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Superlattices-a periodic stacking of two-dimensional layers of two or more materials-provide a versatile scheme for engineering materials with tailored properties1,2. Here we report an intrinsic heterodimensional superlattice consisting of alternating layers of two-dimensional vanadium disulfide (VS2) and a one-dimensional vanadium sulfide (VS) chain array, deposited directly by chemical vapour deposition. This unique superlattice features an unconventional 1T stacking with a monoclinic unit cell of VS2/VS layers identified by scanning transmission electron microscopy. An unexpected Hall effect, persisting up to 380 kelvin, is observed when the magnetic field is in-plane, a condition under which the Hall effect usually vanishes. The observation of this effect is supported by theoretical calculations, and can be attributed to an unconventional anomalous Hall effect owing to an out-of-plane Berry curvature induced by an in-plane magnetic field, which is related to the one-dimensional VS chain. Our work expands the conventional understanding of superlattices and will stimulate the synthesis of more extraordinary superstructures.
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ABCG2, a member of the ABC transporter superfamily, is overexpressed in many human tumors and has long been studied for its ability to export a variety of chemotherapeutic agents, thereby conferring a multidrug resistance (MDR) phenotype. However, several studies have shown that ABCG2 can also confer an MDR-independent survival advantage to tumor cells exposed to stress. While investigating the mechanism by which ABCG2 enhances survival in stressful milieus, we have identified a physical and functional interaction between ABCG2 and SLC1A5, a member of the solute transporter superfamily and the primary transporter of glutamine in cancer cells. This interaction was accompanied by increased glutamine uptake, increased glutaminolysis, and rewired cellular metabolism, as evidenced by an increase in key metabolic enzymes and alteration of glutamine-dependent metabolic pathways. Specifically, we observed an increase in glutamine metabolites shuttled to the TCA cycle, and an increase in the synthesis of glutathione, accompanied by a decrease in basal levels of reactive oxygen species and a marked increase in cell survival in the face of oxidative stress. Notably, the knockdown of SLC1A5 or depletion of exogenous glutamine diminished ABCG2-enhanced autophagy flux, further implicating this solute transporter in ABCG2-mediated cell survival. This is, to our knowledge, the first report of a functionally significant physical interaction between members of the two major transporter superfamilies. Moreover, these observations may underlie the protective role of ABCG2 in cancer cells under duress and suggest a novel role for ABCG2 in the regulation of metabolism in normal and diseased states.
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Sobrevivência Celular , Glutamina , Antígenos de Histocompatibilidade Menor , Proteínas de Neoplasias , Estresse Oxidativo , Humanos , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Glutamina/metabolismo , Antígenos de Histocompatibilidade Menor/metabolismo , Antígenos de Histocompatibilidade Menor/genética , Transportador 1 de Aminoácido Excitatório/metabolismo , Transportador 1 de Aminoácido Excitatório/genética , Linhagem Celular Tumoral , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/genética , Espécies Reativas de Oxigênio/metabolismo , Sistema ASC de Transporte de AminoácidosRESUMO
The α7 nicotinic acetylcholine receptor (α7nAChR) plays a crucial role in the cholinergic anti-inflammatory pathway (CAP) during sepsis-associated acute lung injury (ALI). Increasing evidence suggests that specialized pro-resolving mediators (SPMs) are important in resolving α7nAChR-mediated ALI resolution. Our study aims to elucidate the pivotal role of α7nAChR in the CAP during LPS-associated acute lung injury (ALI). By employing vagus nerve stimulation (VNS), we identified α7nAChR as the key CAP subunit in ALI mice, effectively reducing lung permeability and the release of inflammatory cytokines. We further investigated the alterations in SPMs regulated by α7nAChR, revealing a predominant synthesis of lipoxin A4 (LXA4). The significance of α7nAChR-netrin-1 pathway in governing SPM synthesis was confirmed through the use of netrin-1 knockout mice and siRNA-transfected macrophages. Additionally, our evaluation identified a synchronous alteration of LXA4 synthesis in the α7nAChR-netrin-1 pathway accompanied by 5-lipoxygenase (5-LOX), thereby confirming an ameliorative effect of LXA4 on lung injury and macrophage inflammatory response. Concurrently, inhibiting the function of LXA4 annulled the lung-protective effect of VNS. As a result, our findings reveal a novel anti-inflammatory pathway wherein VNS modulates netrin-1 expression via α7nAChR, ultimately leading to LXA4 synthesis and subsequent lung protection.
