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After ingestion of toxin-contaminated food, the brain initiates a series of defensive responses (e.g., nausea, retching, and vomiting). How the brain detects ingested toxin and coordinates diverse defensive responses remains poorly understood. Here, we developed a mouse-based paradigm to study defensive responses induced by bacterial toxins. Using this paradigm, we identified a set of molecularly defined gut-to-brain and brain circuits that jointly mediate toxin-induced defensive responses. The gut-to-brain circuit consists of a subset of Htr3a+ vagal sensory neurons that transmit toxin-related signals from intestinal enterochromaffin cells to Tac1+ neurons in the dorsal vagal complex (DVC). Tac1+ DVC neurons drive retching-like behavior and conditioned flavor avoidance via divergent projections to the rostral ventral respiratory group and lateral parabrachial nucleus, respectively. Manipulating these circuits also interferes with defensive responses induced by the chemotherapeutic drug doxorubicin. These results suggest that food poisoning and chemotherapy recruit similar circuit modules to initiate defensive responses.
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Eje Cerebro-Intestino , Núcleos Parabraquiales , Nervio Vago , Animales , Ratones , Neuronas/fisiología , Neuronas Aferentes/fisiología , Nervio Vago/fisiologíaRESUMEN
High-capacity storage technologies are needed to meet our ever-growing data demands1,2. However, data centres based on major storage technologies such as semiconductor flash devices and hard disk drives have high energy burdens, high operation costs and short lifespans2,3. Optical data storage (ODS) presents a promising solution for cost-effective long-term archival data storage. Nonetheless, ODS has been limited by its low capacity and the challenge of increasing its areal density4,5. Here, to address these issues, we increase the capacity of ODS to the petabit level by extending the planar recording architecture to three dimensions with hundreds of layers, meanwhile breaking the optical diffraction limit barrier of the recorded spots. We develop an optical recording medium based on a photoresist film doped with aggregation-induced emission dye, which can be optically stimulated by femtosecond laser beams. This film is highly transparent and uniform, and the aggregation-induced emission phenomenon provides the storage mechanism. It can also be inhibited by another deactivating beam, resulting in a recording spot with a super-resolution scale. This technology makes it possible to achieve exabit-level storage by stacking nanoscale disks into arrays, which is essential in big data centres with limited space.
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Archived formalin-fixed paraffin-embedded (FFPE) samples are the global standard format for preservation of the majority of biopsies in both basic research and translational cancer studies, and profiling chromatin accessibility in the archived FFPE tissues is fundamental to understanding gene regulation. Accurate mapping of chromatin accessibility from FFPE specimens is challenging because of the high degree of DNA damage. Here, we first showed that standard ATAC-seq can be applied to purified FFPE nuclei but yields lower library complexity and a smaller proportion of long DNA fragments. We then present FFPE-ATAC, the first highly sensitive method for decoding chromatin accessibility in FFPE tissues that combines Tn5-mediated transposition and T7 in vitro transcription. The FFPE-ATAC generates high-quality chromatin accessibility profiles with 500 nuclei from a single FFPE tissue section, enables the dissection of chromatin profiles from the regions of interest with the aid of hematoxylin and eosin (H&E) staining, and reveals disease-associated chromatin regulation from the human colorectal cancer FFPE tissue archived for >10 yr. In summary, the approach allows decoding of the chromatin states that regulate gene expression in archival FFPE tissues, thereby permitting investigators to better understand epigenetic regulation in cancer and precision medicine.
