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Ammonia (NH3) is pivotal to the fertilizer industry and one of the most commonly produced chemicals1. The direct use of atmospheric nitrogen (N2) had been challenging, owing to its large bond energy (945 kilojoules per mole)2,3, until the development of the Haber-Bosch process. Subsequently, many strategies have been explored to reduce the activation barrier of the N≡N bond and make the process more efficient. These include using alkali and alkaline earth metal oxides as promoters to boost the performance of traditional iron- and ruthenium-based catalysts4-6 via electron transfer from the promoters to the antibonding bonds of N2 through transition metals7,8. An electride support further lowers the activation barrier because its low work function and high electron density enhance electron transfer to transition metals9,10. This strategy has facilitated ammonia synthesis from N2 dissociation11 and enabled catalytic operation under mild conditions; however, it requires the use of ruthenium, which is expensive. Alternatively, it has been shown that nitrides containing surface nitrogen vacancies can activate N2 (refs. 12-15). Here we report that nickel-loaded lanthanum nitride (LaN) enables stable and highly efficient ammonia synthesis, owing to a dual-site mechanism that avoids commonly encountered scaling relations. Kinetic and isotope-labelling experiments, as well as density functional theory calculations, confirm that nitrogen vacancies are generated on LaN with low formation energy, and efficiently bind and activate N2. In addition, the nickel metal loaded onto the nitride dissociates H2. The use of distinct sites for activating the two reactants, and the synergy between them, results in the nickel-loaded LaN catalyst exhibiting an activity that far exceeds that of more conventional cobalt- and nickel-based catalysts, and that is comparable to that of ruthenium-based catalysts. Our results illustrate the potential of using vacancy sites in reaction cycles, and introduce a design concept for catalysts for ammonia synthesis, using naturally abundant elements.
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Chaihu Shugan San (CSS) is a well-known traditional herbal formula that has the potential to ameliorate hepatocellular carcinoma (HCC); however, its mechanism of action remains unknown. Here, we identified the key targets of CSS against HCC and developed a prognostic model to predict the survival of patients with HCC. The effect of CSS plus sorafenib on HCC cell proliferation was evaluated using the MTT assay. LASSO-Cox regression was used to establish a three-gene signature model targeting CSS. Correlations between immune cells, immune checkpoints and risk score were determined to evaluate the immune-related effects of CSS. The interactions between the components and targets were validated using molecular docking and Surface Plasmon Resonance (SPR) assays. CSS and sorafenib synergistically inhibited HCC cell proliferation. Ten core compounds and 224 targets were identified using a drug compound-target network. The prognostic model of the three CSS targets (AKT1, MAPK3 and CASP3) showed predictive ability. Risk scores positively correlated with cancer-promoting immune cells and high expression of immune checkpoint proteins. Molecular docking and SPR analyses confirmed the strong binding affinities of the active components and the target genes. Western blot analysis confirmed the synergistic effect of CSS and sorafenib in inhibiting the expression of these three targets. In conclusion, CSS may regulate the activity of immune-related factors in the tumour microenvironment, reverse immune escape, enhance immune responses through AKT1, MAPK3, and CASP3, and synergistically alleviate HCC. The co-administration of sorafenib with CSS has a strong clinical outlook against HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Sorafenib/farmacología , Caspasa 3 , Simulación del Acoplamiento Molecular , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Microambiente TumoralRESUMEN
2D heterostructuring is a versatile methodology for designing nanoarchitecture catalytic systems that allow for reconstruction and modulation of interfaces and electronic structures. However, catalysts with such structures are extremely scarce due to limited synthetic strategies. Here, a highly ordered 2D Ru/Si/Ru/Si nano-heterostructures (RSHS) is reported by acid etching of the LaRuSi electride. RSHS shows a superior electrocatalytic activity for hydrogen evolution with an overpotential of 14 mV at 10 mA cm-2 in alkaline media. Both experimental analysis and first-principles calculations demonstrate that the electronic states of Ru can be tuned by strong interactions of the interfacial Ru-Si, leading to an optimized hydrogen adsorption energy. Moreover, due to the synergistic effect of Ru and Si, the energy barrier of water dissociation is significantly reduced. The well-organized superlattice structure will provide a paradigm for construction of efficient catalysts with tunable electronic states and dual active sites.
