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Moiré superlattices have led to observations of exotic emergent electronic properties such as superconductivity and strong correlated states in small-rotation-angle twisted bilayer graphene (tBLG)1,2. Recently, these findings have inspired the search for new properties in moiré plasmons. Although plasmon propagation in the tBLG basal plane has been studied by near-field nano-imaging techniques3-7, the general electromagnetic character and properties of these plasmons remain elusive. Here we report the direct observation of two new plasmon modes in macroscopic tBLG with a highly ordered moiré superlattice. Using spiral structured nanoribbons of tBLG, we identify signatures of chiral plasmons that arise owing to the uncompensated Berry flux of the electron gas under optical pumping. The salient features of these chiral plasmons are shown through their dependence on optical pumping intensity and electron fillings, in conjunction with distinct resonance splitting and Faraday rotation coinciding with the spectral window of maximal Berry flux. Moreover, we also identify a slow plasmonic mode around 0.4 electronvolts, which stems from the interband transitions between the nested subbands in lattice-relaxed AB-stacked domains. This mode may open up opportunities for strong light-matter interactions within the highly sought after mid-wave infrared spectral window8. Our results unveil the new electromagnetic dynamics of small-angle tBLG and exemplify it as a unique quantum optical platform.
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Molecular recognition1-4 and supramolecular assembly5-8 cover a broad spectrum9-11 of non-covalently orchestrated phenomena between molecules. Catalysis12 of such processes, however, unlike that for the formation of covalent bonds, is limited to approaches13-16 that rely on sophisticated catalyst design. Here we establish a simple and versatile strategy to facilitate molecular recognition by extending electron catalysis17, which is widely applied18-21 in synthetic covalent chemistry, into the realm of supramolecular non-covalent chemistry. As a proof of principle, we show that the formation of a trisradical complex22 between a macrocyclic host and a dumbbell-shaped guest-a molecular recognition process that is kinetically forbidden under ambient conditions-can be accelerated substantially on the addition of catalytic amounts of a chemical electron source. It is, therefore, electrochemically possible to control23 the molecular recognition temporally and produce a nearly arbitrary molar ratio between the substrates and complexes ranging between zero and the equilibrium value. Such kinetically stable supramolecular systems24 are difficult to obtain precisely by other means. The use of the electron as a catalyst in molecular recognition will inspire chemists and biologists to explore strategies that can be used to fine-tune non-covalent events, control assembly at different length scales25-27 and ultimately create new forms of complex matter28-30.
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When faced with starvation, the bacterium Bacillus subtilis transforms itself into a dormant cell type called a "spore". Sporulation initiates with an asymmetric division event, which requires the relocation of the core divisome components FtsA and FtsZ, after which the sigma factor σF is exclusively activated in the smaller daughter cell. Compartment-specific activation of σF requires the SpoIIE phosphatase, which displays a biased localization on one side of the asymmetric division septum and associates with the structural protein DivIVA, but the mechanism by which this preferential localization is achieved is unclear. Here, we isolated a variant of DivIVA that indiscriminately activates σF in both daughter cells due to promiscuous localization of SpoIIE, which was corrected by overproduction of FtsA and FtsZ. We propose that the core components of the redeployed cell division machinery drive the asymmetric localization of DivIVA and SpoIIE to trigger the initiation of the sporulation program.
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Bacillus subtilis , Proteínas Bacterianas , Bacillus subtilis/metabolismo , Activación Transcripcional , Proteínas Bacterianas/metabolismo , Esporas Bacterianas/genética , Esporas Bacterianas/metabolismo , División Celular/genética , Factor sigma/genética , Factor sigma/metabolismoRESUMEN
We present Richardson-Lucy network (RLN), a fast and lightweight deep learning method for three-dimensional fluorescence microscopy deconvolution. RLN combines the traditional Richardson-Lucy iteration with a fully convolutional network structure, establishing a connection to the image formation process and thereby improving network performance. Containing only roughly 16,000 parameters, RLN enables four- to 50-fold faster processing than purely data-driven networks with many more parameters. By visual and quantitative analysis, we show that RLN provides better deconvolution, better generalizability and fewer artifacts than other networks, especially along the axial dimension. RLN outperforms classic Richardson-Lucy deconvolution on volumes contaminated with severe out of focus fluorescence or noise and provides four- to sixfold faster reconstructions of large, cleared-tissue datasets than classic multi-view pipelines. We demonstrate RLN's performance on cells, tissues and embryos imaged with widefield-, light-sheet-, confocal- and super-resolution microscopy.