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Cromatina , Formaldehído , Cromatina/genética , Epigénesis Genética , Perfilación de la Expresión Génica/métodos , Humanos , Adhesión en Parafina/métodos , Fijación del Tejido/métodosRESUMEN
Plant-pathogen protein-protein interactions (PPIs) play crucial roles in the arm race between plants and pathogens. Therefore, the identification of these interspecies PPIs is very important for the mechanistic understanding of pathogen infection and plant immunity. Computational prediction methods can complement experimental efforts, but their predictive performance still needs to be improved. Motivated by the rapid development of natural language processing and its successful applications in the field of protein bioinformatics, here we present an improved XGBoost-based plant-pathogen PPI predictor (i.e., AraPathogen2.0), in which sequence encodings from the pretrained protein language model ESM2 and Arabidopsis PPI network-related node representations from the graph embedding technique struc2vec are used as input. Stringent benchmark experiments showed that AraPathogen2.0 could achieve a better performance than its precedent version, especially for processing the test data set with novel proteins unseen in the training data.
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Arabidopsis , Mapeo de Interacción de Proteínas , Mapeo de Interacción de Proteínas/métodos , Procesamiento de Lenguaje Natural , Plantas , Proteínas/metabolismo , Arabidopsis/metabolismoRESUMEN
Malignant melanoma (MM) is a highly aggressive and deadly form of skin cancer, primarily caused by recurrence and metastasis. Therefore, it is crucial to investigate the regulatory mechanisms underlying melanoma recurrence and metastasis. Our study has identified a potential targeted regulatory relationship between LINC02202, miR-526b-3p and XBP1 in malignant melanoma. Through the regulation of the miR-526b-3p/XBP1 signalling pathway, LINC02202 may play a role in tumour progression and immune infiltration and inhibiting the expression of LINC02202 can increase the efficacy of immunotherapy for melanoma. Our findings shed light on the impact of LINC02202/XBP1 on the phenotype and function of malignant melanoma cells. Furthermore, this study provides a theoretical foundation for the development of novel immunotherapy strategies for malignant melanoma.
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Melanoma , MicroARNs , Neoplasias Cutáneas , Humanos , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , MicroARNs/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Línea Celular Tumoral , Neoplasias Cutáneas/genética , Sistemas de Liberación de Medicamentos , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Proteína 1 de Unión a la X-Box/genética , Proteína 1 de Unión a la X-Box/metabolismoRESUMEN
N-heterocyclic carbene (NHC)-bound ortho-quinodimethane, served as a nucleophile, has occupied an important position for constructing various all-carbon or heterocyclic compounds and attracted increasing attention for the functionalization of benzylic carbon of aromatic aldehydes, whereas the mechanistic studies on the generation and transformations of dienolate intermediate are rare. In the present study, the mechanism of activation/transformation of aldehyde catalyzed by NHC was theoretically studied using the density functional theory (DFT) method. Based on the calculations, the nucleophilic addition process is the stereoselectivity-determining step with RS-configured product being generated preferentially. Furthermore, non-covalent index (NCI) and atoms-in-molecules (AIM) analyses have been performed to disclose the origin of stereoselectivity, by which the larger number and stronger weak interactions are the key for stabilizing the low-energy transition state and thus leading to the stereoselectivity inducing.
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Epilepsy is a prevalent and severe neurological disorder and approximately 30% of patients are resistant to existing medications. It is of utmost importance to develop alternative therapies to treat epilepsy. Schisandrin B (SchB) is a major bioactive constituent of Schisandra chinensis (Turcz.) Baill and has multiple neuroprotective effects, sedative and hypnotic activities. In this study, we investigated the antiseizure effect of SchB in various mouse models of seizure and explored the underlying mechanisms. Pentylenetetrazole (PTZ), strychnine (STR), and pilocarpine-induced mouse seizure models were established. We showed that injection of SchB (10, 30, 60 mg/kg, i.p.) dose-dependently delayed the onset of generalized tonic-clonic seizures (GTCS), reduced the incidence of GTCS and mortality in PTZ and STR models. Meanwhile, injection of SchB (30 mg/kg, i.p.) exhibited therapeutic potential in pilocarpine-induced status epilepticus model, which was considered as a drug-resistant model. In whole-cell recording from CHO/HEK-239 cells stably expressing recombinant human GABAA receptors (GABAARs) and glycine receptors (GlyRs) and cultured hippocampal neurons, co-application of SchB dose-dependently enhanced GABA or glycine-induced current with EC50 values at around 5 µM, and application of SchB (10 µM) alone did not activate the channels in the absence of GABA or glycine. Furthermore, SchB (10 µM) eliminated both PTZ-induced inhibition on GABA-induced current (IGABA) and strychnine (STR)-induced inhibition on glycine-induced current (Iglycine). Moreover, SchB (10 µM) efficiently rescued the impaired GABAARs associated with genetic epilepsies. In addition, the homologous mutants in both GlyRs-α1(S267Q) and GABAARs-α1(S297Q)ß2(N289S)γ2L receptors by site-directed mutagenesis tests abolished SchB-induced potentiation of IGABA and Iglycine. In conclusion, we have identified SchB as a natural positive allosteric modulator of GABAARs and GlyRs, supporting its potential as alternative therapies for epilepsy.