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PURPOSE: To analyze the characteristics of cerebral blood flow changes of poor sleep quality in people with epilepsy(PWE). METHODS: 90 PWE treated in The General Hospital of Ningxia Medical University from December 2021 to September 2023 were divided into poor sleep quality group (PSQG) and good sleep quality group (GSQG) according to the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), to compare the differences in cerebral perfusion between the two groups of patients, so as to summarize the characteristics of cerebral blood flow changes of poor sleep quality in PWE. RESULTS: The positive rate of interictal single-photon emission computed tomography/computed tomography (SPECT/CT) was 76.7 %(69/90), which showed localized cerebral hypoperfusion. There was no statistical difference between the two groups of PSQG (N=29) and GSQG (N=61) in terms of the positive rate of SPECT/CT, the number of hypoperfusion foci, and the range of hypoperfusion foci. In PSQG and GSQG, 9 patients(31.0 %) and 6 patients(9.8 %) showed hypoperfusion in the right parietal lobe, respectively, and the difference between the two groups was statistically significant (P=0.017). There was no statistical difference the rate of the interictal epileptiform discharges (IEDs) and the brain area of IEDs in electroencephalography(EEG) between the two groups. CONCLUSION: SPECT/CT of poor sleep quality in PWE demonstrated hypoperfusion in the right parietal lobe.
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BACKGROUND AND OBJECTIVES: The prognosis of patients with spontaneous intracerebral hemorrhage (ICH) is often influenced by hematoma volume, a well-established predictor of poor outcome. However, the optimal intraventricular hemorrhage (IVH) volume cutoff for predicting poor outcome remains unknown. METHODS: We analyzed 313 patients with spontaneous ICH not undergoing evacuation, including 7 cases with external ventricular drainage (EVD). These patients underwent a baseline CT scan, followed by a 24-hour CT scan for measurement of both hematoma and IVH volume. We defined hematoma growth as hematoma growth > 33 % or 6 mL at follow-up CT, and poor outcome as modified Rankin Scale score≥3 at three months. Cutoffs with optimal sensitivity and specificity for predicting poor outcome were identified using receiver operating curves. RESULTS: The receiver operating characteristic analysis identified 6 mL as the optimal cutoff for predicting poor outcome. IVH volume> 6 mL was observed in 53 (16.9 %) of 313 patients. Patients with IVH volume>6 mL were more likely to be older and had higher NIHSS score and lower GCS score than those without. IVH volume>6 mL (adjusted OR 2.43, 95 % CI 1.13-5.30; P = 0.026) was found to be an independent predictor of poor clinical outcome at three months in multivariable regression analysis. CONCLUSIONS: Optimal IVH volume cutoff represents a powerful tool for improving the prediction of poor outcome in patients with ICH, particularly in the absence of clot evacuation or common use of EVD. Small amounts of intraventricular blood are not independently associated with poor outcome in patients with intracerebral hemorrhage. The utilization of optimal IVH volume cutoffs may improve the clinical trial design by targeting ICH patients that will obtain maximal benefit from therapies.
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Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Hemorragia Cerebral Intraventricular/diagnóstico por imagen , Hemorragia Cerebral Intraventricular/fisiopatología , Hemorragia Cerebral Intraventricular/terapia , Hemorragia Cerebral Intraventricular/diagnóstico , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/terapia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/fisiopatología , Factores de Riesgo , Factores de Tiempo , Anciano de 80 o más Años , Evaluación de la Discapacidad , Hematoma/diagnóstico por imagen , Hematoma/diagnóstico , Curva ROCRESUMEN
Objective: To explore the effects of clinical nursing pathway (CNP) on the postoperative satisfaction and quality of life (QOL) of patients with subarachnoid hemorrhage (SAH). Methods: This is a retrospective study. Eighty patients with SAH admitted to Baoding No.1 Central Hospital from June 2021 to January 2023 were prospectively divided into a observation group and a control group by random numbers. The control group was given routine nursing, and the observation group was additional given CNP. The prognosis, cognitive function, QOL, self-care ability, nursing satisfaction and the incidence of complications were compared between the two groups. Results: After CNP nursing, the GCS and MMSE scores in the observation group were higher than those in the control group 14 days, one month and six months after the operation; and the difference was statistically significant (p< 0.05). Six months after the operation, the SS-QOL and Ability of daily living (ADL) scores in both groups were significantly improved compared with those before the intervention; and the improvement in the observation group was significantly better than that in the control group; and the difference was statistically significant(p<0.05). The nursing satisfaction score in the observation group was significantly higher than in the control group. The total incidence of complications in the observation group was lower than that in the control group. Conclusions: The CNP intervention in perioperative period of SAH patients has remarkable clinical effect, can improve the pertinence and efficiency of nursing, promote patients to recover as soon as possible, significantly improve the QOL of patients,and is worthy of clinical popularization.
