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The nucleus of almost all massive galaxies contains a supermassive black hole (BH)1. The feedback from the accretion of these BHs is often considered to have crucial roles in establishing the quiescence of massive galaxies2-14, although some recent studies show that even galaxies hosting the most active BHs do not exhibit a reduction in their molecular gas reservoirs or star formation rates15-17. Therefore, the influence of BHs on galaxy star formation remains highly debated and lacks direct evidence. Here, based on a large sample of nearby galaxies with measurements of masses of both BHs and atomic hydrogen (HI), the main component of the interstellar medium18, we show that the HI gas mass to stellar masses ratio (µHI = MHI/Mâ) is more strongly correlated with BH masses (MBH) than with any other galaxy parameters, including stellar mass, stellar mass surface density and bulge masses. Moreover, once the µHI-MBH correlation is considered, µHI loses dependence on other galactic parameters, demonstrating that MBH serves as the primary driver of µHI. These findings provide important evidence for how the accumulated energy from BH accretion regulates the cool gas content in galaxies, by ejecting interstellar medium gas and/or suppressing gas cooling from the circumgalactic medium.
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Most structural and evolutionary properties of galaxies strongly rely on the stellar initial mass function (IMF), namely the distribution of the stellar mass formed in each episode of star formation1-4. The IMF shapes the stellar population in all stellar systems, and so has become one of the most fundamental concepts of modern astronomy. Both constant and variable IMFs across different environments have been claimed despite a large number of theoretical5-7 and observational efforts8-15. However, the measurement of the IMF in Galactic stellar populations has been limited by the relatively small number of photometrically observed stars, leading to high uncertainties12-16. Here we report a star-counting result based on approximately 93,000 spectroscopically observed M-dwarf stars, an order of magnitude more than previous studies, in the 100-300 parsec solar neighbourhood. We find unambiguous evidence of a variable IMF that depends on both metallicity and stellar age. Specifically, the stellar population formed at early times contains fewer low-mass stars compared with the canonical IMF, independent of stellar metallicities. In more recent times, however, the proportion of low-mass stars increases with stellar metallicity. The variable abundance of low-mass stars in our Milky Way establishes a powerful benchmark for models of star formation and can heavily affect results in Galactic chemical-enrichment modelling, mass estimation of galaxies and planet-formation efficiency.
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Ferroptosis is a mode of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation. It is closely linked to the pathophysiological processes in many diseases. Since our publication of the first ferroptosis database in 2020 (FerrDb V1), many new findings have been published. To keep up with the rapid progress in ferroptosis research and to provide timely and high-quality data, here we present the successor, FerrDb V2. It contains 1001 ferroptosis regulators and 143 ferroptosis-disease associations manually curated from 3288 articles. Specifically, there are 621 gene regulators, of which 264 are drivers, 238 are suppressors, 9 are markers, and 110 are unclassified genes; and there are 380 substance regulators, with 201 inducers and 179 inhibitors. Compared to FerrDb V1, curated articles increase by >300%, ferroptosis regulators increase by 175%, and ferroptosis-disease associations increase by 50.5%. Circular RNA and pseudogene are novel regulators in FerrDb V2, and the percentage of non-coding RNA increases from 7.3% to 13.6%. External gene-related data were integrated, enabling thought-provoking and gene-oriented analysis in FerrDb V2. In conclusion, FerrDb V2 will help to acquire deeper insights into ferroptosis. FerrDb V2 is freely accessible at http://www.zhounan.org/ferrdb/.
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Ferroptose , Ferroptose/genética , Confiabilidade dos Dados , Bases de Dados Factuais , Peroxidação de Lipídeos , PseudogenesRESUMO
After the aluminum alloy mirror machined by single point diamond turning (SPDT), the residual tool marks and surface accuracy of the aluminum alloy mirror cannot meet the requirements of visible or ultraviolet light system. In this study, a processing method combining magnetorheological finishing (MRF) and chemical mechanical polishing (CMP) is proposed to realize the polishing of aluminum alloy mirrors with high efficiency, high precision and high-quality. Firstly, the properties and composition of passivation layer after MRF were analyzed and the polishing performance of acidic, neutral and alkaline alumina polishing fluid on passivation layer were investigated based on the computer numerical control (CNC) polishing equipment. Based on the experimental results, a new acidic nano-silica polishing fluid which is suitable for the efficient and high-quality removal of passivation layers on aluminum alloy surfaces was developed. Finally, a combined approach of MRF-CMP was used to the directly polishing of a rapidly solidified aluminum mirror (RSA-6061) with a diameter of 100 mm after SPDT. With two iterative of MRF-CMP polishing in 220 minutes, the surface accuracy of the aluminum alloy mirror was improved from 0.1λ (λ=632.8â nm) to 0.024λ, and the surface roughness (Ra) decreased from 3.6â nm to 1.38â nm. The experiment results manifest that high precision, and high-quality aluminum alloy mirror can be achieved by MRF-CMP method with the new developed acid nano-silica polishing fluid and suitable MR polishing fluid. The research results will provide a new strategy for ultra-precision direct polishing of aluminum alloy mirrors and will also give the important technical support for the extensive use of aluminum alloy mirror in visible light and ultraviolet optical systems.
