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Glucose consumption is generally increased in tumor cells to support tumor growth. Interestingly, we report that glycogen accumulation is a key initiating oncogenic event during liver malignant transformation. We found that glucose-6-phosphatase (G6PC) catalyzing the last step of glycogenolysis is frequently downregulated to augment glucose storage in pre-malignant cells. Accumulated glycogen undergoes liquid-liquid phase separation, which results in the assembly of the Laforin-Mst1/2 complex and consequently sequesters Hippo kinases Mst1/2 in glycogen liquid droplets to relieve their inhibition on Yap. Moreover, G6PC or another glycogenolysis enzyme-liver glycogen phosphorylase (PYGL) deficiency in both human and mice results in glycogen storage disease along with liver enlargement and tumorigenesis in a Yap-dependent manner. Consistently, elimination of glycogen accumulation abrogates liver growth and cancer incidence, whereas increasing glycogen storage accelerates tumorigenesis. Thus, we concluded that cancer-initiating cells adapt a glycogen storing mode, which blocks Hippo signaling through glycogen phase separation to augment tumor incidence.
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Carcinogênese/metabolismo , Carcinogênese/patologia , Glicogênio/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular , Modelos Animais de Doenças , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glucose-6-Fosfatase/metabolismo , Glicogênio Fosforilase/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Via de Sinalização Hippo , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Transição de Fase , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Serina-Treonina Quinase 3/metabolismo , Proteínas de Sinalização YAP/metabolismoRESUMO
Rad52 is a key factor for homologous recombination (HR) in yeast. Rad52 helps assemble Rad51-ssDNA nucleoprotein filaments that catalyze DNA strand exchange, and it mediates single-strand DNA annealing. We find that Rad52 has an even earlier function in HR in restricting DNA double-stranded break ends resection that generates 3' single-stranded DNA (ssDNA) tails. In fission yeast, Exo1 is the primary resection nuclease, with the helicase Rqh1 playing a minor role. We demonstrate that the choice of two extensive resection pathways is regulated by Rad52. In rad52 cells, the resection rate increases from â¼3-5 kb/h up to â¼10-20 kb/h in an Rqh1-dependent manner, while Exo1 becomes dispensable. Budding yeast Rad52 similarly inhibits Sgs1-dependent resection. Single-molecule analysis with purified budding yeast proteins shows that Rad52 competes with Sgs1 for DNA end binding and inhibits Sgs1 translocation along DNA. These results identify a role for Rad52 in limiting ssDNA generated by end resection.
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Quebras de DNA de Cadeia Dupla , Quebras de DNA de Cadeia Simples , Reparo do DNA , DNA Fúngico/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteína Rad52 de Recombinação e Reparo de DNA/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/enzimologia , DNA Helicases/genética , DNA Helicases/metabolismo , DNA Fúngico/genética , Proteínas de Ligação a DNA/genética , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Regulação Fúngica da Expressão Gênica , Cinética , Mutação , Domínios Proteicos , Transporte Proteico , Proteína Rad52 de Recombinação e Reparo de DNA/genética , RecQ Helicases/genética , RecQ Helicases/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genéticaRESUMO
SUMMARY: Recent technical advancements in single-cell chromatin accessibility sequencing (scCAS) have brought new insights to the characterization of epigenetic heterogeneity. As single-cell genomics experiments scale up to hundreds of thousands of cells, the demand for computational resources for downstream analysis grows intractably large and exceeds the capabilities of most researchers. Here, we propose EpiCarousel, a tailored Python package based on lazy loading, parallel processing, and community detection for memory- and time-efficient identification of metacells, i.e. the emergence of homogenous cells, in large-scale scCAS data. Through comprehensive experiments on five datasets of various protocols, sample sizes, dimensions, number of cell types, and degrees of cell-type imbalance, EpiCarousel outperformed baseline methods in systematic evaluation of memory usage, computational time, and multiple downstream analyses including cell type identification. Moreover, EpiCarousel executes preprocessing and downstream cell clustering on the atlas-level dataset with 707 043 cells and 1 154 611 peaks within 2 h consuming <75 GB of RAM and provides superior performance for characterizing cell heterogeneity than state-of-the-art methods. AVAILABILITY AND IMPLEMENTATION: The EpiCarousel software is well-documented and freely available at https://github.com/biox-nku/epicarousel. It can be seamlessly interoperated with extensive scCAS analysis toolkits.