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OBJECTIVES: To estimate adolescents and children age using stepwise regression and machine learning methods based on the pulp and tooth volumes of the left maxillary central incisor and cuspid on cone beam computed tomography (CBCT) images, and to compare and analyze the estimation results. METHODS: A total of 498 Shanghai Han adolescents and children CBCT images of the oral and maxillofacial regions were collected. The pulp and tooth volumes of the left maxillary central incisor and cuspid were measured and calculated. Three machine learning algorithms (K-nearest neighbor, ridge regression, and decision tree) and stepwise regression were used to establish four age estimation models. The coefficient of determination, mean error, root mean square error, mean square error and mean absolute error were computed and compared. A correlation heatmap was drawn to visualize and the monotonic relationship between parameters was visually analyzed. RESULTS: The K-nearest neighbor model (R2=0.779) and the ridge regression model (R2=0.729) outperformed stepwise regression (R2=0.617), while the decision tree model (R2=0.494) showed poor fitting. The correlation heatmap demonstrated a monotonically negative correlation between age and the parameters including pulp volume, the ratio of pulp volume to hard tissue volume, and the ratio of pulp volume to tooth volume. CONCLUSIONS: Pulp volume and pulp volume proportion are closely related to age. The application of CBCT-based machine learning methods can provide more accurate age estimation results, which lays a foundation for further CBCT-based deep learning dental age estimation research.
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Determinación de la Edad por los Dientes , Tomografía Computarizada de Haz Cónico , Pulpa Dental , Aprendizaje Automático , Humanos , Tomografía Computarizada de Haz Cónico/métodos , Adolescente , Niño , Determinación de la Edad por los Dientes/métodos , Pulpa Dental/diagnóstico por imagen , Diente/diagnóstico por imagen , China , Incisivo/diagnóstico por imagen , Incisivo/anatomía & histología , Femenino , Masculino , AlgoritmosRESUMEN
The water (H2 O) dissociation is critical for various H2 O-associated reactions, including water gas shift, hydrogen evolution reaction and hydrolysis corrosion. While the d-band center concept offers a catalyst design guideline for H2 O activation, it cannot be applied to intermetallic or main group elements-based systems because Coulomb interaction was not considered. Herein, using hydrolysis corrosion of Mg as an example, we illustrate the critical role of the dipole of the intermetallic catalysts for H2 O dissociation. The H2 O dissociation kinetics can be enhanced using Mgx Mey (Me=Co, Ni, Cu, Si and Al) as catalysts, and the hydrogen generation rate of Mg2 Ni-loaded Mg reached 80â times as high as Ni-loaded Mg. The adsorbed H2 O molecules strongly couple with the Mg-Me dipole of Mgx Mey , lowering the H2 O dissociation barrier. The dipole-based H2 O dissociation mechanism is applicable to non-transition metal-based systems, such as Mg2 Si and Mg17 Al12 , offering a flexible catalyst design strategy for controllable H2 O dissociation.
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PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.
