RESUMEN
Proton exchange membranes (PEMs) play an important role in fuel cells. For realizing a nanofiber (NF) structure design in PEMs, the material should have tunable pores and a high specific area. In this study, we attempt to design a novel NF with synergistic architecture doped MOF for constructing three-dimensional (3D) proton conduction networks in PEMs. In this framework, UiO-66-COOH serves as a platform for proton sites to synergistically promote proton conductivity via polyvinylpyrrolidone dissolution, hydrolyzation of polyacrylonitrile, and sulfamic acid functionalization of the shell-layer NF. Benefiting from enriched proton-transfer sites in NFs, the obtained composite membrane overcomes the trade-off among proton conductivity, methanol permeability, and mechanical stability. The composite membrane with 50 % fiber (Nafion/S@NF-50) exhibited a high proton conductivity of 0.212 S cm-1 at 80 °C and 100 % relative humidity, suppressed methanol permeability of 0.66 × 10-7 cm2 s-1, and the maximum power density of direct methanol fuel cell is 182.6 mW cm-2. Density functional theory was used to verify the important role of sulfamic acid in proton transfer, and the activation energy barriers under anhydrous and hydrous conditions are only 0.337 and 0.081 kcal, respectively. This study opens up new pathways for synthesizing NF composite PEMs.
RESUMEN
Synthetic biology is rapidly evolving into a data-intensive science that increasingly relies on massive data sets; one of its applications is the evaluation of the economic viability of fermentation processes. However, the key economic indicators, namely titer, rate, and yield (TRY), which respectively reflect the downstream processing, reactor size, and raw material costs, are not well captured in bioinformatics databases. In this paper, we present BioTRY, an intuitive and user-friendly tool that contains >5,000 biochemicals and >3,800 strains, along with over 52,000 corresponding TRY entries with original references. It is freely available at http://www.synbiohealth.cn/biotry. To our knowledge, BioTRY is the first available database on biosynthesis TRY data from original research. We anticipate that BioTRY will become a useful tool that aids researchers and decision-makers in understanding the current development state of biosynthesis and allows them to foresee potential prospects and applications for biosynthesis.
RESUMEN
Exploring novel electrochemiluminescence (ECL) co-reaction accelerators to construct ultrasensitive sensing systems is a prominent focus for developing advanced ECL sensors. However, challenges still remain in finding highly efficient accelerators and understanding their promoting mechanisms. In this paper, ZIF-67@MXene nanosheet composites, with highly conductive in-plane structure and confined-stable pore/channel, are designed to act as high-efficient co-reaction accelerators and achieve a significant enhancement in the luminol-H2O2 based ECL system. Mechanism investigation suggests that hydroxyl radicals (·OH) and singlet oxygen (1O2) can be selectively and preferentially generated on ZIF-67@MXene due to the stable and efficient absorption of ·OH and 1O2, leading to a remarkable enhancement in the ECL efficiency of luminol (830%). Finally, by designing a plasmonic NH2-MIL-88@Pd nanozyme, an "on-off" switch immunosensor is constructed for the detection of prostate-specific antigen (PSA). Based on the multiple signal amplification effect, the linear detection range for PSA is expanded by three orders of magnitude. The detection limit is also improved from 1.44 × 10-11 to 9.1 × 10-13 g mL-1. This work proposes an effective method for the preparation of highly efficient co-reaction accelerators and provides a new strategy for the sensitive detection of cancer markers.