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The diffraction efficiency, defined as the ratio of diffracted power to incident power, is one of the key working indicators for a computer-generated hologram (CGH). The CGH with high diffraction efficiency could suppress stray light and eliminate ghost images, thus improving interferometric performance in aspherical testing of low-reflectivity or large off-axis distance surfaces. However, the high-efficiency CGH is hard to precisely fabricate by traditional reactive ion etching and focusing ion beam, because it requires high etching depth with a high uniformity and sub-nanometric roughness in the glass, especially in the fabrication of a large CGH with an aperture of up to 300 mm. In this study, fabrication of the above-mentioned CGH was demonstrated via what we believe to be a new method called scanning homogenization etching (SHE), in which the ion source with a Gaussian energy distribution accurately scans the glass surface to realize homogenization etching. Different from controlling dwell time at each etching point, this paper proposes to control the scanning rate to achieve not only uniform but also quantitative depth removal in a single scan. Moreover, the depth errors in deep etching across the whole glass surface can be remarkably reduced due to homogenization effects introduced by multiple scanning etching. Finally, the target etching depth of 692.3â nm with an etching uniformity of 2.2% in the etching of a 300 mm CGH was achieved. The roughness of the etched and unetched area both have Ra values of 0.3â nm. The diffraction efficiency of working order is 39.998%, achieving 98.6% of the theoretical diffraction efficiency. In addition, the SHE is not limited by the aperture of the ion source, so it can achieve even larger diffractive optical elements with high diffraction efficiency and high accuracy.
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OBJECTIVE: This study aimed to explore the effect of CD276 expression on the sunitinib sensitivity of clear cell renal cell carcinoma (ccRCC) cell and animal models and the potential mechanisms involved. METHODS: CD276 expression levels of ccRCC and normal samples were analyzed via online databases and real-time quantitative PCR (RT-qPCR). CD276 was knocked down in ccRCC cell models (sunitinib-resistant 786-O/R cells and sunitinib-sensitive 786-O cells) using shRNA transfection, and the cells were exposed to a sunitinib (2 µM) environment. Cells proliferation was then analyzed using MTT assay and colony formation experiment. Alkaline comet assay, immunofluorescent staining, and western blot experiments were conducted to assess the DNA damage repair ability of the cells. Western blot was also used to observe the activation of FAK-MAPK pathway within the cells. Finally, a nude mouse xenograft model was established and the nude mice were orally administered sunitinib (40 mg/kg/d) to evaluate the in vivo effects of CD276 knockdown on the therapeutic efficacy of sunitinib against ccRCC. RESULTS: CD276 was significantly upregulated in both ccRCC clinical tissue samples and cell models. In vitro experiments showed that knocking down CD276 reduced the survival rate, IC50 value, and colony-forming ability of ccRCC cells. Knocking down CD276 increased the comet tail moment (TM) values and γH2AX foci number, and reduced BRCA1 and RAD51 protein levels. Knocking down CD276 also decreased the levels of p-FAK, p-MEK, and p-ERK proteins. CONCLUSION: Knocking down CD276 effectively improved the sensitivity of ccRCC cell and animal models to sunitinib treatment.