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Lesão Pulmonar Aguda , Estimulação do Nervo Vago , Camundongos , Animais , Receptor Nicotínico de Acetilcolina alfa7/genética , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Lipopolissacarídeos/toxicidade , Netrina-1/metabolismo , Lesão Pulmonar Aguda/induzido quimicamenteRESUMO
Revealing the effect of surface structure changes on the electrocatalytic performance is beneficial to the development of highly efficient catalysts. However, precise regulation of the catalyst surface at the atomic level remains challenging. Here, we present a continuous strain regulation of palladium (Pd) on gold (Au) via a mechanically controllable surface strain (MCSS) setup. It is found that the structural changes induced by the strain setup can accelerate electron transfer at the solid-liquid interface, thus achieving a significantly improved performance toward hydrogen evolution reaction (HER). In situ X-ray diffraction (XRD) experiments further confirm that the enhanced activity is attributed to the increased interplanar spacing resulting from the applied strain. Theoretical calculations reveal that the tensile strain modulates the electronic structure of the Pd active sites and facilitates the desorption of the hydrogen intermediates. This work provides an effective approach for revealing the relationships between the electrocatalyst surface structure and catalytic activity.
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Metallene materials with atomic thicknesses are receiving increasing attention in electrocatalysis due to ultrahigh surface areas and distinctive surface strain. However, the continuous strain regulation of metallene remains a grand challenge. Herein, taking advantage of autocatalytic reduction of Cu2+ on biaxially strained, carbon-intercalated Ir metallene, we achieve control over the carbon extraction kinetics, enabling fine regulation of carbon intercalation concentration and continuous tuning of (111) in-plane (-2.0%-2.6%) and interplanar (3.5%-8.8%) strains over unprecedentedly wide ranges. Electrocatalysis measurements reveal the strain-dependent activity toward hydrogen evolution reaction (HER), where weakly strained Ir metallene (w-Ir metallene) with the smallest lattice constant presents the highest mass activity of 2.89 A mg-1Ir at -0.02 V vs reversible hydrogen electrode (RHE). Theoretical calculations validated the pivotal role of lattice compression in optimizing H binding on carbon-intercalated Ir metallene surfaces by downshifting the d-band center, further highlighting the significance of strain engineering for boosted electrocatalysis.
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BACKGROUND: Zingiber officinale Roscoe, colloquially known as ginger, is a crop of significant medicinal and culinary value that frequently encounters adversity stemming from inhospitable environmental conditions. The MYB transcription factors have garnered recognition for their pivotal role in orchestrating a multitude of plant biological pathways. Nevertheless, the enumeration and characterization of the MYBs within Z. officinale Roscoe remains unknown. This study embarks on a genome-wide scrutiny of the MYB gene lineage in ginger, with the aim of cataloging all ZoMYB genes implicated in the biosynthesis of gingerols and curcuminoids, and elucidating their potential regulatory mechanisms in counteracting abiotic stress, thereby influencing ginger growth and development. RESULTS: In this study, we identified an MYB gene family comprising 231 members in ginger genome. This ensemble comprises 74 singular-repeat MYBs (1R-MYB), 156 double-repeat MYBs (R2R3-MYB), and a solitary triple-repeat MYB (R1R2R3-MYB). Moreover, a comprehensive analysis encompassing the sequence features, conserved protein motifs, phylogenetic relationships, chromosome location, and gene duplication events of the ZoMYBs was conducted. We classified ZoMYBs into 37 groups, congruent with the number of conserved domains and gene structure analysis. Additionally, the expression profiles of ZoMYBs during development and under various stresses, including ABA, cold, drought, heat, and salt, were investigated in ginger utilizing both RNA-seq data and qRT-PCR analysis. CONCLUSION: This work provides a comprehensive understanding of the MYB family in ginger and lays the foundation for the future investigation of the potential functions of ZoMYB genes in ginger growth, development and abiotic stress tolerance of ginger.