RESUMEN
Fruit color is a key feature of fruit quality, primarily influenced by anthocyanin or carotenoid accumulation or chlorophyll degradation. Adapting the pigment content is crucial to improve the fruit's nutritional and commercial value. Genetic factors along with other environmental components (i.e., light, temperature, nutrition, etc.) regulate fruit coloration. The fruit coloration process is influenced by plant hormones, which also play a vital role in various physiological and biochemical metabolic processes. Additionally, phytohormones play a role in the regulation of a highly conserved transcription factor complex, called MBW (MYB-bHLH-WD40). The MBW complex, which consists of myeloblastosis (MYB), basic helix-loop-helix (bHLH), and WD40 repeat (WDR) proteins, coordinates the expression of downstream structural genes associated with anthocyanin formation. In fruit production, the application of plant hormones may be important for promoting coloration. However, concerns such as improper concentration or application time must be addressed. This article explores the molecular processes underlying pigment formation and how they are influenced by various plant hormones. The ABA, jasmonate, and brassinosteroid increase anthocyanin and carotenoid formation, but ethylene, auxin, cytokinin, and gibberellin have positive as well as negative effects on anthocyanin formation. This article establishes the necessary groundwork for future studies into the molecular mechanisms of plant hormones regulating fruit color, ultimately aiding in their effective and scientific application towards fruit coloration.
Asunto(s)
Antocianinas , Frutas , Regulación de la Expresión Génica de las Plantas , Reguladores del Crecimiento de las Plantas , Reguladores del Crecimiento de las Plantas/metabolismo , Frutas/genética , Frutas/metabolismo , Antocianinas/metabolismo , Pigmentación/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Carotenoides/metabolismo , ColorRESUMEN
BACKGROUND AND AIMS: Hemostatic powder (HP) is a novel hemostasis modality for nonvariceal GI bleeding. This meta-analysis was performed to evaluate the efficacy of HP monotherapy versus conventional endoscopic treatment (CET) for nonvariceal GI bleeding. METHODS: PubMed, EMBASE, and Cochrane Library databases were systematically searched from inception to October 16, 2023. The primary outcomes were the initial hemostatic rate and the 30-day recurrent bleeding rate. After the meta-analysis, a trial sequential analysis (TSA) was also conducted to decrease the risk of random errors and validate the result. RESULTS: The meta-analysis included 8 studies, incorporating 653 patients in total. Given significant heterogeneity, all analyses were segregated into malignancy-related and nonmalignancy-related GI bleeding lesions. For the former, HP monotherapy significantly improved the initial hemostasis rate and 30-day recurrent bleeding rate compared with CET (relative risk [RR], 1.50; 95% confidence interval [CI], 1.28-1.75; P < .001; RR, .32; 95% CI, .12-.86; P = .02, respectively), and TSA supported the results. For nonmalignancy-related GI bleeding, HP monotherapy and CET have similar initial hemostasis and 30-day recurrent bleeding rates (RR, 1.08; 95% CI, .98-1.19; P = .11; RR, 1.15; 95% CI, .46-2.90; P = .76, respectively), but the TSA failed to confirm the results. CONCLUSIONS: HP monotherapy surpassed CET in terms of the initial hemostasis rate and 30-day recurrent bleeding rate for patients with malignancy-related GI bleeding. However, their relative efficacy for nonmalignancy-related GI bleeding remains unresolved.
RESUMEN
The Named Data Networking (NDN) is currently an important future network framework, and the mobility issue of producers within NDN is a primary challenge. However, in environments characterized by frequent producers mobility, traditional producer mobility support schemes still encounter issues such as excessive consumer delays and interest packet loss. With the development of The 6th generation communication technology (6G), integrating ground networks with satellites has emerged as a potential solution to address the aforementioned problems. In this paper, we propose an NDN producer mobility support scheme based on multi-satellite data depot, named MsDD. The proposed scheme proactively caches producer data into a data depot built on a low-earth orbit satellite constellation to minimize the impact of NDN producer mobility on network performance. We design data depot construction strategy, in-network caching strategy, and routing strategy based on forwarding hint to facilitate effective communication in satellite networks. Experimental results using ndnSIM demonstrate that compared with other existing schemes, MsDD can effectively shield the impact of producer mobility on consumer delay, delivery ratio, and signaling overhead, and MsDD has a clear advantage in terms of consumer delay and delivery ratio.
Asunto(s)
Redes de Comunicación de Computadores , Algoritmos , Tecnología Inalámbrica , Comunicaciones por SatéliteRESUMEN
The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors.