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Adenosina Desaminasa , Péptidos y Proteínas de Señalización Intercelular , Humanos , Adenosina Desaminasa/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Estudios de Cohortes , Estudios Retrospectivos , MutaciónRESUMEN
Poor carrier transport capacity and numerous surface defects of charge transporting layers (CTLs), coupled with misalignment of energy levels between perovskites and CTLs, impact photoelectric conversion efficiency (PCE) of inverted perovskite solar cells (PSCs) profoundly. Herein, a collaborative passivation strategy is proposed based on 4-(chloromethyl) benzonitrile (CBN) as a solution additive for fabrication of both [6,6]-phenyl-C61-butyric acid methylester (PCBM) and poly(triarylamine) (PTAA) CTLs. This additive can improve wettability of PTAA and reduce the agglomeration of PCBM particles, which enhance the PCE and device stability of the PSCs. As a result, a PCE exceeding 20% with a remarkable short circuit current of 23.9 mA cm-2 , and an improved fill factor of 81% is obtained for the CBN- modified inverted PSCs. Devices maintain 80% and 70% of the initial PCE after storage under 30% and 85% humidity ambient conditions for 1000 h without encapsulation, as well as negligible light state PCE loss. This strategy demonstrates feasibility of the additive engineering to improve interfacial contact between the CTLs and perovskites for fabrication of efficient and stable inverted PSCs.
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BACKGROUND: Glioblastoma (GBM) is the most malignant glioma, with poor survival rates and prognosis. Several studies have reported the abnormal expression of circular RNAs (circRNAs) and their functions in the malignant biological behavior of GBM. However, such research is still in the preliminary stages, and further study is needed to confirm the therapeutic potential of circRNAs in GBM. METHODS: RNA-seq was performed using four tumor tissues from patients with GBM and their adjacent non-tumor brain tissues to screen differentially expressed circRNAs. Fluorescence in situ hybridization assay was used to examine the location of circ_0021350 in glioma cells. In addition, a series of biological function assays were employed to verify the oncogenic role of circ_0021350 in GBM. Quantitative reverse transcription PCR was used to examine circular, micro- (miRNA), and messenger RNA (mRNA) levels. Furthermore, dual-luciferase reporter, RNA pull-down, and RNA binding protein immunoprecipitation assays were applied to verify the interaction between circ_0021350 and its downstream effectors. RESULTS: Circ_0021350 was significantly elevated in GBM tissues and glioma cells. Overexpression of circ_0021350 promoted glioma cell proliferation and metastatic ability; silencing of circ_0021350 had the opposite effect. Mechanistic analysis revealed that circ_0021350 sponged miR-1207-3p to regulate PIK3R3, whose overexpression reversed the reduction in the malignant biological behavior of glioma cells caused by silencing circ_0021350. CONCLUSION: Our findings suggest that circ_0021350 is an oncogenic circRNA in GBM, and the circ_0021350/miR-1207-3p/PIK3R3 axis may serve as a potential therapeutic target in GBM treatment.
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Glioblastoma , Glioma , MicroARNs , Humanos , Glioblastoma/genética , Hibridación Fluorescente in Situ , ARN Circular/genética , Oncogenes , MicroARNs/genética , Fosfatidilinositol 3-QuinasasRESUMEN
Objective: To evaluate the effect of nimodipine combined with atorvastatin calcium on the micro inflammation and oxidative stress levels in patients with cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) and its clinical implications. Methods: A total of 80 patients with CVS caused by SAH who had been admitted to Baoding First Central Hospital from August 2021 to August 2022 were selected and randomly divided into two groups. The control group underwent conventional symptomatic treatment, while the experimental group was administered nimodipine combined with atorvastatin calcium on the basis of conventional treatment. The changes in the micro inflammatory cytokines and oxidative stress factors in the two groups were compared, as well as the differences in clinical efficacy and incidence of adverse drug reactions. Result: After treatment, the levels of inflammatory cytokines in the experimental group decreased more significantly than those in the control group (p=0.00). After treatment, the serum levels of oxidative stress factors were obviously higher in the experimental group than in the control group (p=0.00). After treatment, the total efficacy was 77.5% in the experimental group and 55% in the control group, and the difference was statistically significant (p=0.04). Conclusions: Nimodipine combined with atorvastatin calcium could significantly improve the clinical symptoms in patients with CVS after SAH, which would be beneficial, safe, and effective for the patient's recovery.