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Família Multigênica , Filogenia , Proteínas de Plantas , Estresse Fisiológico , Fatores de Transcrição , Zingiber officinale , Zingiber officinale/genética , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: Bread wheat (Triticum aestivum L.) endosperm contains starch and proteins, which determine the final yield, quality, and nutritional value of wheat grain. The preferentially expressed endosperm genes can precisely provide targets in the endosperm for improving wheat grain quality and nutrition using modern bioengineering technologies. However, the genes specifically expressed in developing endosperms remain largely unknown. RESULTS: In this study, 315 preferentially expressed endosperm genes (PEEGs) in the spring wheat landrace, Chinese Spring, were screened using data obtained from an open bioinformatics database, which reveals a unique grain reserve deposition process and special signal transduction in a developing wheat endosperm. Furthermore, transcription and accumulation of storage proteins in the wheat cultivar, XC26 were evaluated. The results revealed that 315 PEEG plays a critical role in storage protein fragment deposition and is a potential candidate for modifying grain quality and nutrition. CONCLUSION: These results provide new insights into endosperm development and candidate genes and promoters for improving wheat grain quality through genetic engineering and plant breeding techniques.
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Grão Comestível , Endosperma , Regulação da Expressão Gênica de Plantas , Triticum , Triticum/genética , Triticum/metabolismo , Triticum/crescimento & desenvolvimento , Endosperma/genética , Endosperma/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Grão Comestível/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genes de Plantas , Perfilação da Expressão GênicaRESUMO
BACKGROUNDS: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer. METHODS: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest. RESULTS: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, Pâ <â .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, Pâ <â .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, Pâ =â .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, Pâ =â 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, Pâ <â .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, Pâ <â .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, Pâ <â .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, Pâ <â .05). CONCLUSION: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.
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Osteoarthritis (OA) is a common chronic inflammatory degenerative disease. Since chondrocytes are the only type of cells in cartilage, their survival is critical for maintaining cartilage morphology. This review offers a comprehensive analysis of how reactive oxygen species (ROS), including superoxide anions, hydrogen peroxide, hydroxyl radicals, nitric oxide, and their derivatives, affect cartilage homeostasis and trigger several novel modes of regulated cell death, including ferroptosis, parthanatos, and oxeiptosis, which may play roles in chondrocyte death and OA development. Moreover, we discuss potential therapeutic strategies to alleviate OA by scavenging ROS and provide new insight into the research and treatment of the role of regulated cell death in OA.
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Ferroptose , Osteoartrite , Parthanatos , Humanos , Condrócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Osteoartrite/metabolismoRESUMO
Efficient transceivers and antennas at terahertz frequencies are leading the development of 6G terahertz communication systems. The antenna design for high-resolution terahertz spatial sensing and communication remains challenging, while emergent metallic metasurface antennas can address this issue but often suffer from low efficiency and complex manufacturing. Here, an all-dielectric integrated meta-antenna operating in 6G terahertz communication window for high-efficiency beam focusing in the sub-wavelength scale is reported. With the antenna surface functionalized by metagrating arrays with asymmetric scattering patterns, the design and optimization methods are demonstrated with a physical size constraint. The highest manipulation and diffraction efficiencies achieve 84.1% and 48.1%. The commercially accessible fabrication method with low cost and easy to implement has been demonstrated for the meta-antenna by photocuring 3D printing. A filamentous focal spot is measured as 0.86λ with a long depth of focus of 25.3λ. Its application for integrated imaging and communication has been demonstrated. The proposed technical roadmap provides a general pathway for creating high-efficiency integrated meta-antennas with great potential in high-resolution 6G terahertz spatial sensing and communication applications.
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Conductance quantization of 2D materials is significant for understanding the charge transport at the atomic scale, which provides a platform to manipulate the quantum states, showing promising applications for nanoelectronics and memristors. However, the conventional methods for investigating conductance quantization are only applicable to materials consisting of one element, such as metal and graphene. The experimental observation of conductance quantization in transition metal dichalcogenides (TMDCs) with complex compositions and structures remains a challenge. To address this issue, an approach is proposed to characterize the charge transport across a single atom in TMDCs by integrating in situ synthesized 1T'-WTe2 electrodes with scanning tunneling microscope break junction (STM-BJ) technique. The quantized conductance of 1T'-WTe2 is measured for the first time, and the quantum states can be modulated by stretching speed and solvent. Combined with theoretical calculations, the evolution of quantized and corresponding configurations during the break junction process is demonstrated. This work provides a facile and reliable avenue to characterize and modulate conductance quantization of 2D materials, intensively expanding the research scope of quantum effects in diverse materials.