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Algoritmos , Aprendizaje Profundo , Artefactos , Microscopía Fluorescente , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
BACKGROUND: Senescence is a series of degenerative changes in the structure and physiological function of an organism. Whether JPX (just proximal to XIST)-a newly identified age-related noncoding RNA by us-is associated with atherosclerosis is still unknown. Our study was to investigate the role of JPX and provide insights into potential therapies targeting atherosclerosis. METHODS: We analyzed clinical data from multiple tissues including meniscus tissue, leukemia cells, and peripheral blood monocytes to identify age-related noncoding RNAs in senescent vascular smooth muscle cells (VSMCs). The molecular mechanism of JPX was investigated by capture hybridization analysis of RNA targets and chromatin immunoprecipitation. IGVTools and real-time quantitative polymerase chain reaction were used to evaluate the JPX expression during phenotype regulation in age-related disease models. The therapeutic potential of JPX was evaluated after establishing an atherosclerosis model in smooth muscle-specific Jpx knockout mice. RESULTS: JPX expression was upregulated in activated ras allele (H-rasV12)-induced senescent VSMCs and atherosclerotic arteries. JPX knockdown substantially reduced the elevation of senescence-associated secretory phenotype (SASP) genes in senescent VSMCs. Cytoplasmic DNA leaked from mitochondria via mitochondrial permeability transition pore formed by VDAC1 (voltage-dependent anion channel 1) oligomer activates the STING (stimulator of interferon gene) pathway. JPX could act as an enhancer for the SASP genes and functions as a scaffold molecule through interacting with phosphorylated p65/RelA and BRD4 (bromodomain-containing protein 4) in chromatin remodeling complex, promoting the transcription of SASP genes via epigenetic regulation. Smooth muscle knockout of Jpx in ApoeKO mice resulted in a decrease in plaque area, a reduction in SASP gene expression, and a decrease in senescence compared with controls. CONCLUSIONS: As an enhancer RNA, JPX can integrate p65 and BRD4 to form a chromatin remodeling complex, activating SASP gene transcription and promoting cellular senescence. These findings suggest that JPX is a potential therapeutic target for the treatment of age-related atherosclerosis.
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Aterosclerosis , ARN Largo no Codificante , Ratones , Animales , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Músculo Liso Vascular/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Cromatina , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Epigénesis Genética , Aterosclerosis/genética , Aterosclerosis/metabolismo , Senescencia Celular/genética , Ratones Noqueados , Miocitos del Músculo Liso/metabolismoRESUMEN
Although catenanes comprising two ring-shaped components can be made in large quantities by templation, the preparation of three-dimensional (3D) catenanes with cage-shaped components is still in its infancy. Here, we report the design and syntheses of two 3D catenanes by a sequence of SN2 reactions in one pot. The resulting triply mechanically interlocked molecules were fully characterized in both the solution and solid states. Mechanistic studies have revealed that a suit[3]ane, which contains a threefold symmetric cage component as the suit and a tribromide component as the body, is formed at elevated temperatures. This suit[3]ane was identified as the key reactive intermediate for the selective formation of the two 3D catenanes which do not represent thermodynamic minima. We foresee a future in which this particular synthetic strategy guides the rational design and production of mechanically interlocked molecules under kinetic control.
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Catenanos , Rotaxanos , Catenanos/química , Cinética , Rotaxanos/químicaRESUMEN
BACKGROUND AND AIMS: Vascular smooth muscle cell (VSMC) senescence is crucial for the development of atherosclerosis, characterized by metabolic abnormalities. Tumour necrosis factor receptor-associated protein 1 (TRAP1), a metabolic regulator associated with ageing, might be implicated in atherosclerosis. As the role of TRAP1 in atherosclerosis remains elusive, this study aimed to examine the function of TRAP1 in VSMC senescence and atherosclerosis. METHODS: TRAP1 expression was measured in the aortic tissues of patients and mice with atherosclerosis using western blot and RT-qPCR. Senescent VSMC models were established by oncogenic Ras, and cellular senescence was evaluated by measuring senescence-associated ß-galactosidase expression and other senescence markers. Chromatin immunoprecipitation (ChIP) analysis was performed to explore the potential role of TRAP1 in atherosclerosis. RESULTS: VSMC-specific TRAP1 deficiency mitigated VSMC senescence and atherosclerosis via metabolic reprogramming. Mechanistically, TRAP1 significantly increased aerobic glycolysis, leading to elevated lactate production. Accumulated lactate promoted histone H4 lysine 12 lactylation (H4K12la) by down-regulating the unique histone lysine delactylase HDAC3. H4K12la was enriched in the senescence-associated secretory phenotype (SASP) promoter, activating SASP transcription and exacerbating VSMC senescence. In VSMC-specific Trap1 knockout ApoeKO mice (ApoeKOTrap1SMCKO), the plaque area, senescence markers, H4K12la, and SASP were reduced. Additionally, pharmacological inhibition and proteolysis-targeting chimera (PROTAC)-mediated TRAP1 degradation effectively attenuated atherosclerosis in vivo. CONCLUSIONS: This study reveals a novel mechanism by which mitonuclear communication orchestrates gene expression in VSMC senescence and atherosclerosis. TRAP1-mediated metabolic reprogramming increases lactate-dependent H4K12la via HDAC3, promoting SASP expression and offering a new therapeutic direction for VSMC senescence and atherosclerosis.