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Objective: To investigate the effect of butylphthalide combined with fasudil in the treatment of subarachnoid hemorrhage (SAH) with cerebral vasospasm (CVS) on inflammatory factors, cognitive function and vascular endothelial function. Methods: It is a retrospective study in which a total of 104 patients with SAH with CVS admitted to Baoding First Central Hospital from July 2020 to February 2022 were selected and randomly divided into two groups by drawing lots. Patients in the control group were treated with basic symptomatic treatment, while those in the observation group were treated with butylphthalide soft capsule combined with fasudil hydrochloride injection on the basis of the control group. Before and after treatment, serum neuron specific enolase (NSE), tumor necrosis factor-α(TNF-α), interleukin-8(IL-8), hypersensitive C-reactive protein (CRP), Birmingham Cognitive Screen test (BCoS) score, serum soluble intercellular adhesion molecule-1(ICAM-1), serum endothelin-1(ET-1), vascular endothelial growth factor (VEGF) levels, and endothelium-dependent vasodilation function (FMD) in the two groups were compared. Results: After treatment, the expression levels of NSE, TNF-α, IL-8 and CRP in the two groups were significantly decreased, and the expression levels of all indicators in the observation group were lower than that in the control group (p<0.05). After treatment, the scores of orientations, attention, memory, language, practice and action in the two groups were significantly increased, and the scores of all dimensions in the observation group were higher than those in the control group (p<0.05). After treatment, S-ICAM-1, ET-1, VEGF, FMD decreased in both groups, and all indicators of the observation group were lower than those of the control group, with statistically significant differences (p<0.05). Conclusion: Butylphthalide combined with fasudil therapy was found as effective in reducing inflammatory factors, ameliorating cognitive function and vascular endothelial function in patients with subarachnoid hemorrhage complicated with cerebral vasospasm.
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Constructing hierarchical micro/nanostructures as anodes for sodium ion batteries is an important approach for exploiting efficient energy storage devices. Herein, sandwich structure hierarchical nanofibers composed of hollow carbon fibers as the substrate, and MoS2 as the interlayer with Co and/or ZnS nanoparticles anchoring in carbon skeletons as the outer shell (carbon nanofiber/MoS2 /Co-ZnSâNC) are prepared via a multistep reaction strategy. Profiting from the unique hierarchical structure, abundant migration channels of Na+ , and multicomponent synergistic effects, the rapid diffusion kinetics are ensured and the utilization of active materials is maximized. The coaxial structure can evenly disperse volumetric strain, making structural stability guaranteed. Hierarchical nanofibers deliver a high reversible capacity of 352.3 mAh g-1 at 5.0 A g-1 over 3000 cycles. A discharge capacity of 182.5 mAh g-1 is retained even after 10 000 cycles at 10.0 A g-1 as well as a high rate capacity of 202.0 mAh g-1 up to 30 A g-1 . The optimal atomic ratio of Co element is further verified by the kinetic analysis. The full-cells assembled with Na3 V2 (PO4 )3 cathode provide a high capacity of 179.2 mAh g-1 at 1.0 A g-1 for 500 cycles. Combining in situ and ex situ characterizations and theoretical calculations, possible sodium storage mechanisms and the origin of superior electrochemical properties are revealed.
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Inorganic electrides have been proved to be efficient hosts for incorporating transition metals, which can effectively act as active sites giving an outstanding catalytic performance. Here, it is demonstrated that a reusable and recyclable (for more than 7 times) copper-based intermetallic electride catalyst (LaCu0.67 Si1.33 ), in which the Cu sites activated by anionic electrons with low-work function are uniformly dispersed in the lattice framework, shows vast potential for the selective C-H oxidation of industrially important hydrocarbons and cycloaddition of CO2 with epoxide. This leads to the production of value-added cyclic carbonates under mild reaction conditions. Importantly, the LaCu0.67 Si1.33 catalyst enables much higher turnover frequencies for the C-H oxidation (up to 25 276 h-1 ) and cycloaddition of CO2 into epoxide (up to 800 000 h-1 ), thus exceeding most nonnoble as well as noble metal catalysts. Density functional theory investigations have revealed that the LaCu0.67 Si1.33 catalyst is involved in the conversion of N-hydroxyphthalimide (NHPI) into the phthalimido-N-oxyl (PINO), which then triggers selective abstraction of an H atom from ethylbenzene for the generation of a radical susceptible to further oxygenation in the presence of O2 .
