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Psoriasis, which severely affects the sufferer's life quality, is a chronic skin disease still lacking satisfactory medication. Recently, signal transducer and activator of transcription 3 (STAT3) was revealed playing an important role in the progression of psoriasis. In this paper, a total of 59 quinone derivatives with various scaffolds were designed, synthesized, and evaluated for antipsoriatic potential as STAT3 inhibitors. Among them, 15e was identified as the most potent antipsoriatic agent and could bind to STAT3; reduce both total and phosphorylated STAT3 levels, inhibit the nuclear translocation of STAT3; and, therefore, inhibit the transcription and expression of the propsoriatic factor IL-17A. In vivo experiments on mice showed that the topical application of 15e was effective in alleviating IMQ-induced psoriasis without noticeable side effects. In all, this research rendered 15e as a promising drug candidate for psoriasis.
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Psoriasis is a troublesome scaling skin disease with no high-effective medication available by far. Signal transducer and activator of transcription 3 (STAT3) has recently been revealed as a crucial player in the pathogenesis and progression of psoriasis and emerged as an intriguing antipsoriatic drug target. Naturally occurring lapachol and its quinone analogs had been discovered as effective STAT3 inhibitors, however, their antipsoriatic effects are not well investigated. Previously, we have reported a series of isothiazoloquinone lapachol derivatives. Here, the antipsoriastic potentials of these isothiazoloquinones were investigated and, in addition, 35 novel isoxazoloquinone derivatives were prepared and studied for their anti-psoriasis properties. Among them, the most potent antipsoriatic compound B20 determined by in vitro test on HaCaT cells could directly bind to STAT3, reduce STAT3 level and inhibit STAT3 nuclear translocation. In vivo studies showed that topical application of B20 could effectively alleviate IMQ-induced psoriasis in mice with no obvious side effects. In addition, B20 inhibited the production of interleukin 17 (IL-17A), a STAT3-downstream cytokine essential for the progression of psoriasis, both in vitro and in vivo. Thus, isoxazoloquinone B20 is a potent STAT3-targeting antipsoriatic agent worth of further investigation.
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Objective: Existing studies have reported sustained changes in the cortical structure of rats due to coffee-related factors, which are speculated to occur in the human body. However, there is a lack of research on this topic. Additionally, previous observational studies have found the impact of diseases on cortical structure and the potential therapeutic effects of coffee on these diseases. Our aim was to study the causal effects of coffee-related factors on the human brain using SNPs (single nucleotide polymorphisms). We will connect these discovered causal effects to the impact of diseases on the brain. Through triangulating evidence, we will reveal the potential active areas of coffee in preventing diseases. Methods: We utilized GWAS data from multiple cohorts and their databases, selecting instrumental variables for genetic prediction of coffee intake and plasma levels of caffeine and its direct metabolites. We applied these instrumental variables to individual data on cortical thickness and surface area, as well as hippocampal volume, from the ENIGMA and CHARGE consortium for Mendelian randomization analysis (MR). Triangular evidence was obtained by integrating existing evidence through a specified retrieval strategy, calculating the overlap between coffee's effects on brain regions and disease-related brain regions to identify potential regions of action. Results: The MR analysis yielded 93 positive results for 9 exposures, among which theobromine, a metabolite in the caffeine pathway, was found to be associated with increased hippocampal volume. For cortical structure, theobromine in the caffeine pathway was associated with a decrease in total surface area, while theobromine and caffeine in the pathway were associated with an increase in total thickness. The overlap rate of triangular evidence showed no difference in both overall and subgroup analyses, indicating a high overlap between the effects of coffee on brain regions and disease. Conclusions: From predicted outcomes from causal effects, coffee intake-related factors may have lasting effects on cortical structure. Additionally, theobromine and theophylline have the greatest impact on certain brain gyri, rather than caffeine. Triangulation evidence indicates that disease and coffee intake-related factors act on the same cortical regions, suggesting the presence of potential shared or antagonistic pathways.
