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The kagome metal CsV[Formula: see text]Sb[Formula: see text] is an ideal platform to study the interplay between topology and electron correlation. To understand the fermiology of CsV[Formula: see text]Sb[Formula: see text], intensive quantum oscillation (QO) studies at ambient pressure have been conducted. However, due to the Fermi surface reconstruction by the complicated charge density wave (CDW) order, the QO spectrum is exceedingly complex, hindering a complete understanding of the fermiology. Here, we directly map the Fermi surface of the pristine CsV[Formula: see text]Sb[Formula: see text] by measuring Shubnikov-de Haas QOs up to 29 T under pressure, where the CDW order is completely suppressed. The QO spectrum of the pristine CsV[Formula: see text]Sb[Formula: see text] is significantly simpler than the one in the CDW phase, and the detected oscillation frequencies agree well with our density functional theory calculations. In particular, a frequency as large as 8,200 T is detected. Pressure-dependent QO studies further reveal a weak but noticeable enhancement of the quasiparticle effective masses on approaching the critical pressure where the CDW order disappears, hinting at the presence of quantum fluctuations. Our high-pressure QO results reveal the large, unreconstructed Fermi surface of CsV[Formula: see text]Sb[Formula: see text], paving the way to understanding the parent state of this intriguing metal in which the electrons can be organized into different ordered states.
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MAIN CONCLUSION: MdPRX34L enhanced resistance to Botryosphaeria dothidea by increasing salicylic acid (SA) and abscisic acid (ABA) content as well as the expression of related defense genes. The class III peroxidase (PRX) multigene family is involved in complex biological processes. However, the molecular mechanism of PRXs in the pathogen defense of plants against Botryosphaeria dothidea (B. dothidea) remains unclear. Here, we cloned the PRX gene MdPRX34L, which was identified as a positive regulator of the defense response to B. dothidea, from the apple cultivar 'Royal Gala.' Overexpression of MdPRX34L in apple calli decreased sensitivity to salicylic acid (SA) and abscisic acidï¼ABA). Subsequently, overexpression of MdPRX34L in apple calli increased resistance to B. dothidea infection. In addition, SA contents and the expression levels of genes related to SA synthesis and signaling in apple calli overexpressing MdPRX34L were higher than those in the control after inoculation, suggesting that MdPRX34L enhances resistance to B. dothidea via the SA pathway. Interestingly, infections in apple calli by B. dothidea caused an increase in endogenous levels of ABA followed by induction of ABA-related genes expression. These findings suggest a potential mechanism by which MdPRX34L enhances plant-pathogen defense against B. dothidea by regulating the SA and ABA pathways.
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Ascomicetos , Malus , Malus/metabolismo , Resistencia a la Enfermedad/genética , Ácido Abscísico/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Salicílico/metabolismo , Enfermedades de las Plantas/microbiologíaRESUMEN
Weak light detection is crucial in various practical applications such as night vision systems, flame monitoring, and underwater operations. Decreasing the dark current of a photodetector can effectively mitigate noises, consequently enhancing the signal-to-noise ratio and overall weak light detection performance. Herein, we demonstrate a 4H-SiC UV photodetector capable of detecting extremely weak UV light. This device comprises a photosensitive layer of 4H-SiC, two TiN electrodes and an atomically thin Al2O3 interfacial layer between TiN and the C surface of 4H-SiC. Under 360 nm UV light illumination, the proposed Al2O3 device demonstrates an ultra-low dark current of 18 fA, possibly benefiting from the effective passivation of interfacial carriers, and a boosted photo-to-dark current ratio of 6.7 × 107. Consequently, it achieves a weak-light detection limit as low as 31.8 pW cm-2, significantly outperforming the control device lacking Al2O3. When compared to previously reported SiC photodetectors, our Al2O3 device boasts an exceptional large linear dynamic range of 172 dB. Leveraging this, we construct a photodetector array capable of clearly imaging an object under ultra-weak light illumination below the 100 pW cm-2 level. The proposed photodetector represents a significant advancement in the development of highly sensitive image sensors for weak light detection.