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Epilepsia , Lignanos , Compuestos Policíclicos , Receptores de Glicina , Ratones , Animales , Humanos , Pilocarpina/efectos adversos , Estricnina/farmacología , Estricnina/uso terapéutico , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Receptores de GABA-A , Glicina/farmacología , Hipnóticos y Sedantes , Ácido gamma-Aminobutírico , CiclooctanosRESUMEN
Many solid crystals exhibit a structural phase transition where a subset of its ions or entire molecules become orientationally ordered. As to why such ordering occurs remains mostly unresolved. We consider the extremely weak magnetic elements arising from the reorientations of the molecules experiencing mutual resonance to play the chief role. Two new features are identified in d-camphor: (1) the magnetic susceptibility abruptly changes when crossing the order-disorder phase transition at TII-III = 239.8 K during cooling and at TIII-II = 245.2 K during warming and (2) the complex dielectric constant exhibits two successive discontinuities only 0.2 K apart near the critical temperatures when the sweeping rate is only 0.1 K/min. We discuss how the change in entropy associated with order-disorder transitions in plastic crystals represents temporal changes rather than spatial changes in the system. Our findings may be extended to study why many other crystalline solids exhibit orientational ordering and irreversibility.
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Benzene is a known contributor to human leukaemia through its toxic effects on bone marrow cells, and epigenetic modification is believed to be a potential mechanism underlying benzene pathogenesis. However, the specific roles of N6-methyladenosine (m6A), a newly discovered RNA post-transcriptional modification, in benzene-induced hematotoxicity remain unclear. In this study, we identified self-renewing malignant proliferating cells in the bone marrow of benzene-exposed mice through in vivo bone marrow transplantation experiments and Competitive Repopulation Assay. Subsequent analysis using whole transcriptome sequencing and RNA m6A methylation sequencing revealed a significant upregulation of RNA m6A modification levels in the benzene-exposed group. Moreover, RNA methyltransferase METTL14, known as a pivotal player in m6A modification, was found to be aberrantly overexpressed in Lin-Sca-1+c-Kit+ (LSK) cells of benzene-exposed mice. Further analysis based on the GEO database showed a positive correlation between the expression of METTL14, mTOR, and GFI and benzene exposure dose. In vitro cellular experiments, employing experiments such as western blot, q-PCR, m6A RIP, and CLIP, validated the regulatory role of METTL14 on mTOR and GFI1. Mechanistically, continuous damage inflicted by benzene exposure on bone marrow cells led to the overexpression of METTL14 in LSK cells, which, in turn, increased m6A modification on the target genes' (mTOR and GFI1) RNA. This upregulation of target gene expression activated signalling pathways such as mTOR-AKT, ultimately resulting in malignant proliferation of bone marrow cells. In conclusion, this study offers insights into potential early targets for benzene-induced haematologic malignant diseases and provides novel perspectives for more targeted preventive and therapeutic strategies.