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Argininosuccinate synthase (ASS1), a critical enzyme in the urea cycle, acts as a tumor suppressor in many cancers. To date, the anticancer mechanism of ASS1 has not been fully elucidated. Here, we found that phosphoglycerate dehydrogenase (PHGDH), a key rate-limiting enzyme in serine synthesis, is a pivotal protein that interacts with ASS1. Our results showed that ASS1 directly binds to PHGDH and promotes its ubiquitination-mediated degradation to inhibit serine synthesis, consequently suppressing tumorigenesis. Importantly, the tumor suppressive effects of ASS1 were strongly abrogated by PHGDH knockout. In addition, ASS1 knockout and knockdown partially rescued cell proliferation when serine and glycine were depleted, while the inhibitory effect of ASS1 overexpression on cell proliferation was restored by the addition of serine and glycine. These findings unveil a novel role of ASS1 and suggest that the ASS1/PHGDH serine synthesis pathway is a promising target for cancer therapy.
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Argininosuccinato Sintasa , Proliferación Celular , Fosfoglicerato-Deshidrogenasa , Serina , Neoplasias de la Mama Triple Negativas , Fosfoglicerato-Deshidrogenasa/metabolismo , Fosfoglicerato-Deshidrogenasa/genética , Serina/metabolismo , Serina/biosíntesis , Humanos , Femenino , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/genética , Animales , Argininosuccinato Sintasa/metabolismo , Argininosuccinato Sintasa/genética , Línea Celular Tumoral , Ratones Desnudos , Ubiquitinación , Ratones , Glicina/metabolismoRESUMEN
Ginsenosides, the primary bioactive constituents in ginseng (Panax ginseng), possess substantial pharmacological potential and are in high demand in the market. The plant hormone methyl jasmonate (MeJA) effectively elicits ginsenoside biosynthesis in P. ginseng, though the regulatory mechanism remains largely unexplored. NAC transcription factors are critical in intricate plant regulatory networks and participate in numerous plant physiological activities. In this study, we identified a MeJA-responsive NAC transcription factor gene, PgNAC72, from a transcriptome library produced from MeJA-treated P. ginseng callus. Predominantly expressed in P. ginseng flowers, PgNAC72 localizes to the nucleus. Overexpressing PgNAC72 (OE-PgNAC72) in P. ginseng callus notably elevated total saponin levels, particularly dammarane-type ginsenosides, by upregulating dammarenediol synthase (PgDDS), encoding a key enzyme in the ginsenoside biosynthesis pathway. Electrophoretic mobility shift assays and dual-luciferase assays confirmed that PgNAC72 binds to the NAC-binding elements in the PgDDS promoter, thereby activating its transcription. Further RNA-seq and terpenoid metabolomic data in the OE-PgNAC72 line confirmed that PgNAC72 enhances ginsenoside biosynthesis. These findings uncover a regulatory role of PgNAC72 in MeJA-mediated ginsenoside biosynthesis, providing insights into the ginsenoside regulatory network and presenting a valuable target gene for metabolic engineering.