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Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood-brain barrier (BBB). In this study, we prepared a novel core-shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aß11 and Tween 80 (Aß11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aß11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Humanos , Tigeciclina/farmacología , Tigeciclina/uso terapéutico , Minociclina/farmacología , Infecciones por Acinetobacter/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , AguaRESUMEN
The kagome metal CsV3Sb5 features an unusual competition between the charge-density-wave (CDW) order and superconductivity. Evidence for time reversal symmetry breaking (TRSB) inside the CDW phase has been accumulating. Hence, the superconductivity in CsV3Sb5 emerges from a TRSB normal state, potentially resulting in an exotic superconducting state. To reveal the pairing symmetry, we first investigate the effect of nonmagnetic impurity. Our results show that the superconducting critical temperature is insensitive to disorder, pointing to conventional s-wave superconductivity. Moreover, our measurements of the self-field critical current (Ic,sf), which is related to the London penetration depth, also confirm conventional s-wave superconductivity with strong coupling. Finally, we measure Ic,sf where the CDW order is removed by pressure and superconductivity emerges from the pristine normal state. Our results show that s-wave gap symmetry is retained, providing strong evidence for the presence of conventional s-wave superconductivity in CsV3Sb5 irrespective of the presence of the TRSB.
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Cell cycle-dependent kinase 2 (CDK2) is located downstream of CDK4/6 in the cell cycle and regulates cell entry into S-phase by binding to Cyclin E and hyper-phosphorylating Rb. Proto-oncogene murine double minute 2 (MDM2) is a key negative regulator of p53, which is highly expressed in tumors and plays an important role in tumorigenesis and progression. In this study, we identified a dual inhibitor of CDK2 and MDM2, III-13, which had good selectivity for inhibiting CDK2 activity and significantly reduced MDM2 expression. In vitro results showed that III-13 inhibited proliferation of a wide range of tumor cells, regardless of whether Cyclin E1 (CCNE1) was overexpressed or not. The results of in vivo experiments showed that III-13 significantly inhibited proliferation of tumor cells and did not affect body weight of mice. The results of the druggability evaluation showed that III-13 was characterized by low bioavailability and poor membrane permeability when orally administered, suggesting the necessity of further structural modifications. Therefore, this study provided a lead compound for antitumor drugs, especially those against CCNE1-amplified tumor proliferation.
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Antineoplásicos , Neoplasias , Animales , Ratones , Proteína p53 Supresora de Tumor/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Ciclo Celular , Antineoplásicos/farmacología , División CelularRESUMEN
Compound 7-16 was designed and synthesized in our previous study and was identified as a more potential selective 5-HT2A receptor antagonist and inverse agonist for treating Parkinson's disease psychosis (PDP). Then, the metabolism, disposition, and excretion properties of 7-16 and its potential inhibition on transporters were investigated in this study to highlight advancements in the understanding of its therapeutic mechanisms. The results indicate that a total of 10 metabolites of 7-16/[14C]7-16 were identified and determined in five species of liver microsomes and in rats using UPLC-Q Exactive high-resolution mass spectrometry combined with radioanalysis. Metabolites formed in human liver microsomes could be covered by animal species. 7-16 is mainly metabolized through mono-oxidation (M470-2) and N-demethylation (M440), and the CYP3A4 isozyme was responsible for both metabolic reactions. Based on the excretion data in bile and urine, the absorption rate of 7-16 was at least 74.7%. 7-16 had weak inhibition on P-glycoprotein and no effect on the transport activity of OATP1B1, OATP1B3, OAT1, OAT3, and OCT2 transporters. The comprehensive pharmacokinetic properties indicate that 7-16 deserves further development as a new treatment drug for PDP.