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Cromatina , Análise de Célula Única , Software , Cromatina/metabolismo , Análise de Célula Única/métodos , Humanos , Genômica/métodos , Biologia Computacional/métodosRESUMO
Populus cathayana × canadansis 'Xinlin 1' ('P.'xin lin 1') with the characteristics of rapid growth and high yield, is frequently attacked by herbivorous insects. However, little is known about how it defenses against Hyphantria cunea (H. cunea) at molecular and biochemical levels. Differences in the transcriptome and metabolome were analyzed after 'P. 'xin lin 1' leaves were fed to H. cunea for 0h, 2h, 4h, 8h, 16h and 24h. In the five comparison groups including 2h vs. CK, 4h vs. CK, 8h vs. CK, 16h vs. CK, and 24h vs. CK, a total of 8925 genes and 842 metabolites were differentially expressed. A total of 825 transcription factors (TFs) were identified, which encoded 56 TF families. The results showed that the top four families with the highest number of TFs were AP2/ERF, MYB, C2C2, bHLH. Analyses of leaves which were fed to H. cunea showed that the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were significantly enriched in plant hormone signal transduction pathway, MAPK signaling pathway, flavonoid, flavone and flavonol and anthocyanin biosynthesis pathway. Additionally, there were a number of genes significantly up-regulated in MAPK signaling pathway. Some compounds involved in plant hormone signal transduction and flavonoid/flavone and flavonol/ anthocyanin pathways such as jasmonic acid (JA), jasmonoyl-L-Isoleucine (JA-Ile), kaempferol and cyanidin-3-O-glucoside were induced in infested 'P.'xin lin 1'. This study provides a new understanding for exploring the dynamic response mechanism of poplar to the infestation of H. cunea.
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Populus , Transcriptoma , Populus/genética , Populus/metabolismo , Herbivoria , Animais , Metaboloma , Regulação da Expressão Gênica de Plantas , Folhas de Planta/metabolismo , Folhas de Planta/genética , Perfilação da Expressão Gênica , Metabolômica , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genéticaRESUMO
Perovskite oxides are proven as a striking platform for developing high-performance electrocatalysts. Nonetheless, a significant portion of them show CO2 electroreduction (CO2RR) inertness. Here a simple but effective strategy is reported to activate inert perovskite oxides (e.g., SrTiO3) for CO2RR through slight Cu2+ doping in B-sites. For the proof-of-concept catalysts of SrTi1-xCuxO3 (x = 0.025, 0.05, and 0.1), Cu2+ doping (even in trace amount, e.g., x = 0.025) can not only create active, stable CuO6 octahedra, increase electrochemical active surface area, and accelerate charge transfer, but also significantly regulate the electronic structure (e.g., up-shifted band center) to promote activation/adsorption of reaction intermediates. Benefiting from these merits, the stable SrTi1-xCuxO3 catalysts feature great improvements (at least an order of magnitude) in CO2RR activity and selectivity for high-order products (i.e., CH4 and C2+), compared to the SrTiO3 parent. This work provides a new avenue for the conversion of inert perovskite oxides into high-performance electrocatalysts toward CO2RR.