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Acetatos , Regulación de la Expresión Génica de las Plantas , Oxilipinas , Panax , Proteínas de Plantas , Saponinas , Factores de Transcripción , Panax/genética , Panax/metabolismo , Saponinas/biosíntesis , Saponinas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Oxilipinas/metabolismo , Oxilipinas/farmacología , Acetatos/farmacología , Ciclopentanos/metabolismo , Ciclopentanos/farmacología , Ginsenósidos/biosíntesis , Ginsenósidos/metabolismo , Regiones Promotoras Genéticas/genética , Transferasas Alquil y ArilRESUMEN
Orbit angular momentum (OAM) has been considered a new dimension for improving channel capacity in recent years. In this paper, a millimeter-wave broadband multi-mode waveguide traveling-wave antenna with OAM is proposed by innovatively utilizing the transmitted electromagnetic waves (EMWs) characteristic of substrate-integrated gap waveguides (SIGWs) to introduce phase delay, resulting in coupling to the radiate units with a phase jump. Nine "L"-shaped slot radiate elements are cut in a circular order at a certain angle on the SIGW to generate spin angular momentum (SAM) and OAM. To generate more OAM modes and match the antenna, four "Π"-shaped slot radiate units with a 90° relationship to each other are designed in this circular array. The simulation results show that the antenna operates at 28 GHz, with a -10 dB fractional bandwidth (FBW) = 35.7%, ranging from 25.50 to 35.85 GHz and a VSWR ≤ 1.5 dB from 28.60 to 32.0 GHz and 28.60 to 32.0 GHz. The antenna radiates a linear polarization (LP) mode with a gain of 9.3 dBi at 34.0~37.2 GHz, a l = 2 SAM-OAM (i.e., circular polarization OAM (CP-OAM)) mode with 8.04 dBi at 25.90~28.08 GHz, a l = 1 and l = 2 hybrid OAM mode with 5.7 dBi at 28.08~29.67 GHz, a SAM (i.e., left/right hand circular polarization (L/RHCP) mode with 4.6 dBi at 29.67~30.41 GHz, and a LP mode at 30.41~35.85 GHz. In addition, the waveguide transmits energy with a bandwidth ranging from 26.10 to 38.46 GHz. Within the in-band, only a quasi-TEM mode is transmitted with an energy transmission loss |S21| ≤ 2 dB.
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A meta-surface-based arbitrary bandwidth filter realization method for terahertz (THz) future communications is presented. The approach involves integrating a meta-surface-based bandstop filter into an ultra-wideband (UWB) bandpass filter and adjusting the operating frequency range of the meta-surface bandstop filter to realize the design of arbitrary bandwidth filters. It effectively addresses the complexity of designing traditional arbitrary bandwidth filters and the challenges in achieving impedance matching. To underscore its practicality, the paper employs silicon substrate integrated gap waveguide (SSIGW) and this method to craft a THz filter. To begin, design equations for electromagnetic band gap (EBG) structures were developed in accordance with the requirements of through-silicon via (TSV) and applied to the design of the SSIGW. Subsequently, this article employs equivalent transmission line models and equivalent circuits to conduct theoretical analyses for both the UWB passband and the meta-surface stopband portions. The proposed THz filter boasts a center frequency of 0.151 THz, a relative bandwidth of 6.9%, insertion loss below 0.68 dB, and stopbands exceeding 20 GHz in both upper and lower ranges. The in-band group delay is 0.119 ± 0.048 ns. Compared to reported THz filters, the SSIGW filter boasts advantages such as low loss and minimal delay, making it even more suitable for future wireless communication.
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Spinosyn A (SPA), derived from a soil microorganism, Saccharopolyspora spinosa, and its derivative, LM2I, has potential inhibitory effects on a variety of cancer cells. However, the effects of SPA and LM2I in inhibiting the growth of human colorectal cancer cells and the molecular mechanisms underlying these effects are not fully understood. Cell viability was tested by using a 3-(4,5-dimethylthiazol-2-yl-)-2,5-diphenyltetrazolium bromide (MTT) assay and a colony formation assay. On the basis of the IC50 values of SPA and LM2I in seven colorectal cancer (CRC) cell lines, sensitive (HT29 and SW480) and insensitive (SW620 and RKO) cell lines were screened. The GSE2509 and GSE10843 data sets were used to identify 69 differentially expressed genes (DEGs) between sensitive and insensitive cell lines. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interactions (PPI) were performed to elucidate the molecular mechanisms of the DEGs. The hub gene of the DEGs was detected by Western blot analysis and verified using the CRISPR/Cas9 system. Our data indicate that SPA and its derivative LM2I have significant antiproliferative activity in seven colorectal cancer cell lines and colorectal xenograft tumors. On the basis of bioinformatics analysis, it was demonstrated that epidermal growth factor receptor (EGFR) was the hub gene of the DEGs and was associated with the inhibitory effects of SPA and LM2I in CRC cell lines. The study also revealed that SPA and LM2I inhibited the EGFR pathway in vitro and in vivo.