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HMGA1 has been reported to be aberrantly expressed and correlate with the poor prognosis of many carcinomas. This study aimed to investigate the clinical significance and molecular mechanism of HMGA1 as a tumor-suppressing gene in hepatocellular carcinoma (HCC). Analysis of TCGA dataset by TANRIC website and R2 platform, we found that HMGA1 expression was significantly higher in HCC tissues compared to that in normal liver tissues and was associated with Edmondson grade. Patients with highly expressed HMGA1 had worse overall survival. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis showed the potential relationships between HMGA1 and other genes in HCC. We also demonstrated that the downregulation of HMGA1 dramatically suppressed the proliferation and migration of HCC cells. Furthermore, ectopic expression of HMGA1 blocked G0/G1 to S transition. Subsequent investigation characterized HMGA1 as a direct target of miR-195-5p, and miR-195-5p downregulation abrogated the effect of HMGA1 on HCC proliferation, migration, and cell cycle arrest. In addition, we also demonstrated that miR-195-5p downregulation abrogated the effect of HMGA1 on HCC growth in vivo. Taken together, our data provide strong evidence that HMGA1 promotes HCC and is negatively regulated by the tumor-suppressor, miR-195-5p.
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Carcinoma Hepatocelular/genética , Proteína HMGA1a/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , Animales , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Ontología de Genes , Genes Supresores de Tumor , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Clasificación del Tumor , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The Chinese medicinal herb Mahuang is herbaceous stem of Ephedra sinica, E. intermedia, or E. equisetina(Family, Ephedraceae). In China, Mahuang has been used, all the way over a millennium, as a key component herb of many herbal medicines for management of epidemics of acute respiratory illness and is also used in officially recommended herbal medicines for COVID-19. Mahuang is the first-line medicinal herb for cold and wheezing and also an effective diuretic herb for edema. However, Mahuang can also exert significant adverse effects. The key to safety and effectiveness is rational and precise use of the herb. In this review article, we comprehensively summarize chemical composition of Mahuang and associated differences in pharmacognosy, pharmacodynamics and pharmacokinetics of Mahuang compounds, along with the adverse effects of Mahuang compounds and products. Based on full understanding of how Mahuang is used in Chinese traditional medicine, systematic research on Mahuang in line with contemporary standards of pharmaceutical sciences will facilitate promoting Chinese herbal medicines to become more efficient in management of epidemic illnesses, such as COVID-19. To this end, we recommend research on Mahuang of two aspects, i.e., pharmacological investigation for its multicompound-involved therapeutic effects and toxicological investigation for clinical manifestation of the adverse effects, chemicals responsible for the adverse effects, and conditions for safe use of the herb and the herb-containing medicines.
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Tratamiento Farmacológico de COVID-19 , Medicamentos Herbarios Chinos , Ephedra sinica , Ephedra , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Ephedra sinica/química , Efedrina/química , Humanos , PlantasRESUMEN
This study aimed to explore the protective effect of Reduning Injection(RDN) on mice infected by influenza virus A/PR/8(PR8) and its immune regulatory roles during viral infection. In in vivo experiments, female C57 BL/6 mice were randomly divided into phosphate buffered saline(PBS) group, PR8-infected group, oseltamivir treatment group(OSV) and RDN treatment group. After 2 h of PR8 infection, mice in the oseltamivir group were gavaged with oseltamivir 30 mg·kg~(-1), and those in the RDN treatment group were injected intraperitoneally with RDN 1.5 mL·kg~(-1)once per day for seven consecutive days. The body weight of mice in each group was recorded at the same time every morning for 16 consecutive days. The line chart of body weight change was created to analyze the protective effect of RDN on flu-infected mice. The relative mRNA expression of different cytokines(IL-6, TNF-α, MCP-1, IL-1ß, MIP-2, IP-10 and IL-10) in lung samples of flu-infected mice was