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The molecule-electrode coupling plays an essential role in photoresponsive devices with photochromic molecules, and the strong coupling between the molecule and the conventional electrodes leads to/ the quenching effect and limits the reversibility of molecular photoswitches. In this work, we developed a strategy of using transition metal dichalcogenides (TMDCs) electrodes to fabricate the thiol azobenzene (TAB) self-assembled monolayers (SAMs) junctions with the eutectic gallium-indium (EGaIn) technique. The current-voltage characteristics of the EGaIn/GaOx //TAB/TMDCs photoswitches showed an almost 100% reversible photoswitching behavior, which increased by â¼28% compared to EGaIn/GaOx //TAB/AuTS photoswitches. Density functional theory (DFT) calculations showed the coupling strength of the TAB-TMDCs electrode decreased by 42% compared to that of the TAB-AuTS electrode, giving rise to improved reversibility. our work demonstrated the feasibility of 2D TMDCs for fabricating SAMs-based photoswitches with unprecedentedly high reversibility.
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Experimental mapping of transmission is essential for understanding and controlling charge transport through molecular devices and materials. Here we developed a single-molecule photoelectron tunnelling spectroscopy approach for mapping transmission beyond the HOMO-LUMO gap of the single diketopyrrolopyrrole molecule junction using an ultrafast-laser combined scanning tunnelling microscope-based break junction set-up at room temperature. Two resonant transport channels of ultrafast photocurrent are found by our photoelectron tunnelling spectroscopy, ranging from 1.31 eV to 1.77 eV, consistent with the LUMO + 1 and LUMO + 2 in the transmission spectrum obtained by density functional theory calculations. Moreover, we observed the modulation of resonant peaks by varying bias voltages, which demonstrates the ability to quantitatively characterize the effect of the electric field on frontier molecular orbitals. Our single-molecule photoelectron tunnelling spectroscopy offers an avenue that allows us to explore the nature of energy-dependent charge transport through single-molecule junctions.
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Two-dimensional (2D) materials with multiphase, multielement crystals such as transition metal chalcogenides (TMCs) (based on V, Cr, Mn, Fe, Cd, Pt and Pd) and transition metal phosphorous chalcogenides (TMPCs) offer a unique platform to explore novel physical phenomena. However, the synthesis of a single-phase/single-composition crystal of these 2D materials via chemical vapour deposition is still challenging. Here we unravel a competitive-chemical-reaction-based growth mechanism to manipulate the nucleation and growth rate. Based on the growth mechanism, 67 types of TMCs and TMPCs with a defined phase, controllable structure and tunable component can be realized. The ferromagnetism and superconductivity in FeXy can be tuned by the y value, such as superconductivity observed in FeX and ferromagnetism in FeS2 monolayers, demonstrating the high quality of as-grown 2D materials. This work paves the way for the multidisciplinary exploration of 2D TMPCs and TMCs with unique properties.
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Allene oxide cyclase (AOC) is a key enzyme in the biosynthesis of jasmonic acid (JA), which is involved in plant growth and development as well as adaptation to environmental stresses. We identified the cold- and pathogen-responsive AOC2 gene from Medicago sativa subsp. falcata (MfAOC2) and its homolog MtAOC2 from Medicago truncatula. Heterologous expression of MfAOC2 in M. truncatula enhanced cold tolerance and resistance to the fungal pathogen Rhizoctonia solani, with greater accumulation of JA and higher transcript levels of JA downstream genes than in wild-type plants. In contrast, mutation of MtAOC2 reduced cold tolerance and pathogen resistance, with less accumulation of JA and lower transcript levels of JA downstream genes in the aoc2 mutant than in wild-type plants. The aoc2 phenotype and low levels of cold-responsive C-repeat-binding factor (CBF) transcripts could be rescued by expressing MfAOC2 in aoc2 plants or exogenous application of methyl jasmonate. Compared with wild-type plants, higher levels of CBF transcripts were observed in lines expressing MfAOC2 but lower levels of CBF transcripts were observed in the aoc2 mutant under cold conditions; superoxide dismutase, catalase, and ascorbate-peroxidase activities as well as proline concentrations were higher in MfAOC2-expressing lines but lower in the aoc2 mutant. These results suggest that expression of MfAOC2 or MtAOC2 promotes biosynthesis of JA, which positively regulates expression of CBF genes and antioxidant defense under cold conditions and expression of JA downstream genes after pathogen infection, leading to greater cold tolerance and pathogen resistance.