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Neoplasias Colorrectales , Macrólidos , Humanos , Receptores ErbB , Bioensayo , Neoplasias Colorrectales/tratamiento farmacológicoRESUMEN
Viral diseases are a significant risk to the aquaculture industry. Transient receptor potential vanilloid 4 (TRPV4) has been reported to be involved in regulating viral activity in mammals, but its regulatory effect on viruses in teleost fish remains unknown. Here, the role of the TRPV4-DEAD box RNA helicase 1 (DDX1) axis in viral infection was investigated in mandarin fish (Siniperca chuatsi). Our results showed that TRPV4 activation mediates Ca2+ influx and facilitates infectious spleen and kidney necrosis virus (ISKNV) replication, whereas this promotion was nearly eliminated by an M709D mutation in TRPV4, a channel Ca2+ permeability mutant. The concentration of cellular Ca2+ increased during ISKNV infection, and Ca2+ was critical for viral replication. TRPV4 interacted with DDX1, and the interaction was mediated primarily by the N-terminal domain (NTD) of TRPV4 and the C-terminal domain (CTD) of DDX1. This interaction was attenuated by TRPV4 activation, thereby enhancing ISKNV replication. DDX1 could bind to viral mRNAs and facilitate ISKNV replication, which required the ATPase/helicase activity of DDX1. Furthermore, the TRPV4-DDX1 axis was verified to regulate herpes simplex virus 1 replication in mammalian cells. These results suggested that the TRPV4-DDX1 axis plays an important role in viral replication. Our work provides a novel molecular mechanism for host involvement in viral regulation, which would be of benefit for new insights into the prevention and control of aquaculture diseases. IMPORTANCE In 2020, global aquaculture production reached a record of 122.6 million tons, with a total value of $281.5 billion. Meanwhile, frequent outbreaks of viral diseases have occurred in aquaculture, and about 10% of farmed aquatic animal production has been lost to infectious diseases, resulting in more than $10 billion in economic losses every year. Therefore, an understanding of the potential molecular mechanism of how aquatic organisms respond to and regulate viral replication is of great significance. Our study suggested that TRPV4 enables Ca2+ influx and interactions with DDX1 to collectively promote ISKNV replication, providing novel insights into the roles of the TRPV4-DDX1 axis in regulating the proviral effect of DDX1. This advances our understanding of viral disease outbreaks and would be of benefit for studies on preventing aquatic viral diseases.
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ARN Helicasas DEAD-box , Infecciones por Virus ADN , Iridovirus , Canales Catiónicos TRPV , Replicación Viral , Animales , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Infecciones por Virus ADN/veterinaria , Enfermedades de los Peces/virología , Peces , Iridovirus/fisiología , Canales Catiónicos TRPV/genéticaRESUMEN
BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with shorter five-year survival than other breast cancer subtypes, and lacks targeted and hormonal treatment strategies. The signal transducer and activator of transcription 3 (STAT3) signaling is up-regulated in various tumors, including TNBC, and plays a vital role in regulating the expression of multiple proliferation- and apoptosis-related genes. RESULTS: By combining the unique structures of the natural compounds STA-21 and Aulosirazole with antitumor activities, we synthesized a class of novel isoxazoloquinone derivatives and showed that one of these compounds, ZSW, binds to the SH2 domain of STAT3, leading to decreased STAT3 expression and activation in TNBC cells. Furthermore, ZSW promotes STAT3 ubiquitination, inhibits the proliferation of TNBC cells in vitro, and attenuates tumor growth with manageable toxicities in vivo. ZSW also decreases the mammosphere formation of breast cancer stem cells (BCSCs) by inhibiting STAT3. CONCLUSIONS: We conclude that the novel isoxazoloquinone ZSW may be developed as a cancer therapeutic because it targets STAT3, thereby inhibiting the stemness of cancer cells.
