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The enhancement of separation processes and electrochemical technologies such as water electrolysers1,2, fuel cells3,4, redox flow batteries5,6 and ion-capture electrodialysis7 depends on the development of low-resistance and high-selectivity ion-transport membranes. The transport of ions through these membranes depends on the overall energy barriers imposed by the collective interplay of pore architecture and pore-analyte interaction8,9. However, it remains challenging to design efficient, scaleable and low-cost selective ion-transport membranes that provide ion channels for low-energy-barrier transport. Here we pursue a strategy that allows the diffusion limit of ions in water to be approached for large-area, free-standing, synthetic membranes using covalently bonded polymer frameworks with rigidity-confined ion channels. The near-frictionless ion flow is synergistically fulfilled by robust micropore confinement and multi-interaction between ion and membrane, which afford, for instance, a Na+ diffusion coefficient of 1.18 × 10-9 m2 s-1, close to the value in pure water at infinite dilution, and an area-specific membrane resistance as low as 0.17 Ω cm2. We demonstrate highly efficient membranes in rapidly charging aqueous organic redox flow batteries that deliver both high energy efficiency and high-capacity utilization at extremely high current densities (up to 500 mA cm-2), and also that avoid crossover-induced capacity decay. This membrane design concept may be broadly applicable to membranes for a wide range of electrochemical devices and for precise molecular separation.
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Plasmas can generate ultra-high-temperature reactive environments that can be used for the synthesis and processing of a wide range of materials1,2. However, the limited volume, instability and non-uniformity of plasmas have made it challenging to scalably manufacture bulk, high-temperature materials3-8. Here we present a plasma set-up consisting of a pair of carbon-fibre-tip-enhanced electrodes that enable the generation of a uniform, ultra-high temperature and stable plasma (up to 8,000 K) at atmospheric pressure using a combination of vertically oriented long and short carbon fibres. The long carbon fibres initiate the plasma by micro-spark discharge at a low breakdown voltage, whereas the short carbon fibres coalesce the discharge into a volumetric and stable ultra-high-temperature plasma. As a proof of concept, we used this process to synthesize various extreme materials in seconds, including ultra-high-temperature ceramics (for example, hafnium carbonitride) and refractory metal alloys. Moreover, the carbon-fibre electrodes are highly flexible and can be shaped for various syntheses. This simple and practical plasma technology may help overcome the challenges in high-temperature synthesis and enable large-scale electrified plasma manufacturing powered by renewable electricity.
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The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality1. Although an increasing number of interventions show promise for rejuvenation2, their effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. Here we performed single-cell RNA sequencing on 20 organs to reveal cell-type-specific responses to young and aged blood in heterochronic parabiosis. Adipose mesenchymal stromal cells, haematopoietic stem cells and hepatocytes are among those cell types that are especially responsive. On the pathway level, young blood invokes new gene sets in addition to reversing established ageing patterns, with the global rescue of genes encoding electron transport chain subunits pinpointing a prominent role of mitochondrial function in parabiosis-mediated rejuvenation. We observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it in select cell types. Together, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity.