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Enfermedad de Parkinson , Agonistas del Receptor de Serotonina 5-HT2 , Antagonistas del Receptor de Serotonina 5-HT2 , Animales , Humanos , Masculino , Ratas , Microsomas Hepáticos/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Agonistas del Receptor de Serotonina 5-HT2/farmacología , Antagonistas del Receptor de Serotonina 5-HT2/farmacología , Metilación , Oxidación-Reducción , Piperidinas/química , Piperidinas/metabolismo , Piperidinas/farmacología , Piridinas/química , Piridinas/metabolismo , Piridinas/farmacologíaRESUMEN
INTRODUCTION: This study was designed to explore the feasibility of semiautomatic measurement of abnormal signal volume (ASV) in glioblastoma (GBM) patients, and the predictive value of ASV evolution for the survival prognosis after chemoradiotherapy (CRT). METHODS: This retrospective trial included 110 consecutive patients with GBM. MRI metrics, including the orthogonal diameter (OD) of the abnormal signal lesions, the pre-radiation enhancement volume (PRRCE), the volume change rate of enhancement (rCE), and fluid attenuated inversion recovery (rFLAIR) before and after CRT were analyzed. Semi-automatic measurements of ASV were done through the Slicer software. RESULTS: In logistic regression analysis, age (HR = 2.185, p = 0.012), PRRCE (HR = 0.373, p < 0.001), post CE volume (HR = 4.261, p = 0.001), rCE1m (HR = 0.519, p = 0.046) were the significant independent predictors of short overall survival (OS) (< 15.43 months). The areas under the receiver operating characteristic curve (AUCs) for predicting short OS with rFLAIR3m and rCE1m were 0.646 and 0.771, respectively. The AUCs of Model 1 (clinical), Model 2 (clinical + conventional MRI), Model 3 (volume parameters), Model 4 (volume parameters + conventional MRI), and Model 5 (clinical + conventional MRI + volume parameters) for predicting short OS were 0.690, 0.723, 0.877, 0.879, 0.898, respectively. CONCLUSION: Semi-automatic measurement of ASV in GBM patients is feasible. The early evolution of ASV after CRT was beneficial in improving the survival evaluation after CRT. The efficacy of rCE1m was better than that of rFLAIR3m in this evaluation.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamiento farmacológico , Quimioradioterapia , Glioblastoma/terapia , Glioblastoma/tratamiento farmacológico , Imagen por Resonancia Magnética , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Polo-like kinase 1 (PLK1) is an attractive therapeutic target for the treatment of tumors, as it is an essential cell-cycle regulator frequently overexpressed in tumor tissues. PLK1 can promote tumor invasion and metastasis, and is often associated with poor prognosis in cancer patients. However, no PLK1 inhibitor has been granted marketing approval until now. Therefore, more potentially promising PLK1 inhibitors need to be investigated. In this study, a series of novel inhibitors targeting PLK1 was designed and optimized derived from a new scaffold. After synthesis and characterization, we obtained the structure-activity relationship and led to the discovery of the most promising compound 30e for PLK1. The antiproliferative activity against HCT116 cells (IC50 = 5 nM versus 45 nM for onvansertib) and the cellular permeability and efflux ratio were significantly improved (PappAâB = 2.03 versus 0.345 and efflux ratio = 1.65 versus 94.7 for 30e and onvansertib, respectively). Further in vivo studies indicated that 30e had favorable antitumor activity with 116.2% tumor growth inhibition (TGI) in comparison with TGI of 43.0% for onvansertib. Furthermore, 30e improved volume of tumor tissue distribution in mice as compared to onvansertib. This initial study on 30e holds promise for further development of an antitumor agent.