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Carbonate and bicarbonate ions are common constituents found in wastewater and natural water matrices, and their impacts on the reactivity of ferrate(VI) (Fe(VI)) with 3,4-dichlorophenol (3,4-DCP) were investigated by determining second-order rate constants of 3,4-DCP removal by Fe(VI) in the presence of CO32- and/or HCO3-. The second-order rate constants decreased from 41.75 to 7.04 M-1 s-1 with an increase of [CO32-] from 0 to 2.0 mM, indicating that CO32- exhibits an inhibitory effect on 3,4-DCP removal kinetics, and experiments on pH effect, radical quenching, and Fe(VI) stability were conducted to explore possible reasons for its effect. Under identical pH conditions, the rate constant in NaOH medium was always higher than in Na2CO3 medium, suggesting that the inhibitory effect partially comes from an increase in alkalinity. Furthermore, the scavenging of hydroxyl radical by carbonate ion also contributed to the inhibitory effect of CO32-. On the other hand, the enhancement effect of CO32- depending on the increase in Fe(VI) stability was found, but did not exceed its inhibitory effect. In addition, 3,4-DCP removal kinetics was not affected by HCO3-, while synergistically inhibited by CO32-/HCO3-. Moreover, 3,4-DCP removal efficiency was substantially suppressed in the presence of CO32-, while the slight enhancement effect of HCO3- and the synergistic inhibitory effect of CO32-/HCO3- were observed. The experimental results clearly demonstrated that carbonate and bicarbonate ions play an important role in the process of 3,4-DCP removal by Fe(VI) and should not be considered only as scavengers.
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Contaminantes Químicos del Agua , Purificación del Agua , Bicarbonatos , Oxidación-Reducción , Carbonatos , Fenoles/análisis , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodosRESUMEN
Background: Methylation modification patterns play a crucial role in human cancer progression, especially in gastrointestinal cancers. We aimed to use methylation regulators to classify patients with gastric adenocarcinoma and build a model to predict prognosis, promoting the application of precision medicine. Methods: We obtained RNA sequencing data and clinical data from The Cancer Genome Atlas (TCGA) database (n=335) and Gene Expression Omnibus (GEO) database (n=865). Unsupervised consensus clustering was used to identify subtypes of gastric adenocarcinoma. We performed functional enrichment analysis, immune infiltration analysis, drug sensitivity analysis, and molecular feature analysis to determine the clinical application for different subtypes. The univariate Cox regression analysis and the LASSO regression analysis were subsequently used to identify prognosis-related methylation regulators and construct a risk model. Results: Through unsupervised consensus clustering, patients were divided into two subtypes (cluster A and cluster B) with different clinical outcomes. Cluster B included patients with a better prognosis outcome and who were more likely to respond to immunotherapy. We then successfully built a predictive model and found five methylation-related genes (CHAF1A, CPNE8, PHLDA3, SPARC, and EHF) potentially significant to the prognosis of patients. The 1-, 3-, and 5-year areas under the curve of the risk model were 0.712, 0.696, and 0.759, respectively. The risk score was an independent prognostic factor and had the highest concordance index among common clinical indicators. Meanwhile, the tumor microenvironment, sensitivity of chemotherapeutic drugs, molecular features, and oncogenic dedifferentiation differed significantly across the risk groups and subtypes. Conclusions: We classified patients with gastric adenocarcinoma based on methylation regulators, which has positive implications for first-line clinical treatment. The prognostic model could predict the prognosis of patients and help to promote the development of precision medicine.