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Parabiosis , Análisis de la Célula Individual , Adipocitos , Envejecimiento/genética , Transporte de Electrón/genética , Células Madre Hematopoyéticas , Hepatocitos , Células Madre Mesenquimatosas , Mitocondrias , Especificidad de Órganos/genética , RNA-Seq , RejuvenecimientoRESUMEN
Compared with their three-dimensional (3D) counterparts, low-dimensional metal halide perovskites (2D and quasi-2D; B2An-1MnX3n+1, such as B = R-NH3+, A = HC(NH2)2+, Cs+; M = Pb2+, Sn2+; X = Cl-, Br-, I-) with periodic inorganic-organic structures have shown promising stability and hysteresis-free electrical performance1-6. However, their unique multiple-quantum-well structure limits the device efficiencies because of the grain boundaries and randomly oriented quantum wells in polycrystals7. In single crystals, the carrier transport through the thickness direction is hindered by the layered insulating organic spacers8. Furthermore, the strong quantum confinement from the organic spacers limits the generation and transport of free carriers9,10. Also, lead-free metal halide perovskites have been developed but their device performance is limited by their low crystallinity and structural instability11. Here we report a low-dimensional metal halide perovskite BA2MAn-1SnnI3n+1 (BA, butylammonium; MA, methylammonium; n = 1, 3, 5) superlattice by chemical epitaxy. The inorganic slabs are aligned vertical to the substrate and interconnected in a criss-cross 2D network parallel to the substrate, leading to efficient carrier transport in three dimensions. A lattice-mismatched substrate compresses the organic spacers, which weakens the quantum confinement. The performance of a superlattice solar cell has been certified under the quasi-steady state, showing a stable 12.36% photoelectric conversion efficiency. Moreover, an intraband exciton relaxation process may have yielded an unusually high open-circuit voltage (VOC).
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Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing1-3. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds4,5. We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.
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Envejecimiento , Encéfalo , Líquido Cefalorraquídeo , Células Precursoras de Oligodendrocitos , Oligodendroglía , Animales , Diferenciación Celular/genética , Líquido Cefalorraquídeo/fisiología , Factores de Crecimiento de Fibroblastos/metabolismo , Regulación de la Expresión Génica , Ratones , Células Precursoras de Oligodendrocitos/metabolismo , Oligodendroglía/metabolismoRESUMEN
The human brain vasculature is of great medical importance: its dysfunction causes disability and death1, and the specialized structure it forms-the blood-brain barrier-impedes the treatment of nearly all brain disorders2,3. Yet so far, we have no molecular map of the human brain vasculature. Here we develop vessel isolation and nuclei extraction for sequencing (VINE-seq) to profile the major vascular and perivascular cell types of the human brain through 143,793 single-nucleus transcriptomes from 25 hippocampus and cortex samples of 9 individuals with Alzheimer's disease and 8 individuals with no cognitive impairment. We identify brain-region- and species-enriched genes and pathways. We reveal molecular principles of human arteriovenous organization, recapitulating a gradual endothelial and punctuated mural cell continuum. We discover two subtypes of human pericytes, marked by solute transport and extracellular matrix (ECM) organization; and define perivascular versus meningeal fibroblast specialization. In Alzheimer's disease, we observe selective vulnerability of ECM-maintaining pericytes and gene expression patterns that implicate dysregulated blood flow. With an expanded survey of brain cell types, we find that 30 of the top 45 genes that have been linked to Alzheimer's disease risk by genome-wide association studies (GWASs) are expressed in the human brain vasculature, and we confirm this by immunostaining. Vascular GWAS genes map to endothelial protein transport, adaptive immune and ECM pathways. Many are microglia-specific in mice, suggesting a partial evolutionary transfer of Alzheimer's disease risk. Our work uncovers the molecular basis of the human brain vasculature, which will inform our understanding of overall brain health, disease and therapy.
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Enfermedad de Alzheimer , Encéfalo , Susceptibilidad a Enfermedades , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Animales , Encéfalo/irrigación sanguínea , Encéfalo/citología , Encéfalo/metabolismo , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Estudio de Asociación del Genoma Completo , Hipocampo/irrigación sanguínea , Hipocampo/citología , Hipocampo/metabolismo , Humanos , Ratones , Microglía/metabolismo , Pericitos/metabolismo , TranscriptomaRESUMEN
The vascular interface of the brain, known as the blood-brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability1-3. Yet, recent studies have demonstrated that brain ageing is sensitive to circulatory proteins4,5. Thus, it is unclear whether permeability to individually injected exogenous tracers-as is standard in BBB studies-fully represents blood-to-brain transport. Here we label hundreds of proteins constituting the mouse blood plasma proteome, and upon their systemic administration, study the BBB with its physiological ligand. We find that plasma proteins readily permeate the healthy brain parenchyma, with transport maintained by BBB-specific transcriptional programmes. Unlike IgG antibody, plasma protein uptake diminishes in the aged brain, driven by an age-related shift in transport from ligand-specific receptor-mediated to non-specific caveolar transcytosis. This age-related shift occurs alongside a specific loss of pericyte coverage. Pharmacological inhibition of the age-upregulated phosphatase ALPL, a predicted negative regulator of transport, enhances brain uptake of therapeutically relevant transferrin, transferrin receptor antibody and plasma. These findings reveal the extent of physiological protein transcytosis to the healthy brain, a mechanism of widespread BBB dysfunction with age and a strategy for enhanced drug delivery.