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Ciclopentanos , Oxilipinas , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Fenótipo , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: Hepatic pedicle clamping (HPC) is frequently utilized during hepatectomy to reduce intraoperative bleeding and diminish the need for intraoperative blood transfusion (IBT). The long-term prognostic implications of HPC following hepatectomy for hepatocellular carcinoma (HCC) remain under debate. This study aims to elucidate the association between HPC and oncologic outcomes after HCC resection, stratified by whether IBT was administered. PATIENTS AND METHODS: Prospectively collected data on patients with HCC who underwent curative resection from a multicenter database was studied. Patients were stratified into two cohorts on the basis of whether IBT was administered. The impact of HPC on long-term overall survival (OS) and recurrence-free survival (RFS) between the two cohorts was assessed by univariable and multivariable Cox regression analyses. RESULTS: Of 3362 patients, 535 received IBT. In the IBT cohort, using or not using HPC showed no significant difference in OS and RFS outcomes (5-year OS and RFS rates 27.9% vs. 24.6% and 13.8% vs. 12.0%, P = 0.810 and 0.530). However, in the non-IBT cohort of 2827 patients, the HPC subgroup demonstrated significantly decreased OS (5-year 45.9% vs. 56.5%, P < 0.001) and RFS (5-year 24.7% vs. 33.3%, P < 0.001) when compared with the subgroup without HPC. Multivariable Cox regression analysis identified HPC as an independent risk factor of OS and RFS [hazard ratios (HR) 1.16 and 1.12, P = 0.024 and 0.044, respectively] among patients who did not receive IBT. CONCLUSIONS: The impact of HPC on the oncological outcomes following hepatectomy for patients with HCC differed significantly whether IBT was administered, and HPC adversely impacted on long-term survival for patients without receiving IBT during hepatectomy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Constrição , Estudos Retrospectivos , Prognóstico , Transfusão de SangueRESUMO
In the cross-plane single-molecule junctions, the correlation between molecular aromaticity and conductance remained puzzling. Cross-plane break junction (XPBJ) provides new insight into understanding the role of aromaticity and conjugation to molecules on charge transport through the planar molecules. In this work, we investigated the modulation of cross-plane charge transport in pyrene derivatives by hydrogenation and substituents based on the XPBJ method that differs from those used in-plane transport. We measured the electrical conductance of the hydrogenated derivatives of the pyrenes and found that hydrogenation reduces conductance, and the fully hydrogenated molecule has the lowest conductance. Conductance of pyrene derivatives increased after substitution by both electron-donating and electron-withdrawing groups. By calculating, the trend in decreased conductance of hydrogenated pyrene was found to be consistent with the change in aromaticity. Electron-withdrawing substituents reduce the aromaticity of the molecule and narrow the HOMO-LUMO gap, while electron-donating groups increase the aromaticity but also narrow the gap. Our work reveals the potential of fine-tuning the structure of the pyrene molecule to control the cross-plane charge transport through the single-molecule junctions.
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Prussian blue analogues (PBAs) have advantages such as high voltage and low cost, making them one kind of the promising positive electrode materials for sodium-ion batteries. Particle dispersion is a key physical parameter of electrode materials, and understanding its impact on electrochemical performance is a prerequisite for obtaining high-performance PBAs. In this article, two PBAs samples with different particle dispersion were synthesized through sodium citrate-assisted co-precipitation method by means of staying and stirring. The influence of particle dispersion on electrochemical performance was investigated through polarization curve and AC impedance tests. It was found that PBAs with well-dispersed particles exhibited excellent rate performance, with a capacity of ~120â mAh g-1 at 1â C rate and a capacity retention of 75 % after 100 cycles. The capacity retention rate could reach 63 % at 5â C rate, far higher than that of PBAs samples with poor particle dispersion. From the perspective of electrochemical kinetics analysis, it has been shown that PBAs with well-dispersed particles exhibit smaller electrochemical polarization and faster Na+ diffusion reaction kinetics, which are key factors in achieving excellent rate performance.