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The sequence-controlled assembly of nucleic acids and amino acids into well-defined superstructures constitutes one of the most revolutionary technologies in modern science. The elaboration of such superstructures from carbohydrates, however, remains elusive and largely unexplored on account of their intrinsic constitutional and configurational complexity, not to mention their inherent conformational flexibility. Here, we report the bottom-up assembly of two classes of hierarchical superstructures that are formed from a highly flexible cyclo-oligosaccharideânamely, cyclofructan-6 (CF-6). The formation of coordinative bonds between the oxygen atoms of CF-6 and alkali metal cations (i) locks a myriad of flexible conformations of CF-6 into a few rigid conformations, (ii) bridges adjacent CF-6 ligands, and (iii) gives rise to the multiple-level assembly of three extended frameworks. The hierarchical superstructures present in these frameworks have been shown to modulate their nanomechanical properties. This research highlights the unique opportunities of constructing convoluted superstructures from carbohydrates and should encourage future endeavors in this underinvestigated field of science.
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Carbohidratos , Metales , Metales/química , Carbohidratos/química , Conformación Molecular , AminoácidosRESUMEN
The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1 has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV-vis-NIR spectroscopies. The flexible 3D molecular architecture of GFN-1, along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1 exhibits strong binding affinities for fullerenes, leading to host-guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.
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Endothelial dysfunction is an initiating factor in atherosclerosis. Endothelial cells (ECs) are constantly subject to blood flow shear stress, and atherosclerotic plaques tend to occur in aortic bends or bifurcations impaired by low oscillatory shear stress (OSS). However, the mechanism that how OSS affects the initiation and progression of atherosclerosis remains to be explored. Here, we first reported that OSS can promote endothelial dysfunction and atherogenesis in vivo and in vitro by activating STING pathway. Mechanistically, at atherosclerosis-prone areas, OSS caused mitochondria damage in ECs, leading to the leakage of mitochondrial DNA (mtDNA) into the cytoplasm. The cytoplasmic mtDNA was recognized by cGAS to produce cGAMP, activating the STING pathway and leading to endothelial senescence, which resulted in endothelial dysfunction and atherosclerosis. We found that STING was activated in plaques of atherosclerotic patients and in aortic arch ECs of high-fat diet (HFD)-fed ApoeKO mice, as well as in ECs exposed to OSS. STING-specific deficiency in ECs attenuates endothelial senescence and resulted in a significant reduction in aortic arch plaque area in HFD-fed ApoeKO mice. Consistently, specific deficiency or pharmacological inhibition of STING attenuated OSS-induced senescence and endothelial dysfunction. Pharmacological depletion of mtDNA ameliorated OSS-induced senescence and endothelial dysfunction. Taken together, our study linked hemodynamics and endothelial senescence, and revealed a novel mechanism by which OSS leads to endothelial dysfunction. Our study provided new insights into the development of therapeutic strategies for endothelial senescence and atherosclerosis.