Asunto(s)
Clorhidrato de Duloxetina , Ratones Desnudos , Sertralina , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Sertralina/farmacología , Sertralina/farmacocinética , Clorhidrato de Duloxetina/farmacología , Clorhidrato de Duloxetina/farmacocinética , Masculino , Humanos , Ratones , Ratas , Línea Celular Tumoral , Pirazoles/farmacocinética , Pirazoles/farmacología , Ratas Sprague-Dawley , Interacciones Farmacológicas , Quinoxalinas/farmacocinética , Quinoxalinas/farmacología , Quinoxalinas/administración & dosificación , Ratones Endogámicos BALB CRESUMEN
Microplastics (MPs) mainly enter the human body through ingestion and breathing. Most of them are excreted through feces, and only a small amount can accumulate in human organs and tissues. In contrast, if intravenous injection contains MPs, it could directly enter bloodstream and maybe pose severe health risk. To verify this hypothesis, we collected two types of injection [0.9 % NaCl and 5 % Glucose] with three dominant brands in China, to analyze the possible MPs. The results indicated that the injection had an average abundance of 895 MP particles/kg, ranging from 140 to 1840 particles/kg. Furthermore, more MPs were found in NaCl than Glucose injection. The MPs encompassed 21 types of polymers with notable brand variations in distribution. Notably, polyisoprene chlorinated (61.77 % in NaCl, 61.23 % in Glucose) are most prevalent. Most polymers had small diameter, with 30.5 % and 44.2 % of particles measuring between 0 and 30 µm in NaCl and Glucose injection, respectively. These minute particle sizes contribute to the dispersal of MPs within human tissues. In terms of shape, most polymers are fibers/fragments, with some in bead form. Our study uncovered a previously unnoticed but important pathway for MPs enter the human body, emphasizing the need to evaluate health risks of infusion-related MP.
RESUMEN
Inosine 5'-monophosphate dehydrogenase (IMPDH), known as GuaB in bacteria, catalyzes the rate-limiting step in de novo guanine biosynthesis and is conserved from humans to bacteria. We developed a series of potent inhibitors that selectively target GuaB over its human homolog. Here, we show that these GuaB inhibitors are bactericidal, generate phenotypic signatures that are distinct from other antibiotics, and elicit different time-kill kinetics and regulatory responses in two important Gram-negative pathogens: Acinetobacter baumannii and Escherichia coli. Specifically, the GuaB inhibitor G6 rapidly kills A. baumannii but only kills E. coli after 24 h. After exposure to G6, the expression of genes involved in purine biosynthesis and stress responses change in opposite directions while siderophore biosynthesis is downregulated in both species. Our results suggest that different species respond to GuaB inhibition using distinct regulatory programs and possibly explain the different bactericidal kinetics upon GuaB inhibition. The comparison highlights opportunities for developing GuaB inhibitors as novel antibiotics.IMPORTANCEA. baumannii is a priority bacterial pathogen for which development of new antibiotics is urgently needed due to the emergence of multidrug resistance. We recently developed a series of specific inhibitors against GuaB, a bacterial inosine 5'-monophosphate dehydrogenase, and achieved sub-micromolar minimum inhibitory concentrations against A. baumannii. GuaB catalyzes the rate-limiting step of de novo guanine biosynthesis and is highly conserved across bacterial pathogens. This study shows that inhibition of GuaB induced a bacterial morphological profile distinct from that of other classes of antibiotics, highlighting a novel mechanism of action. Moreover, our transcriptomic analysis showed that regulation of de novo purine biosynthesis and stress responses of A. baumannii upon GuaB inhibition differed significantly from that of E. coli.