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Carcinoma de Células Renais , Dano ao DNA , Reparo do DNA , Resistencia a Medicamentos Antineoplásicos , Neoplasias Renais , Camundongos Nus , Sunitinibe , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Humanos , Sunitinibe/farmacologia , Sunitinibe/uso terapêutico , Animais , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Camundongos , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quinase 1 de Adesão Focal/metabolismo , Quinase 1 de Adesão Focal/genética , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Feminino , Técnicas de Silenciamento de Genes , Masculino , Antígenos B7RESUMO
High hyperdiploid karyotype with ≥ 49 chromosomes (which will be referred to as HHK) is rare in acute myeloid leukemia (AML). The European leukemia network (ELN) excluded those harboring only numerical changes (with ≥ 3 chromosome gains) from CK and listed them in the intermediate risk group, while the UK National Cancer Research Institute Adult Leukaemia Working Group classification defined ≥ 4 unrelated chromosome abnormalities as the cutoff for a poorer prognosis. Controversies occurred among studies on the clinical outcome of HHK AML, and their molecular characteristics remained unstudied. We identified 1.31% (133/10,131) HHK cases within our center, among which 48 cases only had numerical changes (NUM), 42 had ELN defined adverse abnormalities (ADV) and 43 had other structural abnormalities (STR). Our study demonstrated that: (1) No statistical significance for overall survival (OS) was observed among three cytogenetic subgroups (NUM, STR and ADV) and HHK AML should be assigned to the adverse cytogenetic risk group. (2) The OS was significantly worse in HHK AML with ≥ 51 chromosomes compared with those with 49-50 chromosomes. (3) The clinical characteristics were similar between NUM and STR group compared to ADV group. The former two groups had higher white blood cell counts and blasts, lower platelet counts, and mutations associated with signaling, while the ADV group exhibited older age, higher chromosome counts, higher percentage of myelodysplastic syndrome (MDS) history, and a dominant TP53 mutation.
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Leucemia Mieloide Aguda , Mutação , Proteína Supressora de Tumor p53 , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/diagnóstico , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Idoso , Proteína Supressora de Tumor p53/genética , China/epidemiologia , Prognóstico , Adolescente , Adulto Jovem , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Cariótipo , Taxa de Sobrevida , CariotipagemRESUMO
OBJECTIVE: This study aimed to explore the relationship between CD276 and clear cell renal carcinoma (ccRCC) and assess the diagnostic value of CD276 in ccRCC. METHODS: Expression levels of CD276 in ccRCC and para-cancer tissues were compared and analyzed retrospectively using data obtained from TCGA and GEO databases. The clinical data was analyzed prospectively. Immunohistochemistry and RT-PCR analyses were used to analyze the expression of CD276 at the mRNA and protein levels. These analyses compared the expression between ccRCC tissues and para-cancer tissues obtained from 70 patients with ccRCC. Next, ELISA was used to analyze peripheral blood samples from 70 patients with ccRCC and 72 healthy individuals, facilitating the differentiation of ccRCC patients from normal controls. Finally, we utilized the Kaplan-Meier method to generate ROC curves for assessing the diagnostic value of CD276 for ccRCC. RESULTS: Analysis of TCGA and GEO data revealed that the mRNA expression of CD276 was higher in ccRCC tissues than in para-cancer tissues (P < .05). Clinical validation using IHC and RT-PCR confirmed that the expression of CD276 was higher in ccRCC tissues than in para-cancer tissues, both at the mRNA and protein levels (P < .05). ELISA demonstrated that the expression of CD276 was higher in ccRCC patients than in normal individuals, and patients with a higher pathological grade showed higher expression of CD276 in the peripheral blood than those with a lower pathological grade (P < .05). ROC curves drawn from the above three datasets demonstrated that CD276 had a high diagnostic value for ccRCC (AUC = .894, .795, .938, respectively). CONCLUSION: The expression of CD276 was higher in ccRCC tissues and positively associated with the pathological grade. Therefore, CD276 may serve as a molecular biomarker for ccRCC prediction.