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Envejecimiento/metabolismo , Envejecimiento/patología , Barrera Hematoencefálica/metabolismo , Transcitosis , Fosfatasa Alcalina/metabolismo , Animales , Anticuerpos/metabolismo , Transporte Biológico , Proteínas Sanguíneas/administración & dosificación , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/farmacocinética , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Sistemas de Liberación de Medicamentos , Salud , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Plasma/metabolismo , Proteoma/administración & dosificación , Proteoma/metabolismo , Proteoma/farmacocinética , Receptores de Transferrina/inmunología , Transcripción Genética , Transferrina/metabolismoRESUMEN
Organic-inorganic hybrid perovskites have electronic and optoelectronic properties that make them appealing in many device applications1-4. Although many approaches focus on polycrystalline materials5-7, single-crystal hybrid perovskites show improved carrier transport and enhanced stability over their polycrystalline counterparts, due to their orientation-dependent transport behaviour8-10 and lower defect concentrations11,12. However, the fabrication of single-crystal hybrid perovskites, and controlling their morphology and composition, are challenging12. Here we report a solution-based lithography-assisted epitaxial-growth-and-transfer method for fabricating single-crystal hybrid perovskites on arbitrary substrates, with precise control of their thickness (from about 600 nanometres to about 100 micrometres), area (continuous thin films up to about 5.5 centimetres by 5.5 centimetres), and composition gradient in the thickness direction (for example, from methylammonium lead iodide, MAPbI3, to MAPb0.5Sn0.5I3). The transferred single-crystal hybrid perovskites are of comparable quality to those directly grown on epitaxial substrates, and are mechanically flexible depending on the thickness. Lead-tin gradient alloying allows the formation of a graded electronic bandgap, which increases the carrier mobility and impedes carrier recombination. Devices based on these single-crystal hybrid perovskites show not only high stability against various degradation factors but also good performance (for example, solar cells based on lead-tin-gradient structures with an average efficiency of 18.77 per cent).
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Hepatocellular carcinoma (HCC) is one of the most fatal malignancies. Early diagnosis of HCC is crucial in reducing the risk for mortality. This study analyzed a panel of nine fusion transcripts in serum samples from 61 patients with HCC and 75 patients with non-HCC conditions, using TaqMan real-time quantitative RT-PCR. Seven of the nine fusions frequently detected in patients with HCC included: MAN2A1-FER (100%), SLC45A2-AMACR (62.3%), ZMPSTE24-ZMYM4 (62.3%), PTEN-NOLC1 (57.4%), CCNH-C5orf30 (55.7%), STAMBPL1-FAS (26.2%), and PCMTD1-SNTG1 (16.4%). Machine-learning models were constructed based on serum fusion-gene levels to predict HCC in the training cohort, using the leave-one-out cross-validation approach. One machine-learning model, called the four fusion genes logistic regression model (MAN2A1-FER≤40, CCNH-C5orf30≤38, SLC45A2-AMACR≤41, and PTEN-NOLC1≤40), produced accuracies of 91.5% and 83.3% in the training and testing cohorts, respectively. When serum α-fetal protein level was incorporated into the machine-learning model, a two fusion gene (MAN2A1-FER≤40, CCNH-C5orf30≤38) + α-fetal protein logistic regression model was found to generate an accuracy of 94.8% in the training cohort. The same model resulted in 95% accuracy in both the testing and combined cohorts. Cancer treatment was associated with reduced levels of most of the serum fusion transcripts. Serum fusion-gene machine-learning models may serve as important tools in screening for HCC and in monitoring the impact of HCC treatment.