Asunto(s)
Acinetobacter baumannii , Antibacterianos , Inhibidores Enzimáticos , Escherichia coli , IMP Deshidrogenasa , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/genética , Acinetobacter baumannii/enzimología , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , Escherichia coli/metabolismo , IMP Deshidrogenasa/antagonistas & inhibidores , IMP Deshidrogenasa/metabolismo , IMP Deshidrogenasa/genética , Antibacterianos/farmacología , Inhibidores Enzimáticos/farmacología , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismoRESUMEN
Cadmium (Cd) is readily absorbed by tobacco and accumulates in the human body through smoke inhalation, posing threat to human health. While there have been many studies on the negative impact of cadmium in tobacco on human health, the specific adaptive mechanism of tobacco roots to cadmium stress is not well understood. In order to comprehensively investigate the effects of Cd stress on the root system of tobacco, the combination of transcriptomic, biochemical, and physiological methods was utilized. In this study, tobacco growth was significantly inhibited by 50 µM of Cd, which was mainly attributed to the destruction of root cellular structure. By comparing the transcriptome between CK and Cd treatment, there were 3232 up-regulated deferentially expressed genes (DEGs) and 3278 down-regulated DEGs. The obvious differential expression of genes related to the nitrogen metabolism, metal transporters and the transcription factors families. In order to mitigate the harmful effects of Cd, the root system enhances Cd accumulation in the cell wall, thereby reducing the Cd content in the cytoplasm. This result may be mediated by plant hormones and transcription factor (TF). Correlational statistical analysis revealed significant negative correlations between IAA and GA with cadmium accumulation, indicated by correlation coefficients of -0.91 and -0.93, respectively. Conversely, ABA exhibited a positive correlation with a coefficient of 0.96. In addition, it was anticipated that 3 WRKY TFs would lead to a reduction in Cd accumulation. Our research provides a theoretical basis for the systematic study of the specific physiological processes of plant roots under Cd stress.
Asunto(s)
Cadmio , Reguladores del Crecimiento de las Plantas , Factores de Transcripción , Transcriptoma , Cadmio/toxicidad , Cadmio/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Transcriptoma/efectos de los fármacos , Reguladores del Crecimiento de las Plantas/metabolismo , Nicotiana/genética , Nicotiana/efectos de los fármacos , Estrés Fisiológico , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacosRESUMEN
Guanine nucleotides are required for growth and viability of cells due to their structural role in DNA and RNA, and their regulatory roles in translation, signal transduction, and cell division. The natural antibiotic mycophenolic acid (MPA) targets the rate-limiting step in de novo guanine nucleotide biosynthesis executed by inosine-5´-monophosphate dehydrogenase (IMPDH). MPA is used clinically as an immunosuppressant, but whether in vivo inhibition of bacterial IMPDH (GuaB) is a valid antibacterial strategy is controversial. Here, we describe the discovery of extremely potent small molecule GuaB inhibitors (GuaBi) specific to pathogenic bacteria with a low frequency of on-target spontaneous resistance and bactericidal efficacy in vivo against Acinetobacter baumannii mouse models of infection. The spectrum of GuaBi activity includes multidrug-resistant pathogens that are a critical priority of new antibiotic development. Co-crystal structures of A. baumannii, Staphylococcus aureus, and Escherichia coli GuaB proteins bound to inhibitors show comparable binding modes of GuaBi across species and identifies key binding site residues that are predictive of whole-cell activity across both Gram-positive and Gram-negative clades of Bacteria. The clear in vivo efficacy of these small molecule GuaB inhibitors in a model of A. baumannii infection validates GuaB as an essential antibiotic target. IMPORTANCE: The emergence of multidrug-resistant bacteria worldwide has renewed interest in discovering antibiotics with novel mechanism of action. For the first time ever, we demonstrate that pharmacological inhibition of de novo guanine biosynthesis is bactericidal in a mouse model of Acinetobacter baumannii infection. Structural analyses of novel inhibitors explain differences in biochemical and whole-cell activity across bacterial clades and underscore why this discovery may have broad translational impact on treatment of the most recalcitrant bacterial infections.
Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , IMP Deshidrogenasa , Acinetobacter baumannii/efectos de los fármacos , Animales , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , IMP Deshidrogenasa/antagonistas & inhibidores , IMP Deshidrogenasa/metabolismo , Modelos Animales de Enfermedad , Pruebas de Sensibilidad Microbiana , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/genética , Descubrimiento de Drogas , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Femenino , Farmacorresistencia Bacteriana MúltipleRESUMEN
The fruit of the jujube tree is high in nutrients and has various health benefits. China is a major producer of jujube, and it is now cultivated all around the world. Numerous studies have demonstrated the nutritional value and potential health advantages of bioactive compounds found in the jujube tree. Furthermore, the jujube tree has a remarkable 7000-year agricultural history. The jujube plant has developed a rich gene pool, making it a valuable resource for germplasm. Different studies have focused on the developmental stages of jujube fruits to identify the optimal time for harvest and to assess the changes in their bioactive natural compounds or products during the process of development but the molecular mechanism underlying the production of bioactive natural products in Z. jujuba is still poorly understood. Moreover, the potential differential expressed genes (DEGs) identified as responsible for the synthesis of these compounds should be further functionally verified. It has been noticed that the contents of total flavonoids, total phenolic, and vitamin C increase significantly during the ripening process, while the contents of soluble sugars and organic acids decrease gradually. In this review, we have also scrutinized the challenges that hinder the utilization of jujube fruit resources and suggested potential areas for further research. As such, our review serves as a valuable resource for the future development of jujube-based nutritional compounds and the incorporation of their nutritional elements into the functional foods industry.
RESUMEN
Phytoplasmas can induce complex and substantial phenotypic changes in their hosts in ways that favour their colonisation, but the mechanisms underlying these changes remain largely unknown. Jujube witches' broom (JWB) disease is a typical phytoplasma disease causing great economic loss in Chinese jujube (Ziziphus jujuba Mill.). Here, we reported an effector, PHYL1JWB from Candidatus Phytoplasma ziziphi, which implicated in inducing abnormal floral organogenesis. Utilising a combination of in vivo and in vitro methods, we investigated the influence of PHYL1JWB on the proteins associated with floral development. Our findings reveal that PHYL1JWB facilitates the proteasome-mediated degradation of essential flower morphogenetic regulators, including AP1, SEP1, SEP2, SEP3, SEP4, CAL, and AGL6, through a distinctive pathway that is dependent on the activity of the 26S proteasome, thus obviating the requirement for lysine ubiquitination of the substrates. Further, the Y2H analysis showed that the leucine at position 75th in second α helix of PHYL1JWB is fundamental for the interactions of PHYL1JWB with AP1 and SEP1-4 in jujube and Arabidopsis. Our research carry profound implications for elucidating the contribution of PHYL1JWB to the aberrant floral development in diseased jujube, and help to establish a robust theoretical underpinning for the prophylaxis and therapy of JWB disease.
RESUMEN
Proposed is a Satellite network cache placement strategy (PNCCP) based on popularity and node cooperation to address the issue of significant delays in end-to-end connectivity due to instability among satellites. Initially, the strategy employs spectral clustering algorithm to partition the satellite network's topology, limiting the retrieval scope of content and reducing unnecessary propagation delays. Within each partition, a cache collaboration open mechanism among satellites is devised to share cache resources, utilizing the proximity of neighboring nodes to share popular content and cache space. Furthermore, the data naming network (NDN) cache model is enhanced and integrated with the open mechanism, with an update mechanism designed to address the invalidation caused by the dynamic nature of satellite networks. Finally, aiming to minimize users' average retrieval delay, the artificial bee colony algorithm is employed to solve the optimal cache placement problem. Simulation results demonstrate that compared to three contrasting cache strategies, the proposed strategy reduces user content retrieval delays, improves cache hit rates, and holds an advantage in reducing request hop counts.