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Antígenos B7 , Biomarcadores Tumorais , Carcinoma de Células Renais , Biologia Computacional , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/patologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Antígenos B7/genética , Antígenos B7/sangue , Masculino , Feminino , Neoplasias Renais/diagnóstico , Neoplasias Renais/sangue , Neoplasias Renais/genética , Neoplasias Renais/patologia , Biologia Computacional/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Curva ROC , Idoso , Regulação Neoplásica da Expressão Gênica , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/sangue , Estudos de Casos e ControlesRESUMO
All measurements of cosmic star formation must assume an initial distribution of stellar masses-the stellar initial mass function-in order to extrapolate from the star-formation rate measured for typically rare, massive stars (of more than eight solar masses) to the total star-formation rate across the full stellar mass spectrum 1 . The shape of the stellar initial mass function in various galaxy populations underpins our understanding of the formation and evolution of galaxies across cosmic time 2 . Classical determinations of the stellar initial mass function in local galaxies are traditionally made at ultraviolet, optical and near-infrared wavelengths, which cannot be probed in dust-obscured galaxies2,3, especially distant starbursts, whose apparent star-formation rates are hundreds to thousands of times higher than in the Milky Way, selected at submillimetre (rest-frame far-infrared) wavelengths4,5. The 13C/18O isotope abundance ratio in the cold molecular gas-which can be probed via the rotational transitions of the 13CO and C18O isotopologues-is a very sensitive index of the stellar initial mass function, with its determination immune to the pernicious effects of dust. Here we report observations of 13CO and C18O emission for a sample of four dust-enshrouded starbursts at redshifts of approximately two to three, and find unambiguous evidence for a top-heavy stellar initial mass function in all of them. A low 13CO/C18O ratio for all our targets-alongside a well tested, detailed chemical evolution model benchmarked on the Milky Way 6 -implies that there are considerably more massive stars in starburst events than in ordinary star-forming spiral galaxies. This can bring these extraordinary starbursts closer to the 'main sequence' of star-forming galaxies 7 , although such main-sequence galaxies may not be immune to changes in initial stellar mass function, depending on their star-formation densities.
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BACKGROUND: Unfavourable lipid and glucose levels may play a crucial role in the pathogenesis of gestational diabetes mellitus (GDM). However, there is a lack of prospective studies on the relationship between lipid profiles, lipid ratios and GDM during pregnancy. AIMS: To prospectively investigate the relationship between lipid profile and lipid ratios in early and mid-pregnancy and their pattern of change from early to mid-pregnancy and the risk of GDM. METHODS: This nested case-control study was based on maternal and child healthcare hospitals from Fujian Province, China. We included pregnant women who delivered in the hospital from January 2021 to June 2023. Lipid profiles (TC, TG, ApoA1, ApoB, HDL-c, LDL-c) and fasting glucose were measured before 14 weeks of gestation and between 20 and 28 weeks of gestation, and lipid ratios (triglyceride glucose index, TG/HDL-c and TC/HDL-c) was constructed. Logistic regression was used to assess the relationship between lipid profile, lipid ratios and GDM. RESULTS: Of 1586 pregnant women, 741 were diagnosed with GDM. After adjusting for potential confounders, TG, ApoA1, ApoB, LDL-c, triglyceride glucose index, TG/HDL-c, and TC/HDL-c in early pregnancy were positively associated with the risk of GDM (odds ratios [95% CI] for extreme interquartile comparisons were 2.040 (1.468-2.843), 1.506 (1.091-2.082), 1.529 (1.110-2.107), 1.504 (1.086-2.086), 1.952 (1.398-2.731), 2.127 (1.526-2.971), and 2.370 (1.700-3.312), all trend P < 0.05). HDL-c was negatively associated with the risk of GDM (0.639: 0.459-0.889, trend P all less than 0.05). Similarly, in mid-pregnancy, lower levels of HDL-c, higher levels of triglyceride glucose index, TG/HDL-c ratio, and TC/HDL-c ratio were associated with increased risk of GDM (all trends P < 0.05). Stably high levels (both ≥ median for early and mid-pregnancy) of triglyceride glucose index, TG/HDL-c and TC/HDL-c were associated with increased risk of GDM (OR [95% CI]: 2.369 (1.438-3.940), 1.588 (1.077-2.341), 1.921 (1.309-2.829), respectively). The opposite was true for HDL-c, where stable high levels were negatively associated with GDM risk (OR [95% CI]: 0.599 (0.405-0.883)). CONCLUSION: Increases in triglyceride glucose index, TG/HDL-c ratio, and TC/HDL-c ratio in early and mid-pregnancy, as well as their stable high levels from early to mid-pregnancy, are associated with a higher risk of GDM. In contrast, increased levels of HDL-c, both in early and mid-pregnancy, and their stable high levels from early to mid-pregnancy were associated with a lower risk of GDM. That highlighted their possible clinical relevance in identifying those at high risk of GDM.