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A highly viable alternative to lithium-ion batteries for stationary electrochemical energy-storage systems is the potassium dual-ion hybrid capacitor (PIHC), especially toward fast-charging capability. However, the sluggish reaction kinetics of negative electrode materials seriously impedes their practical implementation. In this paper, a new negative electrode Bi@RPC (Nano-bismuth confined in nitrogen- and oxygen-doped carbon with rationally designed pores, evidenced by advanced characterization) is developed, leading to a remarkable electrochemical performance. PIHCs building with the active carbon YP50F positive electrode result in a high operation voltage (0.1-4 V), and remarkably well-retained energy density at a high-power density (11107 W kg-1 at 98 Wh kg-1). After 5000 cycles the proposed PHICs still show a superior capacity retention of 92.6%. Moreover, a reversible mechanism of "absorption-alloying" of the Bi@RPC nanocomposite is revealed by operando synchrotron X-ray diffraction and Raman spectroscopy. With the synergistic potassium ions storage mechanism arising from the presence of well-structured pores and nano-sized bismuth, the Bi@RPC electrode exhibits an astonishingly rapid kinetics and high energy density. The results demonstrate that PIHCs with Bi@RPC-based negative electrode is the promising option for simultaneously high-capacity and fast-charging energy storage devices.
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All-hydrogel supercapacitors are emerging as promising power sources for next-generation wearable electronics due to their intrinsic mechanical flexibility, eco-friendliness, and enhanced safety. However, the insufficient interfacial adhesion between the electrode and electrolyte and the frozen hydrogel matrices at subzero temperatures largely limit the practical applications of all-hydrogel supercapacitors. Here, an all-hydrogel supercapacitor is reported with robust interfacial contact and anti-freezing property, fabricated by in situ polymerizing hydrogel electrolyte onto hydrogel electrodes. The robust interfacial adhesion is developed by the synergistic effect of a tough hydrogel matrix and topological entanglements. Meanwhile, the incorporation of zinc chloride (ZnCl2) in the hydrogel electrolyte prevents the freezing of water solvents and endows the all-hydrogel supercapacitor with mechanical flexibility and fatigue resistance across a wide temperature range of 20 °C to -60 °C. Such all-hydrogel supercapacitor demonstrates satisfactory low-temperature electrochemical performance, delivering a high energy density of 11 mWh cm-2 and excellent cycling stability with a capacitance retention of 90% over 10000 cycles at -40 °C. Notably, the fabricated all-hydrogel supercapacitor can endure dynamic deformations and operate well under 2000 tension cycles even at -40 °C, without experiencing delamination and electrochemical failure. This work offers a promising strategy for flexible energy storage devices with low-temperature adaptability.
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Reacting RE2O3 and H3BO3 in an ultra-alkaline NaOH hydroflux at about 250 °C yielded pure, crystalline samples of Na2[RE(BO3)(OH)2] (RE=Y, Gd-Er). The compounds dehydrate to Na3RE(BO3)2 upon heating in air to about 500 °C. Na2[RE(BO3)(OH)2] (RE=Tb-Er) are photoluminescent under UV radiation. Their UV-Vis spectra show the typical absorptions associated with 4f-4f transitions and absorption edges in the UV (band gaps ≥5.7â eV). The RE3+ cation is coordinated by seven oxygen atoms, which define a distorted pentagonal bipyramid. The bipyramids share trans-edges of their base forming infinite chains. Triangular (BO3)3- groups connect the chains into layers. The crystal structure of Na2[Ho(BO3)(OH)2] was investigated at various temperatures in the range 100â K≤T≤320â K. Above 310(2)â K, the compound crystallizes in the orthorhombic space group Cmcm (ß-phase), below, it undergoes a displacive phase transition of second order resulting in a monoclinic structure in space group C2/c (α-phase). The critical exponents derived from different structural parameters indicate a cooperative distortion of the borate layers, but a rather uncorrelated adaptation of the sodium cations to their local environment. The other compounds of the series also adopt the structure of the α-phase at 296â K.