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Neoplasias , Inhibidores de Proteínas Quinasas , Animales , Ratones , Inhibidores de Proteínas Quinasas/farmacología , Proteínas de Ciclo Celular , Proteínas Serina-Treonina Quinasas , Línea Celular Tumoral , Proliferación Celular , Quinasa Tipo Polo 1RESUMEN
BACKGROUND: Adenomyosis is a frequent finding in endometrial carcinoma patients. Endometrioid adenocarcinoma is the most common type of endometrial carcinoma; however, endometrioid adenocarcinoma arising from adenomyosis is extremely rare. CASE PRESENTATION: In this case report, we describe a 69-year-old woman who required surgical treatment for pelvic organ prolapse (POP). The patient had been postmenopausal for 20 years and had no abnormal bleeding after menopause. The patient underwent transvaginal hysterectomy, repair of anterior and posterior vaginal walls, ischium fascial fixation and repair of an old perineal laceration. Histological examination of surgical specimens revealed endometrioid adenocarcinoma of the uterus. Bilateral adnexectomy, pelvic lymphadenectomy and para-aortic lymphadenectomy were then performed. The postoperative histopathological diagnosis was stage IB endometrial cancer (endometrioid carcinoma G2). CONCLUSIONS: In summary, endometrioid adenocarcinoma arising from adenomyosis (EC-AIA) is a rare entity and the early diagnosis is difficult. Adequate preoperative assessment and enhanced inquiry of occult clinical symptoms of postmenopausal women before hysterectomy may contribute to the diagnosis of EC-AIA preoperatively.
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Adenomiosis , Carcinoma Endometrioide , Neoplasias Endometriales , Humanos , Femenino , Anciano , Carcinoma Endometrioide/complicaciones , Carcinoma Endometrioide/cirugía , Carcinoma Endometrioide/diagnóstico , Adenomiosis/complicaciones , Adenomiosis/cirugía , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/diagnóstico , Útero , Histerectomía/efectos adversosRESUMEN
BACKGROUND: Gestational trophoblastic neoplasia (GTN) is rare, and it is even rarer for GTN to merge with primary malignant tumors in other organs. Herein is described a rare clinical case of GTN combined with primary lung cancer and mesenchymal tumor of the sigmoid colon, followed with literature review. CASE PRESENTATION: The patient was hospitalized due to diagnosis of GTN with primary lung cancer. Firstly, two cycles of chemotherapy including 5-fluorouracil (5-FU) and actinomycin-D(Act-D) was given. Laparoscopic total hysterectomy and right salpingo-oophorectomy was performed during the third chemotherapy. During the operation, a 3*2 cm nodule was removed which was protruded from the serous surface of the sigmoid colon, and the nodule was confirmed mesenchymal tumor pathologically, in accord with gastrointestinal stromal tumor. During the treatment of GTN, Icotinib tablets were taken orally to control the progression of lung cancer. After 2 cycles of consolidation chemotherapy of GTN, she received thoracoscopic lower lobe of right lung lobectomy and the mediastinum lymph nodes removal. She undertook gastroscopy and colonoscopy and the tubular adenoma of the descending colon was removed. At present, the regular follow-up is taken and she remains free of tumors. CONCLUSIONS: GTN combined with primary malignant tumors in other organs are extremely rare in clinical practice. When imaging examination reveals a mass in other organs, clinicians should be aware of the possibility of a second primary tumor. It will increase the difficulty of GTN staging and treatment. We emphasis the importance of the collaboration of multidisciplinary teams. Clinicians should choose a reasonable treatment plan according to the priorities of different tumors.
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Enfermedad Trofoblástica Gestacional , Neoplasias Pulmonares , Embarazo , Femenino , Humanos , Colon Sigmoide , Estudios Retrospectivos , Enfermedad Trofoblástica Gestacional/diagnóstico , Enfermedad Trofoblástica Gestacional/cirugía , Enfermedad Trofoblástica Gestacional/tratamiento farmacológico , Dactinomicina/uso terapéuticoRESUMEN
Ovarian cancer (OC) is one of the most prevalent malignant tumors affecting women's life and health. Since OC has a poor prognosis due to extensive metastasis, there is a need to explore a new mechanism of OC metastasis. microRNAs (miRs) are single-stranded, non-coding RNAs. miR-9 has been reported to promote cancer and may provide a new strategy for OC diagnosis. The purpose of this study was to examine the function and underlying mechanism of miR-9 in OC. RT-qPCR was used to assess miR-9 expression levels. Transwell assays were used to determine the number of migrating and invading OC cells. The protein expression levels of the PI3K/AKT/mTOR/GSK3ß signaling pathway were examined using western blotting. The results informed that, when compared to normal ovarian tissues, miR-9 was remarkably expressed in OC tissues, and hypoxia might lead to overexpression of miR-9-5p while inhibiting miR-9 notably suppressed the migrating and invading cell numbers in OC cells. In vivo, miR-9-5p knockdown inhibited tumor growth in a subcutaneous nude mice model of SKOV3 cells. Our findings suggest that miR-9 could be an underlying oncogene in OC, opening up new avenues for OC diagnosis and treatment of OC by targeting miR-9.