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Biomarcadores de Tumor , Carcinoma Hepatocelular , Neoplasias Hepáticas , Aprendizaje Automático , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/sangre , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Adulto , Proteínas de Fusión Oncogénica/genéticaRESUMEN
Cognitive and behavioral rigidity are observed in various psychiatric diseases, including in autism spectrum disorder (ASD). However, the underlying mechanism remains to be elucidated. In this study, we found that neuroligin-3 (NL3) R451C knockin mouse model of autism (KI mice) exhibited deficits in behavioral flexibility in choice selection tasks. Single-unit recording of medium spiny neuron (MSN) activity in the nucleus accumbens (NAc) revealed altered encoding of decision-related cue and impaired updating of choice anticipation in KI mice. Additionally, fiber photometry demonstrated significant disruption in dynamic mesolimbic dopamine (DA) signaling for reward prediction errors (RPEs), along with reduced activity in medial prefrontal cortex (mPFC) neurons projecting to the NAc in KI mice. Interestingly, NL3 re-expression in the mPFC, but not in the NAc, rescued the deficit of flexible behaviors and simultaneously restored NAc-MSN encoding, DA dynamics, and mPFC-NAc output in KI mice. Taken together, this study reveals the frontostriatal circuit dysfunction underlying cognitive inflexibility and establishes a critical role of the mPFC NL3 deficiency in this deficit in KI mice. Therefore, these findings provide new insights into the mechanisms of cognitive and behavioral inflexibility and potential intervention strategies.
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Endothelial dysfunction is associated with the progression of sepsis. This study sought to probe the molecular route of sex-determining region on the Y chromosome-box transcription factor 18 (SOX18) in sepsis-associated endothelial injury. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) to establish the sepsis cell model. Cell viability, lactate dehydrogenase (LDH) release, oxidative stress (reactive oxygen species/malondialdehyde/superoxide dismutase), and inflammation (interleukin-1ß/tumor necrosis factor-α/interleukin-6) were evaluated by cell counting kit-8 assay and relevant assay kits. The expression levels of SOX18, microRNA (miR)-204-5p, and cadherin-2 (CDH2) in cells were determined by real-time quantitative polymerase chain reaction and Western blot assay. The interaction of SOX18, miR-204-5p, and CDH2 was analyzed by chromatin immunoprecipitation and dual-luciferase assay. LPS induced HUVECs injury and downregulation of SOX18. SOX18 overexpression increased cell viability, while decreased LDH activity, oxidative stress, and inflammation. SOX18 bound to the miR-204-5p promoter to promote miR-204-5p expression, and further repressed CDH2 expression. miR-204-5p knockdown and CDH2 overexpression abrogated the protective role of SOX18 in HUVECs injury. Overall, SOX18 alleviated LPS-induced injury of HUVECs by promoting miR-204-5p and repressing CDH2, suggesting it as a potential target for sepsis treatment.
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MicroARNs , Sepsis , Humanos , Células Endoteliales de la Vena Umbilical Humana , Lipopolisacáridos , Inflamación , MicroARNs/genética , Factores de Transcripción SOXF/genéticaRESUMEN
As a crucial gene associated with diseases, the SLC29A3 gene encodes the equilibrative nucleoside transporter 3 (ENT3). ENT3 plays an essential regulatory role in transporting intracellular hydrophilic nucleosides, nucleotides, hydrophilic anticancer and antiviral nucleoside drugs, energy metabolism, subcellular localization, protein stability, and signal transduction. The mutation and inactivation of SLC29A3 are intimately linked to the occurrence, development, and prognosis of various human tumors. Moreover, many hereditary human diseases, such as H syndrome, pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) syndrome, Faisalabad histiocytosis (FHC), are related to SLC29A3 mutations. This review explores the mechanisms of SLC29A3 mutations and expression alterations in inherited disorders and cancers. Additionally, we compile studies on the inhibition of ENT3, which may serve as an effective strategy to potentiate the anticancer activity of chemotherapy. Thus, the synopsis of genetics, permeant function and drug therapy of ENT3 provides a new theoretical and empirical foundation for the diagnosis, prognosis of evaluation and treatment of various related diseases.