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Diabetes Gestacional , Lipídeos , Humanos , Feminino , Diabetes Gestacional/sangue , Diabetes Gestacional/epidemiologia , Gravidez , Adulto , Estudos de Casos e Controles , China/epidemiologia , Lipídeos/sangue , Estudos Prospectivos , Glicemia/análise , Fatores de Risco , Triglicerídeos/sangueRESUMO
The exposure to an unhealthy environment in utero can lead to the occurrence of cardiovascular diseases in the offspring. Glucocorticoids (GC) are essential for normal development and maturation of fetal organs and is a first-line treatment for pregnant women affected by autoimmune diseases. However, excess prenatal GC exposure might program the development of fetal organs and cause a number of chronic diseases in later life. Our previous studies indicated that cardiac functions were significantly compromised in rat offspring prenatally exposed to the synthetic glucocorticoid dexamethasone (DEX), only after ischemia-reperfusion. In the present study, we further observed that DNA hypermethylation of bone morphogenetic protein 4 (Bmp4) promoter in cardiomyocytes caused by prenatal DEX exposure substantially dampened the binding activity of transcription factor HIF-1α induced by cardiac ischemia. Therefore, prenatal DEX exposure inhibits the induction of BMP4 upon I/R and attenuates the protective effects of BMP4 in cardiomyocytes, which eventually manifests as malfunction of the adult heart. Moreover, we employed two cardiac-specific Bmp4 knock-in mouse models and found that in vivo BMP4 overexpression could rescue the cardiac dysfunction caused by prenatal GC exposure. In depth mechanistic research revealed that BMP4 protects the cardiomyocytes from mitophagy and apoptosis by attenuating mitochondrial PGC-1α expression in a p-Smad and Parkin-dependent manner. These findings suggest that prenatal GC exposure increases the susceptibility of the offspring's heart to a "second strike" after birth, due to the failure of hypoxia-induced HIF-1α transactivation of the hypermethylated Bmp4 promoter in cardiomyocytes. Pretreatment with the DNA methylation inhibitor, 5-Aza-2'-deoxycytidine, could be a potential therapeutic method for this programming effect of GC exposure during pregnancy on neonatal cardiac dysfunction.
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Glucocorticoides , Cardiopatias , Animais , Feminino , Humanos , Camundongos , Gravidez , Ratos , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/farmacologia , Decitabina/metabolismo , Decitabina/farmacologia , Metilação de DNA , Glucocorticoides/metabolismo , Cardiopatias/metabolismo , Miócitos Cardíacos/metabolismo , Estresse OxidativoRESUMO
Four isocoumarin derivatives (1-4) and five phenols (5-9) were obtained from the endophytic fungus Pezicula neosporulosa VDB39, which was isolated from the branches of Vaccinium dunalianum Wight (Ericaceae). Compound 1 is a new derivative of isocoumarin. The structures were elucidated by spectroscopic methods. Single X-ray crystallography confirmed the absolute configuration of compound 1. Additionally, the antiphytopathogenic fungi activity of isocoumarin derivatives (1-4) was evaluated.
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The contamination detection technology helps in water quality management and protection in surface water. It is important to detect sudden contamination events timely from dynamic variations due to various interference factors in online water quality monitoring data. In this study, a framework named "Prediction - Detection - Judgment" is proposed with a method framework of "Time series increment - Hierarchical clustering - Bayes' theorem model". Time to detection is used as an evaluation index of contamination detection methods, along with the probability of detection and false alarm rate. The proposed method is tested with available public data and further applied in a monitoring site of a river. Results showed that the method could detect the contamination events with a 100% probability of detection, a 17% false alarm rate and a time to detection close to 4 monitoring intervals. The proposed index time to detection evaluates the timeliness of the method, and timely detection ensures that contamination events can be responded to and dealt with in time. The site application also demonstrates the feasibility and practicability of the framework proposed in this study and its potential for extensive implementation.
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Julgamento , Abastecimento de Água , Teorema de Bayes , Qualidade da Água , Poluição da ÁguaRESUMO
The mature synthetic methodologies enable us to rationally design and produce chiral nanographenes (NGs), most of which consist of multiple helical motifs. However, inherent chirality originating from twisted geometry has just emerged to be employed in chiral NGs. Herein, we report a red-emissive chiral NG constituted of orthogonally arranged two-fold twisted π-skeletons at a contorted pyrene core which contributes to optical transitions of S0âS1 and vice versa. The thus-obtained NG exhibited a robustness on its redox properties through 2e- uptake/release. The chemical oxidation generated stable radical cation whose absorption covers near-infrared I and II regions. Overall, the contorted pyrene core governs electronic nature of the chiral NG. The twist operation on NGs would be, therefore, a design strategy to alter conventional chirality induction on NGs.
