy-aromatics via transfer hydrogenation of nitroarenes with ethanol as hydrogen donor have been synthesized and investigated. The oxygen vacancies (Ov ) and base sites are critical for their excellent catalytic properties. The Ov , i.e., undercoordinated Ce cations, serve as the sites to activate ethanol and nitroarenes by lowering the energy barrier to transfer hydrogen from α-Csp3 -H in ethanol to the nitro group coupling it to the redox reactions between Ce3+ and Ce4+ . At the same time, the base sites catalyze the condensation step to selectively produce azoxy-aromatics. The catalytic route opens a much improved way to use non-noble metal oxides without additives for the selective functional group reduction and coupling reactions.