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Diabetes Mellitus Tipo 2 , Histiocitosis , Neoplasias , Humanos , Nucleótidos/metabolismo , Mutación , Histiocitosis/genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Nucleósidos/genética , Proteínas de Transporte de Nucleósidos/metabolismoRESUMEN
Microglia maintain homeostasis in the central nervous system through phagocytic clearance of protein aggregates and cellular debris. This function deteriorates during ageing and neurodegenerative disease, concomitant with cognitive decline. However, the mechanisms of impaired microglial homeostatic function and the cognitive effects of restoring this function remain unknown. We combined CRISPR-Cas9 knockout screens with RNA sequencing analysis to discover age-related genetic modifiers of microglial phagocytosis. These screens identified CD22, a canonical B cell receptor, as a negative regulator of phagocytosis that is upregulated on aged microglia. CD22 mediates the anti-phagocytic effect of α2,6-linked sialic acid, and inhibition of CD22 promotes the clearance of myelin debris, amyloid-ß oligomers and α-synuclein fibrils in vivo. Long-term central nervous system delivery of an antibody that blocks CD22 function reprograms microglia towards a homeostatic transcriptional state and improves cognitive function in aged mice. These findings elucidate a mechanism of age-related microglial impairment and a strategy to restore homeostasis in the ageing brain.
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Envejecimiento/fisiología , Encéfalo/citología , Homeostasis/efectos de los fármacos , Microglía/efectos de los fármacos , Ácido N-Acetilneuramínico/farmacología , Fagocitosis/efectos de los fármacos , Lectina 2 Similar a Ig de Unión al Ácido Siálico/antagonistas & inhibidores , Envejecimiento/efectos de los fármacos , Envejecimiento/genética , Animales , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Proteína 9 Asociada a CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Cognición/efectos de los fármacos , Cognición/fisiología , Femenino , Homeostasis/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/citología , Ácido N-Acetilneuramínico/química , Fagocitosis/genética , Análisis de Secuencia de ARN , Lectina 2 Similar a Ig de Unión al Ácido Siálico/genética , Lectina 2 Similar a Ig de Unión al Ácido Siálico/metabolismoRESUMEN
SignificanceNeurodegenerative diseases are poorly understood and difficult to treat. One common hallmark is lysosomal dysfunction leading to the accumulation of aggregates and other undegradable materials, which cause damage to brain resident cells. Lysosomes are acidic organelles responsible for breaking down biomolecules and recycling their constitutive parts. In this work, we find that the antiinflammatory and neuroprotective compound, discovered via a phenotypic screen, imparts its beneficial effects by targeting the lysosome and restoring its function. This is established using a genome-wide CRISPRi target identification screen and then confirmed using a variety of lysosome-targeted studies. The resulting small molecule from this study represents a potential treatment for neurodegenerative diseases as well as a research tool for the study of lysosomes in disease.