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Adenosina/análogos & derivados , Benceno , Metiltransferasas , Benceno/toxicidad , Animales , Metiltransferasas/genética , Metiltransferasas/metabolismo , Ratones , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/genética , Células Mieloides/efectos de los fármacos , Células Mieloides/patología , Ratones Endogámicos C57BL , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , MasculinoRESUMEN
N6-methyladenosine (m6A) modification is essential for plant growth and development. Exploring m6A methylation patterns in rice tissues is fundamental to understanding the regulatory effects of this modification. Here, we profiled the transcriptome-wide m6A landscapes of rice panicles at the booting stage (PB) and flowering stage (PF), and of flag leaves at the flowering stage (LF). The global m6A level differed significantly among the three tissues and was closely associated with the expression of writer and eraser genes. The methylated gene ratio was higher in the flag leaves than in the panicles. Compared with commonly methylated genes, tissue-specific methylated genes showed lower levels of both m6A modification and expression, and a preference for m6A deposition in the coding sequence region. The m6A profiles of the two organs had more distinct differences than the profiles of the same organ at different stages. A negative correlation between m6A levels and gene expression was observed in PF vs. PB but not in PF vs. LF, indicting the complicated regulatory effect of m6A on gene expression. The distinct expression patterns of m6A reader genes in different tissues indicate that readers may affect gene stability through binding. Overall, our findings demonstrated that m6A modification influences tissue function by regulating gene expression. Our findings provide valuable insights on the regulation and biological functions of m6A modifications in rice.
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Oryza , Transcriptoma , Oryza/genética , ARN Mensajero , Perfilación de la Expresión Génica , Hojas de la Planta/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
OBJECTIVE: Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ptosis, dysarthria, ophthalmoplegia, and distal muscle weakness. Recent studies revealed that GGC repeat expansions in 5'-UTR of LRP12, GIPC1, and NOTCH2NLC are associated with OPDM. Despite these advances, approximately 30% of OPDM patients remain genetically undiagnosed. Herein, we aim to investigate the genetic basis for undiagnosed OPDM patients in two unrelated Chinese Han families. METHODS: Parametric linkage analysis was performed. Long-read sequencing followed by repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to determine the genetic cause. Targeted methylation sequencing was implemented to detect epigenetic changes. The possible pathogenesis mechanism was investigated by quantitative polymerase chain reaction, immunoblotting, RNA fluorescence in situ hybridization, and immunofluorescence staining of muscle biopsy samples. RESULTS: The disease locus was mapped to 12q24.3. Subsequently, GGC repeat expansion in the promoter region of RILPL1 was identified in six OPDM patients from two families, findings consistent with a founder effect, designated as OPDM type 4. Targeted methylation sequencing revealed hypermethylation at the RILPL1 locus in unaffected individuals with ultralong expansion. Analysis of muscle samples showed no significant differences in RILPL1 mRNA or RILPL1 protein levels between patients and controls. Public CAGE-seq data indicated that alternative transcription start sites exist upstream of the RefSeq-annotated RILPL1 transcription start site. Strand-specific RNA-seq data revealed bidirectional transcription from the RILPL1 locus. Finally, fluorescence in situ hybridization/immunofluorescence staining showed that both sense and antisense transcripts formed RNA foci, and were co-localized with hnRNPA2B1 and p62 in the intranuclear inclusions of OPDM type 4 patients. INTERPRETATION: Our findings implicate abnormal GGC repeat expansions in the promoter region of RILPL1 as a novel genetic cause for OPDM, and suggest a methylation mechanism and a potential RNA toxicity mechanism are involved in OPDM type 4 pathogenesis. ANN NEUROL 2022;92:512-526.