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INTRODUCTION: Type 2 diabetes (T2DM) and major depressive disorder (MDD) together occur frequently among the elderly population. However, the inconsistency in assessments and limited medical resources in the community make it challenging to identify depression in patients with T2DM. This cross-sectional study aimed to investigate the activation pattern and network connectivity of prefrontal cortex (PFC) during a verbal fluency task (VFT) in patients with T2DM and MDD using functional near-infrared spectroscopy (fNIRS). METHODS: Three parallel groups (T2DM with MDD group, T2DM group, and healthy group) with 100 participants in each group were included in the study. Recruitment took place from August 1, 2020, to December 31, 2023. Due to the close association between the PFC and depressive emotions, fNIRS was used to monitor brain activation and network connectivity of PFC in all participants during a task of Chinese-language phonological VFT. Network-based statistic prediction (NBS-predict) was adopted as data analysis method. RESULTS: Patients in the T2DM with MDD group showed characteristic activation pattern and network connectivity in contrast with patients with T2MD and healthy controls, including decreased activation in PFC, and decreased network connectivity of right dorsolateral prefrontal cortex (DLPFC). Furthermore, the network connectivity of the right DLPFC in patients with T2DM and MDD was negatively correlated with scores of Hamilton Depression Scale-24 (HAMD-24). CONCLUSIONS: There was a distinctive activation pattern and network connectivity of the prefrontal cortex in patients with T2DM and MDD. The right DLPFC could serve as a potential target for the diagnosis and intervention of MDD in patients with T2DM.
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BACKGROUND: The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety. METHODS: A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators. RESULTS: A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43-1.56, P = 0.544). CONCLUSION: Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results. TRIAL REGISTRATION: Retrospectively registered in PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023388860 .
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Antituberculosos , Dexametasona , Quimioterapia Combinada , Injeções Espinhais , Isoniazida , Tuberculose Meníngea , Humanos , Tuberculose Meníngea/tratamento farmacológico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Isoniazida/administração & dosagem , Isoniazida/uso terapêutico , Isoniazida/efeitos adversos , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , Injeções Espinhais/métodos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
Lithium, a representative alkali metal, holds the coveted status of the "holy grail" in the realm of next-generation rechargeable batteries, owing to its remarkable theoretical specific capacity and low electrode potential. However, the inherent reactivity of Li metal inevitably results in the formation of the solid-electrolyte interphase (SEI) on its surface, adding complexity to the Li electrodeposition process compared to conventional metal electrodeposition. Attaining uniform Li deposition is crucial for ensuring stable, long-cycle performance and high Coulombic efficiency in Li metal batteries, which requires a comprehensive understanding of the underlying factors governing the electrodeposition process. This review delves into the intricate kinetics of Li electrodeposition, elucidating the multifaceted factors that influence charge and mass transfer kinetics. The intrinsic relationship between charge transfer kinetics and Li deposition is scrutinized, exploring how parameters such as current density and electrode potential impact Li nucleation and growth, as well as dendrite formation. Additionally, the applicability of classical mass-transfer-controlled electrodeposition models to Li anode systems is evaluated, considering the influence of ionic concentration and solvation structure on Li+ transport, SEI formation, and subsequent deposition kinetics. The pivotal role of SEI compositional structure and physicochemical properties in governing charge and mass transfer processes is underscored, with an emphasis on strategies for regulating Li deposition kinetics from both electrolyte and SEI perspectives. Finally, future directions in Li electrodeposition research are outlined, emphasizing the importance of ongoing exploration from a kinetic standpoint to fully unlock the potential of Li metal batteries.