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MicroARNs , Neoplasias Ováricas , Humanos , Animales , Ratones , Femenino , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones Desnudos , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proliferación Celular , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Ováricas/patología , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Línea Celular Tumoral , Movimiento CelularRESUMEN
BACKGROUND: Brain microvascular endothelial cell (BMEC) functions loss is a key event in the development of ischemic stroke, which may be affected by the dysregulation of circular RNAs (circRNAs). We aimed to unveil the role of circRNA FKBP Prolyl Isomerase 3 (circFKBP3) in cell models of ischemic stroke. METHODS: Cell models of ischemic stroke were constructed in human BEMCs (HBMECs) with the treatment of oxygen glucose deprivation (OGD). Quantitative real-time PCR (qPCR) and western blotting were conducted for expression analysis of circFKBP3, miR-766-3p and TNF receptor associated factor 3 (TRAF3). CCK-8, transwell, wound healing, flow cytometry, tube formation and ELISA assays were implemented to monitor cell viability, migration, apoptosis, angiogenesis and inflammation production. The putative binding relationship between miR-766-3p and circFKBP3 or TRAF3 was validated by dual-luciferase, RIP and pull-down assays. RESULTS: CircFKBP3 expression was elevated in OGD-treated HBMECs. OGD suppressed HBMEC viability, migration, angiogenesis, and provoked cell apoptosis and inflammation production, while knockdown of circFKBP3 attenuated these effects. CircFKBP3 interacted with miR-766-3p, and circFKBP3 absence-repressed HBMEC function loss and inflammation were recovered by miR-766-3p inhibition. CircFKBP3 targeted miR-766-3p to regulate TRAF3 expression. MiR-766-3p enrichment-repressed HBMEC function loss and inflammation were recovered by TRAF3 overexpression. CONCLUSION: CircFKBP3 absence alleviated OGD-induced function loss and inflammatory responses of HBMECs via governing the miR-766-3p/TRAF3 axis.
CircFKBP3 expression is elevated in OGD-treated HBMECs.OGD-induced HBMEC function loss and inflammation are alleviated by circFKBP3 absence.CircFKBP3 directly targets miR-766-3p to regulate TRAF3 expression.
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Given the advantage of LoRaWAN private networks, multiple types of services have been implemented by users in one LoRaWAN system to realize various smart applications. With an increasing number of applications, LoRaWAN suffers from multi-service coexistence challenges due to limited channel resources, uncoordinated network configuration, and scalability issues. The most effective solution is establishing a reasonable resource allocation scheme. However, existing approaches are not applicable for LoRaWAN with multiple services with different criticalities. Therefore, we propose a priority-based resource allocation (PB-RA) scheme to coordinate multi-service networks. In this paper, LoRaWAN application services are classified into three main categories, including safety, control, and monitoring. Considering the different criticalities of these services, the proposed PB-RA scheme assigns spreading factors (SFs) to end devices on the basis of the highest priority parameter, which decreases the average packet loss rate (PLR) and improves throughput. Moreover, a harmonization index, namely HDex, based on IEEE 2668 standard is first defined to comprehensively and quantitively evaluate the coordination ability in terms of key quality of service (QoS) performance (i.e., PLR, latency and throughput). Furthermore, Genetic Algorithm (GA)-based optimization is formulated to obtain the optimal service criticality parameters which maximize the average HDex of the network and contribute to a larger capacity of end devices while maintaining the HDex threshold for each service. Simulations and experimental results show that the proposed PB-RA scheme can achieve the HDex score of 3 for each service type at 150 end devices, which improves the capacity by 50% compared to the conventional adaptive data rate (ADR) scheme.