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BACKGROUND: Dysfunction of pancreatic ß-cells induced by glucocorticoids contributes to diabetes mellitus development. Long noncoding RNAs (lncRNAs) have been recognized to contain short open reading frames (ORFs) that can be translated into functional small peptides. Here, we investigated whether the short peptide encoded by the lncRNA MIR7-3 host gene (MIR7-3HG) can affect dexamethasone (DEX)-induced ß-cell dysfunction. METHODS: Bioinformatics analysis was used for selection of MIR7-3HG and prediction of its protein encoding potential. The small peptide was identified by a western blot method. The cell-permeable TAT was fused into MIR7-3HG ORF to produce the cell-permeable fusion peptide (TAT-MIR7-3HG-ORF). The effects of TAT-MIR7-3HG-ORF on DEX-induced ß-cell dysfunction were evaluated by examining cell viability, apoptosis, insulin secretion, and reactive oxygen species (ROS) generation. RESULTS: DEX induced ß-TC6 cell dysfunction by impairing cell viability, insulin secretion and promoting cell apoptosis and ROS generation. The MIR7-3HG ORF could encode a 125-amino-acid-long short peptide. TAT-MIR7-3HG-ORF effectively transduced into ß-TC6 cells and attenuated DEX-induced dysfunction in ß-TC6 cells. Moreover, transduced TAT-MIR7-3HG-ORF reversed DEX-mediated inhibition of the activation of the PI3K/AKT signaling pathway. The inhibitor of the PI3K/AKT pathway partially abolished the alleviative effect of transduced TAT-MIR7-3HG-ORF on DEX-induced ß-TC6 cell dysfunction. CONCLUSION: The lncRNA MIR7-3HG encodes a short peptide, which can protect pancreatic ß-cells from DEX-induced dysfunction by activating the PI3K/AKT pathway. Our study broadens the diversity and breadth of lncRNAs in human disorders.
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Células Secretoras de Insulina , MicroRNAs , RNA Longo não Codificante , Humanos , Apoptose/genética , Dexametasona/efeitos adversos , MicroRNAs/genética , MicroRNAs/farmacologia , Peptídeos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Células Secretoras de Insulina/efeitos dos fármacosRESUMO
Nanocomposites with hierarchical pore structure hold great potentials for applications in the field of microwave-absorbing materials because of their lightweight and high-efficiency absorption properties. Herein, M-type barium ferrite (BaM) with ordered mesoporous structure (M-BaM) is prepared via a sol-gel process enhanced by mixed anionic and cationic surfactants. The surface area of M-BaM is enhanced almost ten times compared with BaM together with 40% reflection loss enhancing. Then M-BaM compounded with nitrogen-doped reduced graphene oxide (MBG) is synthesized via hydrothermal reaction in which the reduction and nitrogen doping of graphene oxide (GO) in situ occur simultaneously. Interestingly, the mesoporous structure is able to provide opportunity for reductant to enter the bulk M-BaM reducing its Fe3+ to Fe2+ and further forms Fe3 O4 . It requires an optimal balance among the remained mesopores in MBG, formed Fe3 O4 , and CN in nitrogen-doped graphene (N-RGO) for optimizing impedance matching and greatly increasing multiple reflections/interfacial polarization. MBG-2 (GO:M-BaM = 1:10) achieves the minimum reflection loss of -62.6 dB with an effective bandwidth of 4.2 GHz at an ultra-thin thickness of 1.4 mm. In addition, the marriage of mesoporous structure of M-BaM and light mass of graphene reduces the density of MBG.