Asunto(s)
Algoritmos , Redes de Comunicación de Computadores , Simulación por Computador , Humanos , Modelos TeóricosRESUMEN
A bioinformatics analysis was conducted to screen for relevant expression datasets of the transcription factor SRF knockout mice. The aim was to investigate the relationship between SRF and m6A-related genes, predict how SRF regulates the m6A modification of GEM genes mediated by METTL3, and explore potential molecular mechanisms associated with neurotrauma. Disease gene databases such as GeneCards, DisGeNET, and Phenolyzer, and transcription factor databases TFDB and TRRUST, were used to obtain epilepsy-related genes and transcription factors. The intersection was then selected. Expression data of SRF knockout epilepsy mice were obtained from the GEO database and used to filter differentially expressed genes. Important module genes related to the disease were selected through WGCNA co-expression analysis. The intersection between these genes and the differentially expressed genes was performed, followed by PPI network analysis and GO/KEGG enrichment analysis. Furthermore, the core genes were selected using the cytoHubba plugin of the Cytoscape software. Differential expression analysis was performed on m6A-related factors in the GEO dataset, and the relationship between SRF and m6A-related factors and core genes was analyzed. The m6A binding sites of SRF with the METTL3 promoter and target gene Gem were predicted using the AnimalTFDB and SRAMP websites, respectively. We found that the transcription factor SRF may be a key gene in epilepsy during neuronal development. Further WGCNA analysis showed that 129 module genes were associated with SRF knockout epilepsy, and these differentially expressed genes were mainly enriched in the neuroactive ligand-receptor interaction pathway. The final results indicate that knocking out SRF may inhibit the transcription of METTL3, thereby inhibiting the m6A modification of Gem and leading to upregulation of Gem expression, thereby playing an important role in neuronal damage. Knocking out the SRF gene may inhibit the transcription of m6A methyltransferase METTL3, thereby inhibiting the m6A modification of GEM genes mediated by METTL3, promoting GEM gene expression, and leading to the occurrence of epilepsy-related neuron injury. Further investigation revealed that SRF overexpression can potentially enhance the transcription of METTL3, thus promoting m6A modification of GEM, resulting in downregulation of GEM expression. This process regulates oxidative stress in epileptic mouse neurons, suppresses inflammatory responses, and mitigates associated damage. Additionally, an in vitro neuronal epileptic model was established, and experimental techniques such as qRT-PCR and WB were employed to assess the expression of SRF, METTL3, and GEM in hippocampal tissues and neurons. The experimental results were consistent with our predictions, demonstrating that overexpression of SRF can inhibit the development of epilepsy-related neuronal damage. This study reveals that knockout of the SRF gene may suppress the transcription of m6A methyltransferase METTL3, thereby inhibiting m6A modification of the GEM gene mediated by METTL3 and subsequently promoting the expression of the GEM gene, leading to the occurrence of epilepsy-related neuronal damage.
RESUMEN
A series of pyrimidine-2,4-diamine analogues were designed and synthesized. Their anticancer activity and the underlying mechanism against colorectal cancer (CRC) HCT116 cells and non-small cell lung cancer (NSCLC) A549 cells were investigated. The results demonstrated that the active compound Y18 significantly inhibited cancer cell proliferation by inducing robust cell cycle arrest and cell senescence through the persistence of DNA damage. Additionally, Y18 exhibited significant inhibitory effects on the adhesion, migration and invasion of cancer cells in vitro. Mechanistically, Y18 achieved these anticancer activities by suppressing GTSE1 transcription and expression. Y18 also effectively inhibited tumor growth in vivo with minimal side effects. Furthermore, Y18 exhibited a suitable half-life and oral bioavailability (16.27%), with limited inhibitory activity on CYP isoforms. Taken together, these results suggested that Y18 could be a potential chemotherapeutic drug for cancer treatment, particularly in cases of GTSE1 overexpressed cancers.