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Breast cancer is one of the most prevalent malignancies with poor prognosis. Inhibition of angiogenesis is becoming a valid and evident therapeutic strategy to treat cancer. Recent studies uncovered the antiangiogenic activity of ZLM-7 (a combretastain A-4 derivative), but the regulatory mechanism is unclear. ZLM-7 treatment was applied in estrogen receptor-positive cell MCF-7, triple-negative breast cancer cell MDA-MB-231 and xenograft models. Transfections were conducted to overexpress or knockdown targeted genes. The gene and protein expressions were measured by qPCR and Western blotting assay, respectively. Cell proliferation and apoptosis were evaluated using the CCK8 method, clone formation assay and flow cytometry. We found that ZLM-7 upregulated 14-3-3 sigma expression but downregulated MDM2 expression in breast cancer cells. ZLM-7 delayed cell proliferation, promoted apoptosis and blocked cell-cycle progression in human breast cancer cells in vitro, while those effects were abolished by 14-3-3 sigma knockdown; overexpression of 14-3-3 sigma reproduced the actions of ZLM-7 on the cell cycle, which could be reversed by MDM2 overexpression. In xenograft models, ZLM-7 treatment significantly inhibited tumor growth while the inhibition was attenuated when 14-3-3 sigma was silenced. Collectively, ZLM-7 could inhibit MDM2 via upregulating 14-3-3 sigma expression, thereby blocking the breast cancer progression.
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It is known that all current cancer therapies can only benefit a limited proportion of patients; thus, molecular classification and prognosis evaluation are critical for correctly classifying breast cancer patients and selecting the best treatment strategy. These processes usually involve the disclosure of molecular information like mutation, expression, and immune microenvironment of a breast cancer patient, which are not been fully studied until now. Therefore, there is an urgent clinical need to identify potential markers to enhance molecular classification, precision prognosis, and therapy stratification for breast cancer patients. In this study, we explored the gene expression profiles of 1,721 breast cancer patients through CIBERSORT and ESTIMATE algorithms; then, we obtained a comprehensive intratumoral immune landscape. The immune cell infiltration (ICI) patterns of breast cancer were classified into 3 separate subtypes according to the infiltration levels of 22 immune cells. The differentially expressed genes between these subtypes were further identified, and ICI scores were calculated to assess the immune landscape of BRCA patients. Importantly, we demonstrated that ICI scores correlate with patients' survival, tumor mutation burden, neoantigens, and sensitivity to specific drugs. Based on these ICI scores, we were able to predict the prognosis of patients and their response to immunotherapy. Together, these findings provide a realistic scenario to stratify breast cancer patients for precision medicine.
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Neoplasias de la Mama , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Mutación , Medicina de Precisión , Pronóstico , Microambiente Tumoral/genéticaRESUMEN
Ginsenoside Rh2 is one of rare panaxidiols extracted from Panax ginseng and a potential estrogen receptor ligand that exhibits moderate estrogenic activity. However, the effect of Rh2 on growth inhibition and its underlying molecular mechanism in human breast cells are not fully understood. In this study, we tested cell viability by MTT and colony formation assays. Cell growth and cell cycle were determined to investigate the effect of ginsenoside Rh2 by flow cytometry. The expressions of estrogen receptors (ERs), TNFα, and apoptosis-related proteins were detected by qPCR and western blot analysis. The mechanisms of ERα and ERß action were determined using transfection and inhibitors. Antitumor effect of ginsenoside Rh2 against MCF-7 cells was investigated in xenograft mice. Our results showed that ginsenoside Rh2 induced apoptosis and G1/S phase arrest in MCF-7 cells. Treatment of cells with ginsenoside Rh2 down-regulated protein levels of ERα, and up-regulated mRNA and protein levels of ERß and TNFα. We also found that ginsenoside Rh2-induced TNFα over-expression is through up-regulation of ERß initiated by ginsenoside Rh2. Furthermore, ginsenoside Rh2 induced MCF-7 cell apoptosis via estrogen receptor ß-TNFα pathway in vivo. These results demonstrate that ginsenoside Rh2 promotes TNFα-induced apoptosis and G1/S phase arrest via regulation of ERß.