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Distrofias Musculares , Adulto , Humanos , Hibridación Fluorescente in Situ , Cuerpos de Inclusión Intranucleares/patología , Distrofias Musculares/genética , Linaje , ARN , Expansión de Repetición de Trinucleótido/genéticaRESUMEN
AGGF1 is an angiogenic factor with G-Patch and FHA domains 1 described by our group. Gain-of-function mutations in AGGF1 cause Klippel-Trenaunay syndrome, whereas somatic loss-of-function mutations cause cancer. Paraspeckles are small membraneless subnuclear structures with a diameter of 0.5-1 µm, and composed of lncRNA NEAT1 as the scaffold and three core RNA-binding proteins NONO, PSPC1, and PSF. Here, we show that AGGF1 is a key regulatory and structural component of paraspeckles that induces paraspeckle formation, forms an outside rim of paraspeckles, wraps around the NONO/PSF/PSPC1/NEAT1 core, and regulates the size and number of paraspeckles. AGGF1-paraspeckles are larger (>1 µm) than conventional paraspeckles. RNA-FISH in combination with immunostaining shows that AGGF1, NONO, and NEAT1_2 co-localize in 20.58% of NEAT1_2-positive paraspeckles. Mechanistically, AGGF1 interacts with NONO, PSF, and HNRNPK, and upregulates NEAT1_2, a longer, 23 kb NEAT1 transcript with a key role in regulation of paraspeckle size and number. RNA-immunoprecipitation shows that AGGF1 interacts with NEAT1, which may be another possible mechanism underlying the formation of AGGF1-paraspeckles. NEAT1_2 knockdown reduces the number and size of AGGF1-paraspeckles. Functionally, AGGF1 regulates alternative RNA splicing as it decreases the exon skipping/inclusion ratio in a CD44 model. AGGF1 is also localized in some nuclear foci without NEAT1 or NONO, suggesting that AGGF1 is an important liquid-liquid phase separation (LLPS) driver for other types of AGGF1-positive nuclear condensates (referred to as AGGF1-bodies). Our results identify a special type of AGGF1-coated paraspeckles and provide important insights into the formation, structure, and function of paraspeckles.
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Paraspeckles , ARN Largo no Codificante , Núcleo Celular/metabolismo , Dominios Proteicos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
With the explosion of data-centric applications, new in-memory computing technologies, based on nonvolatile memory devices, have become competitive due to their merged logic-memory functionalities. Herein, employing first-principles quantum transport simulation, we theoretically investigate for the first time the electronic and contact properties of two types of monolayer (ML)-MoS2 ferroelectric field-effect transistors (FeFETs) integrated with ferroelectric BiAlO3(0001) (BAO(0001)) polar surfaces. Our study finds that the interfacial properties of the investigated partial FeFET devices are highly tunable by switching the electric polarization of the ferroelectric BAO(0001) dielectric. Specifically, the transition from quasi-Ohmic to the Schottky contact, as well as opposite contact polarity of respective n-type and p-type Schottky contact under two polarization states can be obtained, suggesting their superior performance metrics in terms of nonvolatile information storage. In addition, due to the feature of (quasi-)Ohmic contact in some polarization states, the explored FeFET devices, even when operating in the regular field-effect transistor (FET) mode, can be extremely significant in realizing a desirable low threshold voltage and interfacial contact resistance. In conjunction with the formed van der Waals (vdW) interfaces in ML-MoS2/ferroelectric systems with an interlayer, the proposed FeFETs are expected to provide excellent device performance with regard to cycling endurance and memory density.
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In recent years, α-In2Se3 has attracted great attention in miniaturizing nonvolatile random memory devices because of its room temperature ferroelectricity and atomic thickness. In this work, we construct two-dimensional (2D) van der Waals (vdW) heterostructures α-In2Se3/MoS2 with different ferroelectric polarization and design a 2D graphene (Gr)/In2Se3/MoS2/Gr ferroelectric tunnel junction (FTJ) with the symmetric electrodes. Our calculations show that the band alignment of the heterostructures can be changed from type-I to type-II accompanied by the reversal of the ferroelectric polarization of In2Se3. Furthermore, the ferroelectricity persists in Gr/In2Se3/MoS2/Gr vdW FTJs, and the presence of dielectric layer MoS2 in the FTJs enables the effective modulation of the tunneling barrier by altering the ferroelectric polarization of α-In2Se3, which results in two distinct conducting states denoted as "ON" and "OFF" with a large tunneling electroresistance (TER) ratio exceeding 105%. These findings suggest the importance of ferroelectric vdW heterostructures in the design of FTJs and propose a promising route for applying the 2D ferroelectric/semiconductor heterostructures with out-of-plane polarization in high-density ferroelectric memory devices.