Asunto(s)
Antineoplásicos , Proliferación Celular , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Pirimidinas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Pirimidinas/química , Pirimidinas/farmacología , Pirimidinas/síntesis química , Relación Estructura-Actividad , Estructura Molecular , Animales , Descubrimiento de Drogas , Ratones , Movimiento Celular/efectos de los fármacos , Diaminas/química , Diaminas/farmacología , Diaminas/síntesis química , Ratones DesnudosRESUMEN
Silicon (Si) can significantly improve the salt tolerance of plants, but its mechanism remains unclear. In this study, role of abscisic acid (ABA) in Si derived salt resistance in tobacco seedling was investigated. Under salt stress, the photosynthetic rate, stomatal conductance, and transpiration rate of tobacco seedlings were reduced by 86.17%, 80.63%, and 67.54% respectively, resulting in a decrease in biomass. The application of Si found to mitigate these stress-induced markers. However, positive role of Si was mainly attributed to the enhanced expression of aquaporin genes, which helped in enhancing root hydraulic conductance (Lpr) and ultimately maintaining the leaf relative water content (RWC). Moreover, sodium tungstate, an ABA biosynthesis inhibitor, was used to test the role of ABA on Si-regulating Lpr. The results indicated that the improvement of Lpr by Si was diminished in the presence of ABA inhibitor. In addition, it was observed that the ABA content was increased due to the Si-upregulated of ABA biosynthesis genes, namely NtNCED1 and NtNCED5. Conversely, the expression of ABA metabolism gene NtCYP7O7A was found to be reduced by Si. Together, this study suggested that Si increased ABA content, leading to enhanced efficiency of water uptake by the roots, ultimately facilitating an adequate water supply to maintain leaf water balance. As a result, there was an improvement in salt resistance in tobacco seedling.
Asunto(s)
Ácido Abscísico , Acuaporinas , Regulación de la Expresión Génica de las Plantas , Nicotiana , Tolerancia a la Sal , Silicio , Nicotiana/metabolismo , Nicotiana/genética , Nicotiana/efectos de los fármacos , Ácido Abscísico/metabolismo , Silicio/farmacología , Silicio/metabolismo , Acuaporinas/metabolismo , Acuaporinas/genética , Tolerancia a la Sal/genética , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Plantones/metabolismo , Plantones/efectos de los fármacos , Plantones/genética , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de los fármacosRESUMEN
In this article, we investigated the solitary wave solutions of the KdV-mKdV equation using Hirota's bilinear method. Closed-form analytical single and multiple solitary wave solutions were obtained. Through qualitative methods and the analysis of solitary waveforms, we discovered that in addition to sech-type solitary waves, the system also contains Sech 2 -type solitary waves. By employing the trial functions method, we obtained a single Sech 2 -type solitary wave and verified its existence and stability using the split-Step Fourier Transform method. Furthermore, we use the collision of two Sech 2 -type single solitary waves to excite a stable Sech 2 -type double solitary wave. Similarly, we excite a stable triple solitary wave with three Sech 2 -type single solitary waves. This method can also be used to excite stable multiple solitary waves. It is shown that these solitary wave solutions enrich the dynamic behavior of the KdV-mKdV equation and provide methods for solving Sech 2 -type solitary waves, which hold significant theoretical value.
RESUMEN
BACKGROUND: There are limited clinical data regarding the additional yields of random biopsies (RBs) during colorectal cancer surveillance in patients with inflammatory bowel disease. To assess the additional yield of RB, a systematic review and meta-analysis was conducted. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies investigating the preferred colonoscopy surveillance approach for inflammatory bowel disease patients. The additional yield, detection rate, procedure time, and withdrawal time were pooled. RESULTS: Thirty-seven studies (48 arms) were included in the meta-analysis with 9051 patients. The additional yields of RB were 10.34% in per-patient analysis and 16.20% in per-lesion analysis. The detection rates were 1.31% and 2.82% in per-patient and per-lesion analysis, respectively. Subgroup analysis showed a decline in additional yields from 14.43% to 0.42% in the per-patient analysis and from 19.20% to 5.32% in the per-lesion analysis for studies initiated before and after 2011. In per-patient analysis, the additional yields were 4.83%, 10.29%, and 56.05% for primary sclerosing cholangitis (PSC) proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 0.56%, 1.40%, and 19.45%. In the per-lesion analysis, additional yields were 11.23%, 21.06%, and 45.22% for PSC proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 2.09%, 3.58%, and 16.24%. CONCLUSIONS: The additional yields of RB were 10.34% and 16.20% for per-patient and per-lesion analyses, respectively. Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating RB in the standard colonoscopy surveillance for inflammatory bowel disease patients, especially in those with PSC.