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Low back pain (LBP) is the leading cause of disability worldwide, with a strong correlation to intervertebral disc degeneration (IDD). Inflammation-induced extracellular matrix (ECM) degradation plays a major role in IDD's progression. Emodin, known for its anti-inflammatory effects and ability to inhibit ECM degradation in osteoarthritis, but its role in IDD is unclear. Our study aimed to explore emodin's role and mechanisms on IDD both in vivo and in vitro. We discovered that emodin positively regulated anabolic markers (COL2A1, aggrecan) and negatively impacted catabolic markers (MMP3, MMP13) in nucleus pulposus cells, while also inhibiting cell apoptosis under inflammation environment. We revealed that emodin inhibits inflammation-induced NF-ĸB activation by suppressing the degradation of LRP1 via the proteasome pathway. Additionally, LRP1 was validated as essential to emodin's regulation of ECM metabolism and apoptosis, both in vitro and in vivo. Ultimately, we demonstrated that emodin effectively alleviates IDD in a rat model. Our findings uncover the novel pathway of emodin inhibiting ECM degradation and apoptosis through the inhibition of NF-κB via LRP1, thus alleviating IDD. This study not only broadens our understanding of emodin's role and mechanism in IDD treatment but also guides future therapeutic interventions.
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Cannabidiol (CBD), one of the major components extracted from the plant Cannabis sativa L., has been used as a prescription drug to treat seizures in many countries. CBD-induced male reproductive toxicity has been reported in animal models; however, the underlying mechanisms remain unclear. We previously reported that CBD induced apoptosis in primary human Leydig cells, which constitute the primary steroidogenic cell population in the testicular interstitium. In this study, we investigated the effects of CBD and its metabolites on TM3 mouse Leydig cells. CBD, at concentrations below 30 µM, reduced cell viability, induced G1 cell cycle arrest, and inhibited DNA synthesis. CBD induced apoptosis after exposure to high concentrations (≥ 50 µM) for 24 h or a low concentration (20 µM) for 6 days. 7-Hydroxy-CBD and 7-carboxy-CBD, the main CBD metabolites of CBD, exhibited the similar toxic effects as CBD. In addition, we conducted a time-course mRNA-sequencing analysis in both primary human Leydig cells and TM3 mouse Leydig cells to understand and compare the mechanisms underlying CBD-induced cytotoxicity. mRNA-sequencing analysis of CBD-treated human and mouse Leydig cells over a 5-day time-course indicated similar responses in both cell types. Mitochondria and lysosome dysfunction, oxidative stress, and autophagy were the major enriched pathways in both cell types. Taken together, these findings demonstrate comparable toxic effects and underlying mechanisms in CBD-treated mouse and primary human Leydig cells.
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Apoptose , Canabidiol , Sobrevivência Celular , Células Intersticiais do Testículo , Canabidiol/toxicidade , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Animais , Humanos , Camundongos , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Células CultivadasRESUMO
Abundant studies have explored the relations among deviant peer affiliation, self-control, and aggression without separating within-person from between-person effects. Moreover, it is unclear whether self-control mediates the associations between deviant peer affiliation and aggression during early adolescence. This longitudinal study used Random Intercept Cross-Lagged Panel Model to examine the dynamic relations among deviant peer affiliation, self-control, and aggression within individuals, including examining whether self-control mediated the relations between deviant peer affiliation and aggression. A total of 4078 early adolescents (54% boys, Mage = 9.91, SD = 0.73) completed questionnaires on four occasions across 2 years. Results indicated: (a) Deviant peer affiliation and aggression positively predicted each other; (b) Self-control and aggression negatively predicted each other but were unstable; (c) Deviant peer affiliation and self-control negatively predicted each other; and (d) Self-control mediated the path from aggression to deviant peer affiliation, but not vice versa. The results more precisely identify the relations among deviant peer affiliation, self-control, and aggression within individuals, providing valuable information for prevention and intervention programs targeted at alleviating early adolescent aggression.
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Comportamento do Adolescente , Agressão , Grupo Associado , Autocontrole , Humanos , Agressão/psicologia , Masculino , Feminino , Autocontrole/psicologia , Criança , Estudos Longitudinais , Adolescente , Comportamento do Adolescente/psicologia , Inquéritos e QuestionáriosRESUMO
The action of wind and waves has a significant effect on the ship's roll, which can be a source of chaos and even capsize. The influence of random wave excitation is considered in order to investigate complex dynamic behavior by analytical and numerical methods. Chaotic rolling motions are theoretically studied in detail by means of the relevant Melnikov method with or without noise excitation. Numerical simulations are used to verify and analyze the appropriate parameter excitation and noise conditions. The results show that by changing the parameters of the excitation amplitude or the noise intensity, chaos can be induced or suppressed.