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BACKGROUND: Immunogenic cell death (ICD) is a type of regulated cell death that plays a crucial role in activating the immune system in response to various stressors, including cancer cells and pathogens. However, the involvement of ICD in the human immune response against malaria remains to be defined. METHODS: In this study, data from Plasmodium falciparum infection cohorts, derived from cross-sectional studies, were analysed to identify ICD subtypes and their correlation with parasitaemia and immune responses. Using consensus clustering, ICD subtypes were identified, and their association with the immune landscape was assessed by employing ssGSEA. Differentially expressed genes (DEGs) analysis, functional enrichment, protein-protein interaction networks, and machine learning (least absolute shrinkage and selection operator (LASSO) regression and random forest) were used to identify ICD-associated hub genes linked with high parasitaemia. A nomogram visualizing these genes' correlation with parasitaemia levels was developed, and its performance was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In the P. falciparum infection cohort, two ICD-associated subtypes were identified, with subtype 1 showing better adaptive immune responses and lower parasitaemia compared to subtype 2. DEGs analysis revealed upregulation of proliferative signalling pathways, T-cell receptor signalling pathways and T-cell activation and differentiation in subtype 1, while subtype 2 exhibited elevated cytokine signalling and inflammatory responses. PPI network construction and machine learning identified CD3E and FCGR1A as candidate hub genes. A constructed nomogram integrating these genes demonstrated significant classification performance of high parasitaemia, which was evidenced by AUC values ranging from 0.695 to 0.737 in the training set and 0.911 to 0.933 and 0.759 to 0.849 in two validation sets, respectively. Additionally, significant correlations between the expressions of these genes and the clinical manifestation of P. falciparum infection were observed. CONCLUSION: This study reveals the existence of two ICD subtypes in the human immune response against P. falciparum infection. Two ICD-associated candidate hub genes were identified, and a nomogram was constructed for the classification of high parasitaemia. This study can deepen the understanding of the human immune response to P. falciparum infection and provide new targets for the prevention and control of malaria.
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Morte Celular Imunogênica , Malária Falciparum , Humanos , Relevância Clínica , Plasmodium falciparum/genética , Estudos Transversais , Malária Falciparum/genética , Biologia Computacional , Aprendizado de MáquinaRESUMO
6-methoxybenzoxazolinone (6-MBOA) is a secondary plant metabolite predominantly found in monocotyledonous plants, especially Gramineae. In damaged tissue, 2-ß-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-Glc) is hydrolyzed to DIMBOA, which spontaneously decomposes into 6-MBOA. It is commonly detected in plants consumed by voles and livestock and can also be present in cereal-based products. Discovered in 1955, this compound is renowned for its ability to trigger animal reproduction. However, there is a lack of research on its functional and mechanistic properties, leaving much of their potential unexplored. This review aimed to comprehensively summarize the effects of 6-MBOA on animal reproduction and human health, as well as its defensive role against herbivores. Studies have shown that 6-MBOA effectively inhibits the digestion, development, growth, and reproduction of insects. 6-MBOA may act as a partial agonist of melatonin and exert a regulatory role in mammalian reproduction, resulting in either promoting or inhibiting effects. 6-MBOA has been theorized to possess anti-tumor, anti-AIDS, anti-anxiety, and weight-loss effects in humans. However, insufficient attention has been paid to its defense properties against mammalian herbivores, and the mechanisms underlying its effects on mammalian reproduction remain unclear. In addition, research on its impact on human health is still in its preliminary stages. The review emphasizes the need for further systematic and comprehensive research on 6-MBOA to fully understand its diverse functions. Elucidating the effects of 6-MBOA on animal reproduction, adaptation, and human health would advance our understanding of plant-herbivore coevolution and the influence of environmental factors on animal population dynamics. Furthermore, this knowledge could potentially promote its application in human health and animal husbandry.