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Antiinflamatorios/farmacología , Lisosomas/efectos de los fármacos , Enfermedades Neurodegenerativas/metabolismo , Animales , Antiinflamatorios/química , Biomarcadores , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Desarrollo de Medicamentos , Perfilación de la Expresión Génica , Humanos , Ratones , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/etiología , Enfermedades Neurodegenerativas/patología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Proteínas Smad/agonistasRESUMEN
BACKGROUND: DNA sequencing is a critical tool in modern biology. Over the last two decades, it has been revolutionized by the advent of massively parallel sequencing, leading to significant advances in the genome and transcriptome sequencing of various organisms. Nevertheless, challenges with accuracy, lack of competitive options and prohibitive costs associated with high throughput parallel short-read sequencing persist. RESULTS: Here, we conduct a comparative analysis using matched DNA and RNA short-reads assays between Element Biosciences' AVITI and Illumina's NextSeq 550 chemistries. Similar comparisons were evaluated for synthetic long-read sequencing for RNA and targeted single-cell transcripts between the AVITI and Illumina's NovaSeq 6000. For both DNA and RNA short-read applications, the study found that the AVITI produced significantly higher per sequence quality scores. For PCR-free DNA libraries, we observed an average 89.7% lower experimentally determined error rate when using the AVITI chemistry, compared to the NextSeq 550. For short-read RNA quantification, AVITI platform had an average of 32.5% lower error rate than that for NextSeq 550. With regards to synthetic long-read mRNA and targeted synthetic long read single cell mRNA sequencing, both platforms' respective chemistries performed comparably in quantification of genes and isoforms. The AVITI displayed a marginally lower error rate for long reads, with fewer chemistry-specific errors and a higher mutation detection rate. CONCLUSION: These results point to the potential of the AVITI platform as a competitive candidate in high-throughput short read sequencing analyses when juxtaposed with the Illumina NextSeq 550.
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Secuenciación de Nucleótidos de Alto Rendimiento , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos , Análisis de Secuencia de ARN/métodos , Humanos , Análisis de la Célula Individual/métodos , Biblioteca de GenesRESUMEN
Carbonyl is highly accessible and acts as an essential functional group in chemical synthesis. However, the direct catalytic deoxygenative functionalization of carbonyl compounds via a putative metal carbene intermediate is a formidable challenge due to the requirement of a high activation energy for the cleavage of strong CâO double bonds. Here, we report a class of bench stable and readily available Cp*Mo(II)-complexes as efficient deoxygenation catalysts that could catalyze the direct intermolecular deoxygenative coupling of carbonyl compounds with alkynes. Enabled by this powerful Cp*Mo(II)-catalyst, various valuable heteroarenes (10 different classes) were obtained in generally good yields and remarkable chemo- and regioselectivities. Mechanistic studies suggested that this reaction might proceed via a sequence of CâO double bonds cleavage, carbene-alkyne metathesis, cyclization, and aromatization processes. This strategy not only provided a general catalytic platform for the rapid preparation of heteroarenes but also opened a new window for the applications of Cp*Mo(II)-catalysts in organic synthesis.
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Conventional Li-ion battery intercalation cathodes leverage charge compensation that is formally associated with redox on the transition metal. Employing the anions in the charge compensation mechanism, so-called anion redox, can yield higher capacities beyond the traditional limitations of intercalation chemistry. Here, we aim to understand the structural considerations that enable anion oxidation and focus on processes that result in structural changes, such as the formation of persulfide bonds. Using a Li-rich metal sulfide as a model system, we present both first-principles simulations and experimental data that show that cation vacancies are required for anion oxidation. First-principles simulations show that the oxidation of sulfide to persulfide only occurs when a neighboring vacancy is present. To experimentally probe the role of vacancies in anion redox processes, we introduce vacancies into the Li2TiS3 phase while maintaining a high valency of Ti. When the cation sublattice is fully occupied and no vacancies can be formed through transition metal oxidation, the material is electrochemically inert. Upon introduction of vacancies, the material can support high degrees of anion redox, even in the absence of transition metal oxidation. The model system offers fundamental insights to deepen our understanding of structure-property relationships that govern reversible anion redox in sulfides and demonstrates that cation vacancies are required for anion oxidation, in which persulfides are formed.