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A graphene-based tunable polarization conversion metasurface (PCM) was designed and analyzed for the purpose of reducing the radar cross-section (RCS) of array antennas. The metasurface comprises periodic shuttle-shaped metal patches, square-patterned graphene, and inclined grating-patterned graphene. By adjusting the Fermi energy levels of the upper (µ1) and lower (µ2) graphene layers, different states were achieved. In State 1, with µ1 = 0 eV and µ2 = 0.5 eV, the polarization conversion ratio (PCR) exceeded 0.9 in the bandwidths of 1.65-2.19 THz and 2.29-2.45 THz. In State 2, with µ1 = µ2 = 0.5 eV, the PCR was greater than 0.9 in the 1.23-1.85 THz and 2.24-2.60 THz bands. In State 3, with µ1 = µ2 = 1 eV, the PCR exceeded 0.9 in the 2.56-2.75 THz and 3.73-4.05 THz bands. By integrating the PCM with the array antenna, tunable RCS reduction was obtained without affecting the basic radiation functionality of the antenna. In State 1, RCS reduction was greater than 10 dB in the 1.60-2.43 THz and 3.63-3.72 THz frequency ranges. In State 2, the RCS reduction exceeded 10 dB in the 2.07-2.53 THz, 2.78-2.98 THz, and 3.70-3.81 THz bands. In State 3, RCS reduction was greater than 10 dB in the 1.32-1.43 THz, 2.51-2.76 THz, and 3.76-4.13 THz frequency ranges. This polarization conversion metasurface shows significant potential for applications in switchable and tunable antenna RCS reduction.
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RNA is a promising nucleic acid-based biomolecule for various treatments because of its high efficacy, low toxicity, and the tremendous availability of targeting sequences. Nevertheless, RNA shows instability and has a short half-life in physiological environments such as the bloodstream in the presence of RNAase. Therefore, developing reliable delivery strategies is important for targeting disease sites and maximizing the therapeutic effect of RNA drugs, particularly in the field of immunotherapy. In this mini-review, we highlight two major approaches: (1) delivery vehicles and (2) chemical modifications. Recent advances in delivery vehicles employ nanotechnologies such as lipid-based nanoparticles, viral vectors, and inorganic nanocarriers to precisely target specific cell types to facilitate RNA cellular entry. On the other hand, chemical modification utilizes the alteration of RNA structures via the addition of covalent bonds such as N-acetylgalactosamine or antibodies (antibody-oligonucleotide conjugates) to target specific receptors of cells. The pros and cons of these technologies are enlisted in this review. We aim to review nucleic acid drugs, their delivery systems, targeting strategies, and related chemical modifications. Finally, we express our perspective on the potential combination of RNA-based click chemistry with adoptive cell therapy (e.g., B cells or T cells) to address the issues of short duration and short half-life associated with antibody-oligonucleotide conjugate drugs.