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The coronavirus disease 2019 (COVID-19) pandemic posed great impacts on public health. To fight against the pandemic, robust immune responses induced by vaccination are indispensable. Previously, we developed a subunit vaccine adjuvanted by aluminum hydroxide, ZF2001, based on the dimeric tandem-repeat RBD immunogen, which has been approved for clinical use. This dimeric RBD design was also explored as an mRNA vaccine. Both showed potent immunogenicity. In this study, a DNA vaccine candidate encoding RBD-dimer was designed. The humoral and cellular immune responses induced by homologous and heterologous prime-boost approaches with DNA-RBD-dimer and ZF2001 were assessed in mice. Protection efficacy was studied by the SARS-CoV-2 challenge. We found that the DNA-RBD-dimer vaccine was robustly immunogenic. Priming with DNA-RBD-dimer followed by ZF2001 boosting induced higher levels of neutralizing antibodies than homologous vaccination with either DNA-RBD-dimer or ZF2001, elicited polyfunctional cellular immunity with a TH 1-biased polarization, and efficiently protected mice against SARS-CoV-2 infection in the lung. This study demonstrated the robust and protective immune responses induced by the DNA-RBD-dimer candidate and provided a heterologous prime-boost approach with DNA-RBD-dimer and ZF2001.
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COVID-19 , Vacinas de DNA , Vacinas Virais , Humanos , Animais , Camundongos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Anticorpos Neutralizantes , Imunidade Celular , Anticorpos AntiviraisRESUMO
Metal mirrors have attracted increasing attention for satisfying the growing demands for high-performance optics in airborne and spaceborne remote sensing systems. Additive manufacturing has enabled the development of metal mirrors with reduced weight and improved strength. AlSi10Mg is the most widely used metal for additive manufacturing. Diamond cutting is an effective method for obtaining nanometer-scale surface roughness. However, the surface/subsurface defects of additively manufactured AlSi10Mg deteriorate the surface roughness. Conventionally, AlSi10Mg mirrors used in near-infrared and visible systems are plated with NiP layers to improve the surface polishing performance; however, this leads to the bimetallic bending because of the different coefficients of thermal expansion between the NiP layers and AlSi10Mg blanks. In this study, a method of nanosecond-pulsed laser irradiation is proposed to eliminate the surface/subsurface defects of AlSi10Mg. The microscopic pores, unmolten particles and two-phase microstructure of the mirror surface were eliminated. The mirror surface exhibited better polishing performance, and it could be smoothly polished to a nanometer-scale surface roughness. The mirror exhibits strong temperature stability owing to the elimination of the bimetallic bending caused by the NiP layers. It is expected that the mirror surface fabricated in this study can satisfy the requirements for near-infrared or even visible applications.
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This paper discusses a method for assembling Au-Ag alloy nanoparticles (NPs) using direct current (DC) electric field to fabricate highly active SERS substrates. Different nanostructures could be obtained by regulating the intensity and action time of DC electric field. Under the condition of 5mA*10 min, we obtained Au-Ag alloy nano-reticulation (ANR) substrate with excellent SERS activity (Enhancement factor on order of magnitude of 106). ANR substrate has excellent SERS performance due to the resonance matching between its LSPR mode and excitation wavelength. The uniformity of the Raman signal on ANR is greatly improved than bare ITO glass. ANR substrate also has the ability to detect multiple molecules: ANR substrate can respectively detect Rh6G and CV molecules with a concentration as low as 10-10 M and 10-9 M and the Raman spectral intensity of the probe molecules on the surface of the ANR substrate has good linear correlation with the molecular concentration (R2 > 0.95). In addition, ANR substrate can detect both thiram and aspartame (APM) molecules far below (thiram for 0.0024â ppm and APM for 0.0625 g/L) the safety standard, which demonstrate its practical application potential.
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Atypical chronic myeloid leukemia (CML) is a rare BCR::ABL1-negative hematopoietic stem cell disease characterized by granulocytic proliferation and granulocytic dysplasia. Due to both the challenging diagnosis and the rarity of atypical CML, comprehensive molecular annotation-based analyses of this disease population have been scarce, and it is currently difficult to identify the optimal treatment for atypical CML. To explore atypical CML genomic landscape and treatment options, we performed a systematic retrospective of the clinical data and outcomes of 31 atypical CML patients. We observed that the molecular landscape of atypical CML was highly heterogeneous, with multiple molecular events driving its pathogenesis. Patients with atypical CML had a low response to current therapies, with an overall response rate (ORR) of 33.3% to hypomethylating agent (HMA)-based therapy. The current treatment strategies, including hematopoietic stem cell transplantation (HSCT), did not improve overall survival (OS) in atypical CML patients, with a median survival of 20 months. Thus, the benefits from HSCT and candidates for HSCT remain to be further evaluated. Acute myeloid leukemia (AML)-like chemotherapy followed by bridging allogeneic HSCT may be an ideal regimen for suitable individuals. The large-scale and prospective clinical studies will help to address the dilemma.