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Neoplasias de la Mama , Ginsenósidos , Animales , Femenino , Humanos , Ratones , Apoptosis , Proteínas Reguladoras de la Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Proliferación Celular , Receptor alfa de Estrógeno , Receptor beta de Estrógeno/genética , Ginsenósidos/farmacología , Ligandos , Receptores de Estrógenos , ARN Mensajero , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Ferrate(VI) (Fe(VI)) is utilized as an efficient and environmentally friendly water treatment agent that can be widely used for degradation of (in)organic pollutants in practical applications. However, only a few spectrophotometric methods for Fe(VI) determination were reported. In this study, a novel method for determining trace levels of aqueous Fe(VI) was developed based on the fact that Fe(VI) reacts with iodide at acidic pH to form iodine, which subsequently is treated with starch to yield the blue starch-iodine complex measured spectrophotometrically at 590 nm. The key measurement parameters, including acidic medium, starch dosages, temperature, time, and addition order were optimized to improve the sensitivity of detection. The increase in absorbance at 590 nm was linear with respect to Fe(VI) added (0.022-50 µM). Its sensitivity was determined as (4.61 ± 0.05) × 104 M-1 cm-1, which was higher than that of existing spectrophotometric methods. The principle for Fe(VI) determination was studied by investigating stoichiometry, kinetics, and mechanism of Fe(VI) reaction with iodide. The molar stoichiometry of Fe(VI) with I3- species was determined to be 1:2. The reaction of Fe(VI) with iodide followed a second-order rate law with first order in each reactant and displayed apparent anti-Arrhenius kinetics, then its reaction pathway was proposed as well. Furthermore, the established method was successfully applied to measure Fe(VI) in various environmental water samples. The results show that the proposed approach is simple, convenient, highly reproducible and extremely sensitive, and is also expected to be of use for kinetic studies of Fe(VI) reaction with (in)organic compounds under acidic conditions.
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Yodo , Contaminantes Químicos del Agua , Purificación del Agua , Yoduros/química , Hierro , Cinética , Oxidación-Reducción , Almidón , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodosRESUMEN
Although sharing gestures and gaze can improve AR remote collaboration, most current systems only enable collaborators to share 2D or 3D gestures, and the unimodal HCI interface remains dominant. To address this problem, we describe a novel remote collaborative platform based on 2.5D gestures and gaze (2.5DGG), which supports an expert who collaborates with a worker (e.g., during assembly or training tasks). We investigate the impact of sharing the remote site's 2.5DGG using spatial AR (SAR) remote collaboration in manufacturing. Compared to other systems, there is a key advantage that it can provide more natural and intuitive multimodal interaction based on 2.5DGG. We track the remote experts' gestures and eye gaze using Leap Motion and aGlass, respectively, in a VR space displaying the live video stream of the local physical workspace and visualize them onto the local work scenario by a projector. The results of an exploratory user study demonstrate that 2.5DGG has a clear difference in performance time and collaborative experience, and it is better than the traditional one.