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BACKGROUND: Group 2 innate lymphoid cells (ILC2s), the innate counterpart of TH2 cells, play a critical role in type 2 immune responses. However, the molecular regulatory mechanisms of ILC2s are still unclear. OBJECTIVE: The aim of this study was to explore the importance of signal transducer and activator of transcription 3 (STAT3) to ILC2 function in allergic lung inflammation. METHODS: Acute and chronic asthma models were established by intranasal administration of the protease allergen papain in VavicreStat3fl/fl, Il5tdtomato-creStat3fl/fl, and RorccreStat3fl/fl mice to verify the necessity of functional STAT3 for ILC2 allergic response. The intrinsic role of STAT3 in regulating ILC2 function was examined by generation of bone marrow chimera mice. The underlying mechanism was studied through confocal imaging, metabolomics analysis, and chromatin immunoprecipitation quantitative PCR. RESULTS: STAT3 is essential for ILC2 effector function and promotes ILC2-driven allergic inflammation in the lung. Mechanistically, the alarmin cytokine IL-33 induces a noncanonical STAT3 phosphorylation at serine 727 in ILC2s, leading to translocation of STAT3 into the mitochondria. Mitochondrial STAT3 further facilitates adenosine triphosphate synthesis to fuel the methionine cycle and generation of S-adenosylmethionine, which supports the epigenetic reprogramming of type 2 cytokines in ILC2s. STAT3 deficiency, inhibition of STAT3 mitochondrial translocation, or blockade of methionine metabolism markedly dampened the ILC2 allergic response and ameliorated allergic lung inflammation. CONCLUSION: The mitochondrial STAT3-methionine metabolism pathway is a key regulator that shapes ILC2 effector function through epigenetic regulation, and the related proteins or metabolites represent potential therapeutic targets for allergic lung inflammation.
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Alveolitis Alérgica Extrínseca , Hipersensibilidad , Neumonía , Eosinofilia Pulmonar , Animales , Citocinas , Epigénesis Genética , Inmunidad Innata , Interleucina-33 , Pulmón , Linfocitos , Metionina , Ratones , Mitocondrias , Factor de Transcripción STAT3RESUMEN
PLK-1 (Polo-like kinase-1) plays an essential role in cytokinesis, and its aberrant expression is considered to be keenly associated with a wide range of cancers. It has been selected as an appealing target and small-molecule inhibitors have been developed and studied in clinical trials. Unfortunately, most have been declared as failures due to the poor therapeutic response and off-target toxicity. In the present study, a novel potent PLK-1 inhibitor, compound 7a, was designed and synthetized. 1H NMR, 13C NMR, 19F NMR and mass spectrum were comprehensively used for the compound characterization. The compound exhibited higher potency against PLK-1 kinase, HCT-116 and NCI-H2030 cell lines than the positive control. Molecular docking indicated that the binding mode that the ATP binding site of PLK-1 was occupied by the compound. Then, a UHPLC-MS/MS method was established and validated to explore the pharmacokinetic behavior of the drug candidate. The method had good selectivity, high sensitivity and wide linearity. The exposure increased linearly with the dose, but the oral bioavailability was not satisfactory enough. Then, the metabolism was studied using liver microsomes by UHPLC-Q-Orbitrap/HRMS. Our research first studied the pharmacokinetic metabolic characteristics of 7a and may serve as a novel lead compound for the development of PLK-1 inhibitors.
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Metaboloma , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Simulación del Acoplamiento Molecular , Disponibilidad BiológicaRESUMEN
The apoplast serves as the first battlefield between the plant hosts and invading microbes; therefore, work on plant-pathogen interactions has increasingly focused on apoplastic immunity. In this study, we identified three proteins in the apoplast of cotton (Gossypium sp) root cells during interaction of the plant with the fungal pathogen Verticillium dahliae Among these proteins, cotton host cells secrete chitinase 28 (Chi28) and the Cys-rich repeat protein 1 (CRR1), while the pathogen releases the protease VdSSEP1. Biochemical analysis demonstrated that VdSSEP1 hydrolyzed Chi28, but CRR1 protected Chi28 from cleavage by Verticillium dahliae secretory Ser protease 1 (VdSSEP1). In accordance with the in vitro results, CRR1 interacted with Chi28 in yeast and plant cells and attenuated the observed decrease in Chi28 level that occurred in the apoplast of plant cells upon pathogen attack. Knockdown of CRR1 or Chi28 in cotton plants resulted in higher susceptibility to V. dahliae infection, and overexpression of CRR1 increased plant resistance to V dahliae, the fungus Botrytis cinerea, and the oomycete Phytophthora parasitica var nicotianae By contrast, knockout of VdSSEP1 in V. dahliae destroyed the pathogenicity of this fungus. Together, our results provide compelling evidence for a multilayered interplay of factors in cotton apoplastic immunity.