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Aterosclerosis , Senescencia Celular , Células Endoteliales , Proteínas de la Membrana , Estrés Mecánico , Animales , Humanos , Ratones , Aterosclerosis/metabolismo , Aterosclerosis/patología , Aterosclerosis/genética , Células Cultivadas , Senescencia Celular/genética , Dieta Alta en Grasa , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Mitocondrias/patologíaRESUMEN
The quality requirements of graphene depend on the applications. Some have a high tolerance for graphene quality and even require some defects, while others require graphene as perfect as possible to achieve good performance. So far, synthesis of large-area graphene films by chemical vapor deposition of carbon precursors on metal substrates, especially on Cu, remains the main way to produce high-quality graphene, which has been significantly developed in the past 15 years. However, although many prototypes are demonstrated, their performance is still more or less far from the theoretical property limit of graphene. This review focuses on how to make super graphene, namely graphene with a perfect structure and free of contaminations. More specially, this study focuses on graphene synthesis on Cu substrates. Typical defects in graphene are first discussed together with the formation mechanisms and how they are characterized normally, followed with a brief review of graphene properties and the effects of defects. Then, the synthesis progress of super graphene from the aspects of substrate, grain size, wrinkles, contamination, adlayers, and point defects are reviewed. Graphene transfer is briefly discussed as well. Finally, the challenges to make super graphene are discussed and a strategy is proposed.
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We demonstrate residual channel attention networks (RCAN) for the restoration and enhancement of volumetric time-lapse (four-dimensional) fluorescence microscopy data. First we modify RCAN to handle image volumes, showing that our network enables denoising competitive with three other state-of-the-art neural networks. We use RCAN to restore noisy four-dimensional super-resolution data, enabling image capture of over tens of thousands of images (thousands of volumes) without apparent photobleaching. Second, using simulations we show that RCAN enables resolution enhancement equivalent to, or better than, other networks. Third, we exploit RCAN for denoising and resolution improvement in confocal microscopy, enabling ~2.5-fold lateral resolution enhancement using stimulated emission depletion microscopy ground truth. Fourth, we develop methods to improve spatial resolution in structured illumination microscopy using expansion microscopy data as ground truth, achieving improvements of ~1.9-fold laterally and ~3.6-fold axially. Finally, we characterize the limits of denoising and resolution enhancement, suggesting practical benchmarks for evaluation and further enhancement of network performance.
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Microscopía Fluorescente/métodos , Algoritmos , Aprendizaje Profundo , Procesamiento de Imagen Asistido por ComputadorRESUMEN
Resting cells represent a survival strategy employed by diatoms to endure prolonged periods of unfavourable conditions. In the oceans, many diatoms sink at the end of their blooming season and therefore need to endure cold and dark conditions in the deeper layers of the water column. How they survive these conditions is largely unknown. We conducted an integrative analysis encompassing methods from histology, physiology, biochemistry, and genetics to reveal the biological mechanism of resting-cell formation in the model diatom Thalassiosira pseudonana. Resting-cell formation was triggered by a decrease in light and temperature with subsequent catabolism of storage compounds. Resting cells were characterised by an acidic and viscous cytoplasm and altered morphology of the chloroplast ultrastructure. The formation of resting cells in T. pseudonana is an energy demanding process required for a biophysical alteration of the cytosol and chloroplasts to endure the unfavourable conditions of the deeper ocean as photosynthetic organisms. However, most resting cells (> 90%) germinate upon return to favorable growth conditions.
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Cloroplastos , Diatomeas , Luz , Diatomeas/ultraestructura , Diatomeas/fisiología , Diatomeas/crecimiento & desarrollo , Cloroplastos/metabolismo , Cloroplastos/ultraestructura , Temperatura , Organismos Acuáticos , FotosíntesisRESUMEN
OBJECTIVE: This study aims to investigate the effect of lysine demethylase 5B (KDM5B)-mediated dimethyl-lysine 4 histone H3 (H3K4me2) demethylation on immune microenvironment remodeling in pancreatic cancer. METHODS: Pan 02 mouse pancreatic cancer cell lines were cultured and used to establish tumor model in vivo. RT-qPCR and Western blot were used to detect the expression of stimulator of interferon gene (STING) and KDM5B in pancreatic cancer tissues and Pan 02 cells. The specific demethylation domain of KDM5B was detected by isothermal titration calorimetry binding assay. The regulatory roles of KDM5B in cell apoptosis and remodeling of immune microenvironment in vitro and in vivo were explored after loss-of functions in KDM5B. RESULTS: KDM5B was highly expressed but STING was poorly expressed in pancreatic cancer tissues and Pan 02 cells. After knockdown of KDM5B, CD8+ T cells recognized and killed Pan 02 cells, which promoted the infiltration of CD8+ T cells in Pan 02 cells, thus improving the anti-tumor ability. The PHD domain in KDM5B specifically bound to H3K4me2 peptide and inhibition of KDM5B induced STING expression. Knockdown of KDM5B up-regulated STING expression to promote apoptosis, thus regulating the immune microenvironment and inhibiting the growth of tumor in mice. Meanwhile, knockdown of KDM5B and STING simultaneously counteracted the knockdown effect of KDM5B. CONCLUSION: Inhibition of KDM5B can promote the expression of STING through H3K4me2 demethylation, which promoted the recognition and killing of Pan 02 cells by CD8+ T cells, thus improving the anti-tumor ability and regulating the immune microenvironment.