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The majority of biopsies in both basic research and translational cancer studies are preserved in the format of archived formalin-fixed paraffin-embedded (FFPE) samples. Profiling histone modifications in archived FFPE tissues is critically important to understand gene regulation in human disease. The required input for current genome-wide histone modification profiling studies from FFPE samples is either 10-20 tissue sections or whole tissue blocks, which prevents better resolved analyses. But it is desirable to consume a minimal amount of FFPE tissue sections in the analysis as clinical tissues of interest are limited. Here, we present FFPE tissue with antibody-guided chromatin tagmentation with sequencing (FACT-seq), the first highly sensitive method to efficiently profile histone modifications in FFPE tissues by combining a novel fusion protein of hyperactive Tn5 transposase and protein A (T7-pA-Tn5) transposition and T7 in vitro transcription. FACT-seq generates high-quality chromatin profiles from different histone modifications with low number of FFPE nuclei. We proved a very small piece of FFPE tissue section containing â¼4000 nuclei is sufficient to decode H3K27ac modifications with FACT-seq. H3K27ac FACT-seq revealed disease-specific super enhancers in the archived FFPE human colorectal and human glioblastoma cancer tissue. In summary, FACT-seq allows decoding the histone modifications in archival FFPE tissues with high sensitivity and help researchers to better understand epigenetic regulation in cancer and human disease.
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Cromatina/metabolismo , Epigénesis Genética , Histonas/análisis , Animales , Línea Celular , Humanos , Ratones , Procesamiento Proteico-Postraduccional , Proteína Estafilocócica A/metabolismo , Transposasas/metabolismoRESUMEN
The genetically modified (GM) maize GG2 contains gr79-epsps and gat genes, conferring glyphosate tolerance. The present study aimed to investigate potential effects of maize GG2 in a 90-day subchronic feeding study on Wistar Han RCC rats. Maize grains from GG2 or non-GM maize were incorporated into diets at concentrations of 25% and 50% and administered to Wistar Han RCC rats (n = 10/sex/group) for 90 days. The basal-diet group of rats (n = 10/sex/group) were fed with common commercialized rodent diet. Compared with rats fed with the corresponding non-GM maize and the basal-diet, no biologically relevant diï¬erences were observed in rats fed with the maize GG2, according to the results of body weight/gain, feed consumption/utilization, clinical signs, mortality, ophthalmology, clinical pathology (hematology, prothrombin time, urinalysis, serum chemistry), organ weights, and gross and microscopic pathology. Under the conditions of this study, these results indicated that maize GG2 is as safe as the non-GM maize in this 90-day feeding study.
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Carcinoma de Células Renales , Alimentos Modificados Genéticamente , Neoplasias Renales , Ratas , Animales , Ratas Wistar , Ratas Sprague-Dawley , Plantas Modificadas Genéticamente/genética , Zea mays/genética , Alimentación Animal/análisis , GlifosatoRESUMEN
The von Neumann architecture with separate memory and processing presents a serious challenge in terms of device integration, power consumption, and real-time information processing. Inspired by the human brain that has highly parallel computing and adaptive learning capabilities, memtransistors are proposed to be developed in order to meet the requirement of artificial intelligence, which can continuously sense the objects, store and process the complex signal, and demonstrate an "all-in-one" low power array. The channel materials of memtransistors include a range of materials, such as two-dimensional (2D) materials, graphene, black phosphorus (BP), carbon nanotubes (CNT), and indium gallium zinc oxide (IGZO). Ferroelectric materials such as P(VDF-TrFE), chalcogenide (PZT), HfxZr1-xO2(HZO), In2Se3, and the electrolyte ion are used as the gate dielectric to mediate artificial synapses. In this review, emergent technology using memtransistors with different materials, diverse device fabrications to improve the integrated storage, and the calculation performance are demonstrated. The different neuromorphic behaviors and the corresponding mechanisms in various materials including organic materials and semiconductor materials are analyzed. Finally, the current challenges and future perspectives for the development of memtransistors in neuromorphic system applications are presented.