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Sistemas de Liberação de Medicamentos , Imunoterapia , RNA , Humanos , Imunoterapia/métodos , Sistemas de Liberação de Medicamentos/métodos , Animais , Nanopartículas/química , Ácidos Nucleicos/administração & dosagem , Ácidos Nucleicos/químicaRESUMO
Prussian blue analogs (PBAs) are appealing cathode materials for sodium-ion batteries because of their low material cost, facile synthesis methods, rigid open framework, and high theoretical capacity. However, the poor electrical conductivity, unavoidable presence of [Fe(CN)6] vacancies and crystalline water within the framework, and phase transition during charge-discharge result in inferior electrochemical performance, particularly in terms of rate capability and cycling stability. Here, cobalt-free PBAs are synthesized using a facile and economic co-precipitation method at room temperature, and their sodium-ion storage performance is boosted due to the reduced crystalline water content and improved electrical conductivity via the high-entropy and component stoichiometry tuning strategies, leading to enhanced initial Coulombic efficiency (ICE), specific capacity, cycling stability, and rate capability. The optimized HE-HCF of Fe0.60Mn0.10-hexacyanoferrate (referred to as Fe0.60Mn0.10-HCF), with the chemical formula Na1.156Fe0.599Mn0.095Ni0.092Cu0.109Zn0.105 [Fe(CN)6]0.724·3.11H2O, displays the most appealing electrochemical performance of an ICE of 100%, a specific capacity of around 115 and 90 mAh·g-1 at 0.1 and 1.0 A·g-1, with 66.7% capacity retention observed after 1000 cycles and around 61.4% capacity retention with a 40-fold increase in specific current. We expect that our findings could provide reference strategies for the design of SIB cathode materials with superior electrochemical performance.
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Foodborne contaminants refer to substances that are present in food and threaten food safety. Due to the progress in detection technology and the rising concerns regarding public health, there has been a surge in research focusing on the dangers posed by foodborne contaminants. These studies aim to explore and implement strategies that are both safe and efficient in mitigating the associated risks. Anthocyanins, a class of flavonoids, are abundantly present in various plant species, such as blueberries, grapes, purple sweet potatoes, cherries, mulberries, and others. Numerous epidemiological and nutritional intervention studies have provided evidence indicating that the consumption of anthocyanins through dietary intake offers a range of protective effects against the detrimental impact of foodborne contaminants. The present study aims to differentiate between two distinct subclasses of foodborne contaminants: those that are generated during the processing of food and those that originate from the surrounding environment. Furthermore, the impact of anthocyanins on foodborne contaminants was also summarized based on a review of articles published within the last 10 years. However, further investigation is warranted regarding the mechanism by which anthocyanins target foodborne contaminants, as well as the potential impact of individual variations in response. Additionally, it is important to note that there is currently a dearth of clinical research examining the efficacy of anthocyanins as an intervention for mitigating the effects of foodborne pollutants. Thus, by exploring the detoxification effect and mechanism of anthocyanins on foodborne pollutants, this review thereby provides evidence, supporting the utilization of anthocyanin-rich diets as a means to mitigate the detrimental effects of foodborne contaminants.
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Antocianinas , Poluentes Ambientais , Antocianinas/farmacologia , Dieta , Inocuidade dos Alimentos , FrutasRESUMO
Objective: The aims of this study were to examine the effect of SARS-CoV-2 infection on cardiorespiratory fitness (CRF) and time-trial performance in vaccinated well-trained young kayak athletes. Methods: This is a longitudinal observational study. Sixteen (7 male, 9 female) vaccinated kayakers underwent body composition assessment, maximal graded exercise test, and 1000-m time-trial tests 21.9 ± 1.7 days before and 66.0 ± 2.2 days after the SARS-CoV-2 infection. The perception of training load was quantified with Borg's CR-10 scale before and after the infection return to sport period. Results: There were significant decreases in peak oxygen uptake (-9.7 %; effect size [ES] = 1.38), peak oxygen pulse (-5.7 %; ES = 0.96), and peak heart rate (-1.9 %; ES = 0.61). Peak minute ventilation, and minute ventilation/carbon dioxide production slope were unchanged after infection compared to the pre-infection values. In the entire 1000-m, the impaired tendencies were found in completion time, mean power, and mean speed (-2.4 to 1.2 %; small ESs = -0.40 to 0.47) as well as significant changes in stroke rate and stroke length (-4.5 to 3.7 %; ESs = -0.60 to 0.73). Conclusion: SARS-CoV-2 infection decreased CRF and time-trial performance even two months after return to regular training in vaccinated athletes.