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Linfocitos T CD8-positivos , Neoplasias Pancreáticas , Animales , Ratones , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Expresión Génica , Histonas/metabolismo , Lisina/metabolismo , Microambiente TumoralRESUMEN
This study aims to develop a prognostic signature based on m6A-related lncRNAs for clear cell renal cell carcinoma (ccRCC). Differential expression analysis and Pearson correlation analysis were used to identify m6A-related lncRNAs associated with patient outcomes in The Cancer Genome Atlas (TCGA) database. Our approach led to the development of an m6A-related lncRNA risk score (MRLrisk), formulated using six identified lncRNAs: NFE4, AL008729.2, AL139123.1, LINC02154, AC124854.1 and ARHGAP31-AS1. Higher MRLrisk was identified as a risk factor for patients' prognosis in ccRCC. Furthermore, an MRLrisk-based nomogram was developed and demonstrated as a reliable tool for prognosis prediction in ccRCC. Enrichment analysis and tumor mutation signature studies were conducted to investigate MRLrisk-related biological phenotypes. The tumor immune dysfunction and exclusion (TIDE) score was employed to infer patients' response to immunotherapy, indicating a negative correlation between high MRLrisk and immunotherapy response. Our focus then shifted to LINC02154 for deeper exploration. We assessed LINC02154 expression in 28 ccRCC/normal tissue pairs and 3 ccRCC cell lines through quantitative real-time polymerase chain reaction (qRT-PCR). Functional experiments, including EdU incorporation, flow cytometry and transwell assays, were performed to assess the role of LINC02154 in ccRCC cell functions, discovering that its downregulation hinders cancer cell proliferation and migration. Furthermore, the influence of LINC02154 on ccRCC cells' sensitivity to Sunitinib was explored using CCK-8 assays, demonstrating that decreased LINC02154 expression increases Sunitinib sensitivity. In summary, this study successfully developed an MRLrisk model with significant prognostic value for ccRCC and established LINC02154 as a critical biomarker and prospective therapeutic target in ccRCC management.
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Carcinoma de Células Renales , Neoplasias Renales , ARN Largo no Codificante , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , ARN Largo no Codificante/genética , Neoplasias Renales/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Pronóstico , Progresión de la Enfermedad , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Proliferación Celular/efectos de los fármacos , Biomarcadores de Tumor/genética , Sunitinib/uso terapéutico , Sunitinib/farmacología , Masculino , Femenino , Movimiento Celular/genética , Adenosina/análogos & derivadosRESUMEN
To meet the demand for higher energy density in lithium-ion batteries and expand their application range, coupling lithium metal anodes with high-voltage cathodes is an ideal solution. However, the compatibility between lithium metal batteries and electrolytes affects their applicability. In this study, proposes a locally concentrated electrolyte based on ethyl acetate (EA) as the solvent, lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) as the lithium salt, and lithium difluorooxoborate (LiDFOB) as a sacrificial agent to enhance the low-temperature and high-voltage endurance of Li//Lithium cobalt oxide (LCO) batteries. The Li//LCO battery can operate within the voltage range of 3 to 4.5â V, with an initial discharge specific capacity of 174.5â mAh g-1 at 20 °C. At -40 °C, after 200 cycles, the capacity retention rate is 87.7 %. It can operate under extreme conditions of -70 °C, with a discharge specific capacity of 112.6â mAh g-1. Additionally, LCO//HC batteries using this electrolyte demonstrate excellent performance. Present work provides a new perspective for the optimization of electrolytes for low-temperature lithium-ion batteries.