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The hallmarks of stem cells, such as proliferation, self-renewal, development, differentiation, and regeneration, are critical to maintain stem cell identity which is sustained by genetic and epigenetic factors. Super-enhancers (SEs), which consist of clusters of active enhancers, play a central role in maintaining stemness hallmarks by specifically transcriptional model. The SE-navigated transcriptional complex, including SEs, non-coding RNAs, master transcriptional factors, Mediators and other co-activators, forms phase-separated condensates, which offers a toggle for directing diverse stem cell fate. With the burgeoning technologies of multiple-omics applied to examine different aspects of SE, we firstly raise the concept of "super-enhancer omics", inextricably linking to Pan-omics. In the review, we discuss the spatiotemporal organization and concepts of SEs, and describe links between SE-navigated transcriptional complex and stem cell features, such as stem cell identity, self-renewal, pluripotency, differentiation and development. We also elucidate the mechanism of stemness and oncogenic SEs modulating cancer stem cells via genomic and epigenetic alterations hijack in cancer stem cell. Additionally, we discuss the potential of targeting components of the SE complex using small molecule compounds, genome editing, and antisense oligonucleotides to treat SE-associated organ dysfunction and diseases, including cancer. This review also provides insights into the future of stem cell research through the paradigm of SEs.
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Elementos de Facilitación Genéticos , Células Madre , Humanos , Animales , Células Madre/metabolismo , Células Madre/citología , Genómica/métodos , Epigénesis Genética , Diferenciación Celular/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patologíaRESUMEN
0D organic-inorganic metal halides (OIMHs) provide unprecedented versatility in structures and photoluminescence properties. Here, a series of bluish-white emissive 0D OIMHs, (TPE-TPP)2Sb2BrxCl8-x (x = 1.16 to 8), are prepared by assembling the 1-triphenylphosphonium-4-(1,2,2-triphenylethenyl)benzene cation (TPE-TPP)+ with antimony halides anions. Based on experimental characterizations and theoretical calculations, the emission of the 0D OIMHs are attributed to the fluorescence of the organic cations with aggregation-induced emission (AIE) properties. The 0D structure minimized the molecular motion and intermolecular interactions between (TPE-TPP)+ cations, effectively suppressing the non-radiative recombination processes. Consequently, the photoluminescence quantum efficiency (PLQE) of (TPE-TPP)2Sb2Br1.16Cl6.84 is significantly enhanced to 55.4% as compared to the organic salt (TPE-TPP)Br (20.5%). The PLQE of (TPE-TPP)2Sb2BrxCl8-x can also be readily manipulated by halide substitution, due to the competitive processes between non-radiative recombination on the inorganic moiety and the energy transfer from inorganic to organic. In addition, electrically driven light-emitting diodes (LEDs) are fabricated based on (TPE-TPP)2Sb2Br1.16Cl6.84 emitter, which exhibited bluish-white emission with a maximum external quantum efficiency (EQE) of 1.1% and luminance of 335 cd m-2. This is the first report of electrically driven LED based on 0D OIMH with bluish-white emission.
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Primary cilia are microtubule-based sensory organelles that project from the apical surface of most mammalian cells, including oligodendrocytes, which are myelinating cells of the central nervous system (CNS) that support critical axonal function. Dysfunction of CNS glia is associated with aging-related white matter diseases and neurodegeneration, and ciliopathies are known to affect CNS white matter. To investigate age-related changes in ciliary profile, we examined ciliary length and frequency in the retinogeniculate pathway, a white matter tract commonly affected by diseases of aging but in which expression of cilia has not been characterized. We found expression of Arl13b, a marker of primary cilia, in a small group of Olig2-positive oligodendrocytes in the optic nerve, optic chiasm, and optic tract in young and aged C57BL/6 wild-type mice. While the ciliary length and ciliated oligodendrocyte cells were constant in young mice in the retinogeniculate pathway, there was a significant increase in ciliary length in the anterior optic nerve as compared to the aged animals. Morphometric analysis confirmed a specific increase in the ciliation rate of CC1+ /Olig2+ oligodendrocytes in aged mice compared with young mice. Thus, the prevalence of primary cilia in oligodendrocytes in the visual pathway and the age-related changes in ciliation suggest that they may play important roles in white matter and age-associated optic neuropathies.