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Inteligencia Artificial , Nanotubos de Carbono , Humanos , EncéfaloRESUMEN
A new oleanane-type triterpenoid saponin, 21ß, 22α-di-O-angeloyl-15α, 16α, 28-trihydroxyolean-12-ene 3ß-O-α-L-rhamnopyranosyl-(1â3)-α-D-xylopyranosyl-(1â3)-ß-D-glucopyranoside (1), together with five known compounds (2-5), were isolated from Camellia nitidissima. Their structures were elucidated based on spectroscopic methods, including extensive NMR and MS spectra. Compound 1 showed potential inhibitory activity on α-glucosidase with the IC50 values of 185.9 ± 44.5 µmol/L.
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Camellia , Saponinas , Triterpenos , Saponinas/farmacología , Saponinas/química , alfa-Glucosidasas , Triterpenos/química , Camellia/química , Estructura MolecularRESUMEN
The mouse is a widely used animal model for studying human reproduction. However, the mice are eccentric implantation, and ovarian progesterone and estrogen are essential for implantation, which is different from human beings. Guinea pigs are unique from mice since, like humans, they are the interstitial implantation, and ovarian progesterone alone seems to be sufficient to allow for implantation. In this study, we firstly analyzed the gene expression profiles in the receptive uterus on day 5 of pregnancy compared to the pre-receptive uterus on day 3 of pregnancy in guinea pigs using the RNA-seq method. In total, 304 up-regulated and 475 down-regulated genes were identified. Gene Ontology and pathway enrichment analyses highlighted the importance of the inflammatory response in the receptive uterus. Through gene network analysis, we identified 24 hub genes, most of which were involved in regulating endometrial receptivity. In addition, we performed a cross-species comparison of differentially expressed genes associated with uterine receptivity. A total of 14 genes were shared among guinea pigs, humans, and mice. Furthermore, Fisher's exact test revealed that gene expression patterns of uterine receptivity were more similar between guinea pigs and humans than between mice and humans. Our study may contribute to increasing the knowledge of uterine receptivity in guinea pigs.
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Progesterona , Transcriptoma , Embarazo , Femenino , Cobayas , Ratones , Humanos , Animales , Progesterona/metabolismo , Útero/metabolismo , Implantación del Embrión/genética , Endometrio/metabolismoRESUMEN
It is crucial to monitor hydrogen sulfide (H2S) because H2S plays a vital role in the regulation of many physiology and pathology processes. Many evidences indicate that endogenous H2S is closely associated with many diseases such as inflammation and cancers. Herein, we reported a novel fluorescent probe BTDI to monitor the fluctuation of H2S based on the excited-state intramolecular proton transfer (ESIPT) mechanism both ex vivo and in vivo. The selectivity of BTDI for H2S is significantly higher than that for biothiols and other potential anions. After the probe responded to H2S, the nucleophilic addition reaction of the H2S with probe BTDI resulted the shifting of maximum emission peak from 630 nm to 542 nm and the fluorescent signals change from red to green emission along with a large Stokes shift (240 nm). Moreover, BTDI can be successfully applied to detect extracellular and endogenous H2S in living cells through fluorescent cell-imaging, which provides a promising tool for the specific recognition of H2S in complex biological systems.