detected by PCR. Flow cytometry was utilized to analyze the composition of immune cells of mouse BALF samples on day 5 after infection. Mouse macrophage cell line RAW264.7 was planted and treated by different concentrations of RDN(150, 300, 600 µg·mL~(-1)) for 24 h or 48 h, and cell proliferation was detected by CCK-8 assay. RAW264.7 cells and mouse primary peritoneal macrophages were stimulated with synthetic single stranded RNA(R837), which elicited the inflammatory response by mimicking the infection of single-stranded RNA viruses. The expression of cytokines and chemokines in the supernatants of above culture system was detected by ELISA and qPCR. On days 4, 5, 6, 7 and 15 after infection, the body weight loss of mice in the RDN treatment group was alleviated compared with that of PR8-infected mice(P<0.05). RDN treatment obviously reduced lung index and the production of IL-6, TNF-α, MCP-1 and MIP-2 in lung tissues of flu-infected mice(P<0.05). The proportions of macrophages, neutrophils and T cells in mouse BALF samples were analyzed by flow cytometry, and compared with PR8-infected mice, RDN decreased the proportion of macrophages in BALF of flu-infected mice(P<0.05), and the proportion of T cells was recovered dramatically(P<0.001). In CCK-8 assay, the concentrations of RDN(150, 300, 600 µg·mL~(-1)) failed to cause cytotoxicity to RAW264.7 cells. In addition, RDN lowered the expression of inflammatory cytokines such as IL-6, TNF-α,MCP-1, IL-1ß, RANTES, and IP-10 and even anti-inflammatory cytokine IL-10 in R837-induced macrophages. RDN reduced the infiltration of inflammatory macrophages and the production of excessive inflammatory cytokines, alleviated the body weight loss of flu-infected mice. What's more, RDN restored the depletion of T cells, which might prevent secondary infection and deteriorative progression of the disease. Taken together, RDN may inhibit cytokine production and therefore down-regulate cytokine storm during the infection of influenza virus.
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Interleucina-10 , Oseltamivir , Animales , Antiinflamatorios/farmacología , Peso Corporal , Quimiocina CCL5/farmacología , Quimiocina CXCL10/farmacología , Síndrome de Liberación de Citoquinas , Citocinas/genética , Medicamentos Herbarios Chinos , Femenino , Imiquimod/farmacología , Interleucina-6 , Pulmón , Ratones , Ratones Endogámicos C57BL , Oseltamivir/farmacología , Fosfatos/farmacología , ARN , ARN Mensajero , Factor de Necrosis Tumoral alfa/genética , Pérdida de PesoRESUMEN
Metal nitride complexes have recently been proposed as an efficient noble-metal-free catalyst for ammonia synthesis utilizing a dual active site concept. However, their high sensitivity to air and moisture has restricted potential applications. We report that their chemical sensitivity can be improved by introducing Al into the LaN lattice, thereby forming La-Al metallic bonds (La-Al-N). The catalytic activity and mechanism of the resulting TM/La-Al-N (TM=Ni, Co) are comparable to the previously reported TM/LaN catalyst. Notably, the catalytic activity did not degrade after exposure to air and moisture. Kinetic analysis and isotopic experiment showed that La-Al-N is responsible for N2 absorption and activation despite substantial Al being introduced into its lattice because the local coordination of the lattice N remained largely unchanged. These findings show the effectiveness of metallic bond formation, which can support the chemical stability of rare-earth nitrides with retention of catalytic functionality.
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The current catalytic reaction mechanism for ammonia synthesis relies on either dissociative or associative routes, in which adsorbed N2 dissociates directly or is hydrogenated step-by-step until it is broken upon the release of NH3 through associative adsorption. Here, we propose a concerted mechanism of associative and dissociative routes for ammonia synthesis over a cobalt-loaded nitride catalyst. Isotope exchange experiments reveal that the adsorbed N2 can be activated on both Co metal and the nitride support, which leads to superior low-temperature catalytic performance. The cooperation of the surface low work function (2.6 eV) feature and the formation of surface nitrogen vacancies on the CeN support gives rise to a dual pathway for N2 activation with much reduced activation energy (45 kJ·mol-1) over that of Co-based catalysts reported so far, which results in efficient ammonia synthesis under mild conditions.