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DDX41 is an intracellular DNA sensor that evokes type I interferon (IFN-I) production via the adaptor stimulator of interferon gene (STING), triggering innate immune responses against viral infection. However, the regulatory mechanism of the DDX41-STING pathway in teleost fish remains unclear. The mandarin fish (Siniperca chuatsi) is a cultured freshwater fish species that is popular in China because of its high market value. With the development of a high-density cultural mode in mandarin fish, viral diseases have increased and seriously restricted the development of aquaculture, such as ranavirus and rhabdovirus. Herein, the role of mandarin fish DDX41 (scDDX41) and its DEAD and HELIC domains in the antiviral innate immune response were investigated. The level of scDDX41 expression was up-regulated following treatment with poly(dA:dT) or Mandarin fish ranavirus (MRV), suggesting that scDDX41 might be involved in fish innate immunity. The overexpression of scDDX41 significantly increased the expression levels of IFN-I, ISGs, and pro-inflammatory cytokine genes. Co-immunoprecipitation and pull-down assays showed that the DEAD domain of scDDX41 recognized the IFN stimulatory DNA and interacted with STING to activate IFN-I signaling pathway. Interestingly, the HELIC domain of scDDX41 could directly interact with the N-terminal of STING to induce the expression levels of IFN-I and ISGs genes. Furthermore, the scDDX41 could enhance the scSTING-induced IFN-I immune response and significantly inhibit MRV replication. Our work would be beneficial to understand the roles of teleost fish DDX41 in the antiviral innate immune response.
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Enfermedades de los Peces , Interferón Tipo I , Ranavirus , Virosis , Animales , Ranavirus/genética , Peces , Inmunidad Innata/genética , ADN , AntiviralesRESUMEN
Ginseng (Panax ginseng C.A. Mey.) is a precious Chinese traditional medicine, for which ginsenosides are the most important medicinal ingredients. Cytochrome P450 enzymes (CYP450) and their primary redox molecular companion NADPH cytochrome P450 reductase (CPR) play a key role in ginsenoside biosynthesis pathway. However, systematic studies of CPR genes in ginseng have not been reported. Numerous studies on ginsenoside synthesis biology still use Arabidopsis CPR (AtCPR1) as a reductase. In this study, we isolated two CPR genes (PgCPR1, PgCPR2) from ginseng adventitious roots. Phylogenetic tree analysis showed that both PgCPR1 and PgCPR2 are grouped in classâ ¡ of dicotyledonous CPR. Enzyme experiments showed that recombinant proteins PgCPR1, PgCPR2 and AtCPR1 can reduce cytochrome c and ferricyanide with NADPH as the electron donor, and PgCPR1 had the highest enzymatic activities. Quantitative real-time PCR analysis showed that PgCPR1 and PgCPR2 transcripts were detected in all examined tissues of Panax ginseng and both showed higher expression in stem and main root. Expression levels of the PgCPR1 and PgCPR2s were both induced after a methyl jasmonate (MeJA) treatment and its pattern matched with ginsenoside accumulation. The present investigation suggested PgCPR1 and PgCPR2 are associated with the biosynthesis of ginsenoside. This report will assist in future CPR family studies and ultimately improving ginsenoside production through transgenic engineering and synthetic biology.
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NADPH-Ferrihemoproteína Reductasa/genética , Panax/enzimología , Secuencia de Aminoácidos , Clonación Molecular , Biología Computacional , Regulación de la Expresión Génica de las Plantas/genética , Modelos Moleculares , NADPH-Ferrihemoproteína Reductasa/metabolismo , FilogeniaRESUMEN
Aquaculture provides important food, nutrition, and income sources for humans. However, aquaculture industry is seriously threatened by viral diseases. Infectious spleen and kidney necrosis virus (ISKNV) disease causes high mortality and economic losses to the fish culture industry in Asia and has been listed as a certifiable disease by the International Epizootic Office. Vaccine development is urgent to control this disease. Here, a gene-deleted live attenuated candidate vaccine (ΔORF022L) against ISKNV with low pathogenicity and high protection was developed. ΔORF022L replicated well in mandarin fish fry-1 cells and showed similar structure with wild-type ISKNV. However, the pathogenicity was significantly lower as 98% of the mandarin fish infected with ΔORF022L survived, whereas all those infected with wild-type ISKNV died. Of importance, 100% of the ΔORF022L-infected fish survived the ISKNV challenge. ΔORF022L induced anti-ISKNV specific antibody response and upregulation of immune-related genes. This work could be beneficial to the control of fish diseases.