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Low temperature has been a major challenge for lithium-ion batteries (LIBs) to maintain satisfied electrochemical performance, and the main reason is the deactivation of electrolyte with the decreasing temperature. To address this point, in present work, we develop a low-temperature resistant electrolyte which includes ethyl acetate (EA) and fluoroethylene carbonate (FEC) as solvent and lithium difluoro(oxalato)borate (LiDFOB) as the primary lithium salt. Due to the preferential decomposition of LiDFOB and FEC, a solid electrolyte interface rich in LiF is formed on the lithium metal anodes (LMAs) and lithium cobalt oxide (LCO) cathodes, contributing to higher stability and rapid desolvation of Li+ ions. The batteries with the optimized electrolyte can undergo cycling tests at -40 °C, with a capacity retention of 83.9 % after 200 cycles. Furthermore, the optimized electrolyte exhibits excellent compatibility with both LCO cathodes and graphite (Gr) anodes, enabling a Gr/LCO battery to maintain a capacity retention of 90.3 % after multiple cycles at -25 °C. This work proposes a cost-effective electrolyte that can activate potential LIBs in practical scenarios, especially in low-temperature environments.
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In American men, the incidence of prostate cancer (PC) is the highest among all types of cancer, making it the second leading cause of mortality associated with cancer. For advanced or metastatic PC, antiandrogen therapies are standard treatment options. The administration of these treatments unfortunately carries the potential risk of inducing neuroendocrine prostate cancer (NEPC). Neuroendocrine differentiation (NED) serves as a crucial indicator of prostate cancer development, encompassing various factors such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), Yes-associated protein 1 (YAP1), AMP-activated protein kinase (AMPK), miRNA. The processes of autophagy and ferroptosis (an iron-dependent form of programmed cell death) play pivotal roles in the regulation of various types of cancers. Clinical trials and preclinical investigations have been conducted on many signaling pathways during the development of NEPC, with the deepening of research, autophagy and ferroptosis appear to be the potential target for regulating NEPC. Due to the dual nature of autophagy and ferroptosis in cancer, gaining a deeper understanding of the developmental programs associated with achieving autophagy and ferroptosis may enhance risk stratification and treatment efficacy for patients with NEPC.
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Autofagia , Ferroptosis , Neoplasias de la Próstata , Humanos , Ferroptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Animales , Transducción de Señal/efectos de los fármacos , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/metabolismoRESUMEN
Low temperature has been a major challenge for lithium-ion batteries to maintain satisfied electrochemical performance, as it leads to poor rechargeability and low capacity retention. Traditional carbonate solvents, vinyl carbonate and dimethyl carbonate are indispensable components of commercial electrolytes. However, the higher melting point of these carbonate solvents causes their electrical conductivity to be easily reduced when temperatures drop below zero, limiting their ability to facilitate lithium ion transport. In this work, we demonstrate that the use of methyl propionate (MP) carboxylate and fluorocarbonate vinyl (FEC) electrolytes can overcome the limitations of low temperature cycling. Compared with carbonate electrolyte, MP has the characteristics of low melting point, low viscosity and low binding energy with Li+, which is crucial to improve the low temperature performance of the battery, while FEC is an effective component to inhibit the side reaction between MP and lithium metal. The carefully formulated MP-based electrolyte can generate a solid electrolyte interface with low resistance and rich in inorganic substances, which is conducive to the smooth diffusion of Li+, allowing the battery to successfully cycle at a high rate of 0.5 C at -20 °C, and giving it a reversible capacity retention rate of 65.3% at -40oC. This work designs a promising advanced electrolyte and holds the potential to overcome limitations of lithium-ion batteries in harsh conditions.
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Individualized cortical network topography (ICNT) varies between people and exhibits great variability in the association networks in the human brain. However, these findings were mainly discovered in Western populations. It remains unclear whether and how ICNT is shaped by the non-Western populations. Here, we leveraged a multisession hierarchical Bayesian model to define individualized functional networks in White American and Han Chinese populations with data from both US and Chinese Human Connectome Projects. We found that both the size and spatial topography of individualized functional networks differed between White American and Han Chinese groups, especially in the heteromodal association cortex (including the ventral attention, control, language, dorsal attention, and default mode networks). Employing a support vector machine, we then demonstrated that ethnicity-related ICNT diversity can be used to identify an individual's ethnicity with high accuracy (74%, pperm < 0.0001), with heteromodal networks contributing most to the classification. This finding was further validated through mass-univariate analyses with generalized additive models. Moreover, we reveal that the spatial heterogeneity of ethnic diversity in ICNT correlated with fundamental properties of cortical organization, including evolutionary cortical expansion, brain myelination, and cerebral blood flow. Altogether, this case study highlights a need for more globally diverse and publicly available neuroimaging datasets.