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Quitinasas/metabolismo , Gossypium/metabolismo , Gossypium/microbiología , Proteínas de Plantas/metabolismo , Verticillium/patogenicidad , Quitinasas/genética , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Gossypium/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/genéticaRESUMEN
Conjugated polymers feature promising structure and properties for photocatalytic water splitting. Herein, a hydrolysis strategy was demonstrated to rationally modulate the surface hydrophilicity and band structures of conjugated poly-benzothiadiazoles. High hydrophilicity not only enhances the dispersions of polymeric solids in an aqueous solution but also reduces the absorption energy of water molecules. Besides, both theoretical and experimental results reveal that a more positive valence band potential is generated, which contributes to enhancing the photocatalytic water oxidation performance. Accordingly, the surface-modified conjugated polymers show largely promoted photocatalytic water oxidation activities by deposition of cobalt oxides as cocatalysts.
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Sugars are essential regulatory molecules involved in plant growth and development and defense response. Although the relationship between sugars and disease resistance has been widely discussed, the underlying molecular mechanisms remain unexplored. Ring rot caused by Botryosphaeria dothidea (B. dothidea), which severely affects fruit quality and yield, is a destructive disease of apples (Malus domestica Borkh.). The present study found that the degree of disease resistance in apple fruit was closely related to glucose content. Therefore, the gene encoding a hexokinase, MdHXK1, was isolated from the apple cultivar 'Gala', and characterized during the defense response. Overexpression of MdHXK1 enhanced disease resistance in apple calli, leaves and fruits by increasing the expression levels of genes related to salicylate (SA) synthesis (PHYTOALEXIN DEFICIENT 4, PAD4; PHENYLALANINE AMMONIA-LYASE, PAL; and ENHANCED DISEASE SUSCEPTIBILITY 1, EDS1) and signaling (PR1; PR5; and NONEXPRESSER OF PR GENES 1, NPR1) as well as increasing the superoxide (O2- ) production rate and the hydrogen peroxide (H2 O2 ) content. Overall, the study provides new insights into the MdHXK1-mediated molecular mechanisms by which glucose signaling regulates apple ring rot resistance.
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Ascomicetos , Malus , Ascomicetos/fisiología , Resistencia a la Enfermedad/genética , Glucosa/metabolismo , Malus/genética , Malus/metabolismo , Enfermedades de las Plantas/genéticaRESUMEN
To solve the issue of polymeric materials recycling, developing intrinsic self-healing materials containing dynamic bonds has attracted many researchers' highly concerning. However, the tradeoff between their mechanical strength and stretchability always does not avoid. Herein, to surmount the above tradeoff, metal-ligand (Cu2+ -S) interactions are introduced into the cross-linking polythiourethane covalent adaptable networks (PTU CANs) with three kinds of dynamic motifs (thiourethane, disulfide, and hydrogen bonds). When the molar ratio of Cu2+ to S is 6.37%, the break strength (9.41 ± 0.34 MPa) and Young's modulus (26.02 ± 0.55 MPa) of the metal-ligand coordination complex PTU (Cu2+ -PTU-3) dramatically increase, whereas the peak strain almost does not decline (454.44 ± 3.95%). To conduct the repairing, Cu2+ -PTU-3 is further confirmed excellent repairing capability. Therefore, these new PTU CANs have significant potential for the new self-healing materials.