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Single-cell analyses parse the brain's billions of neurons into thousands of 'cell-type' clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use.
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Encéfalo , Epigenômica , Vias Neurais , Neurônios , Animais , Camundongos , Tonsila do Cerebelo , Encéfalo/citologia , Encéfalo/metabolismo , Sequência Consenso , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Hipotálamo/citologia , Mesencéfalo/citologia , Vias Neurais/citologia , Neurônios/metabolismo , Neurotransmissores/metabolismo , Sequências Reguladoras de Ácido Nucleico , Rombencéfalo/citologia , Análise de Célula Única , Tálamo/citologia , Fatores de Transcrição/metabolismoRESUMO
Hydrogen peroxide (H2O2), a key reactive oxygen species (ROS), plays crucial roles in redox signaling pathways and immune responses associated with cell proliferation, differentiation, migration, and disease progression. The selective monitoring of overproduced H2O2 is important for understanding the diagnosis and pathogenesis of diseases such as cardiovascular disease, cancers, diabetes, Parkinson's disease, Alzheimer's disease, and inflammation. In this paper, an AIE fluorescent probe BQM-H2O2 was developed by connecting phenyl borate with the fluorophore BQM-PNH for selective detection of H2O2. In the presence of H2O2 at fw = 99% (pH = 7.4, 1% DMSO), the probe BQM-H2O2 could generate strong fluorescent signals due to the oxidation of the borate ester. The probe exhibited high selectivity and a low detection limit toward H2O2 with the calculated LOD of 112.6 nM. Importantly, it was employed in the detection of exogenous and endogenous hydrogen peroxide in 4T1 cells with low cytotoxicity. This probe has also been successfully applied to imaging of H2O2 in Blab/c mice bearing 4T1 graft tumors.
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Corantes Fluorescentes , Peróxido de Hidrogênio , Imagem Óptica , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Animais , Camundongos , Estrutura Molecular , Humanos , Camundongos Endogâmicos BALB C , Feminino , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Relação Estrutura-AtividadeRESUMO
Dragon fruit stem disease significantly affects both the quality and yield of dragon fruit. Therefore, there is an urgent need for an efficient, high-precision intelligent detection method to address the challenge of disease detection. To address the limitations of traditional methods, including slow detection and weak micro-integration capability, this paper proposes an improved YOLOv8-G algorithm. The algorithm reduces computational redundancy by introducing the C2f-Faster module. The loss function was modified to the structured intersection over union (SIoU), and the coordinate attention (CA) and content-aware reorganization feature extraction (CARAFE) modules were incorporated. These enhancements increased the model's stability and improved its accuracy in recognizing small targets. Experimental results showed that the YOLOv8-G algorithm achieved a mean average precision (mAP) of 83.1% and mAP50:95 of 48.3%, representing improvements of 3.3% and 2.3%, respectively, compared to the original model. The model size and floating point operations per second (FLOPS) were reduced to 4.9 MB and 6.9 G, respectively, indicating reductions of 20% and 14.8%. The improved model achieves higher accuracy in disease detection while maintaining a lighter weight, serving as a valuable reference for researchers in the field of dragon fruit stem disease detection.
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Algoritmos , Cactaceae , Frutas , Caules de Planta , Cactaceae/química , Frutas/química , Doenças das Plantas , Caules de Planta/químicaRESUMO
Sulfatase participates in a variety of physiological processes in organisms including hormone regulation, cell signaling, and bacterial pathogenesis. Current sulfatase fluorescent probes can be used to track sulfate esterase overexpression in cancer cells for diagnostic purposes and to understand the pathological activity of sulfate esterase. However, some sulfatase fluorescent probes based on the hydrolysis of the sulfate bond were easily disturbed by the catalytic activity of sulfatase. Herein, we developed the fluorescent probe BQM-NH2 for sulfatase detection, which was based on the quinoline-malononitrile. The probe BQM-NH2 showed a fast response to sulfatase within 1 min and satisfactory sensitivity with a calculated LOD of 1.73 U/L. Importantly, it was successfully used to monitor endogenous sulfate in tumor cells, indicating BQM-NH2 has the potential to monitor sulfatase under physiological and pathological conditions.
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Corantes Fluorescentes , Sulfatases , Corantes Fluorescentes/química , HidróliseRESUMO
Cysteine (Cys) and homocysteine (Hcy) are involved in maintaining homeostasis in the body and are relevant to various diseases. While the level of Cys and Hcy is much lower than GSH in the living system, which leads to a major challenge to selectively identify Cys/Hcy in the presence of large amounts of GSH. In this paper, an AIE fluorescent probe SQM-NBD was obtained by connecting NBD to the hydroxyl group of the fluorophore SQM-OH for selective detection of Cys/Hcy. Probe SQM-NBD had no fluorescence itself. But, under the disturbance of GSH, the fluorescence signal of probe SQM-NBD could be turned on by Cys/Hcy. The study of the response mechanism showed that probe SQM-NBD could release both SQM-OH and Cys/Hcy-NBD after reacting with Cys/Hcy. While Cys/Hcy continued to quench the fluorescence of SQM-OH through the combination of Michael addition and the ion rich environment, resulting in only the fluorescence signal of Cys/Hcy-NBD being observed. SQM-NBD appeared superior sensitivity to Cys/Hcy, with LOD of 54 nM and 72 nM, respectively. Significantly, probe SQM-NBD realized the application of fluorescence imaging of Cys/Hcy in HeLa cells, indicating that probe SQM-NBD has the potential for Cys/Hcy identification under physiological and pathological conditions.
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Cisteína , Corantes Fluorescentes , Glutationa , Células HeLa , Homocisteína , HumanosRESUMO
With the development of the Internet of things (IoT), federated learning (FL) has received increasing attention as a distributed machine learning (ML) framework that does not require data exchange. However, current FL frameworks follow an idealized setup in which the task size is fixed and the storage space is unlimited, which is impossible in the real world. In fact, new classes of these participating clients always emerge over time, and some samples are overwritten or discarded due to storage limitations. We urgently need a new framework to adapt to the dynamic task sequences and strict storage constraints in the real world. Continuous learning or incremental learning is the ultimate goal of deep learning, and we introduce incremental learning into FL to describe a new federated learning framework. New generation federated learning (NGFL) is probably the most desirable framework for FL, in which, in addition to the basic task of training the server, each client needs to learn its private tasks, which arrive continuously independent of communication with the server. We give a rigorous mathematical representation of this framework, detail several major challenges faced under this framework, and address the main challenges of combining incremental learning with federated learning (aggregation of heterogeneous output layers and the task transformation mutual knowledge problem), and show the lower and upper baselines of the framework.
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Algoritmos , Aprendizado de Máquina , Humanos , ComputadoresRESUMO
OBJECTIVE: To develop and verify a flow cytometric measurement of reticulocytes (RETs) micronucleus in rat bone marrow. METHODS: In our flow cytometric protocol, reticulocytes, leukocytes and DNA were labeled by anti-CD71-fluorescein isothiocyanate (FITC), anti-CD45-phycoerythrin (PE) and DRAQ5, respectively. Sprague-Dawley (SD) rats were assigned to four treatment groups randomly, and were exposed to ethyl methanesulfonate (EMS), cyclophosphamide (CP), ethyl nitrosourea (ENU) and colchicine (COL) respectively. Each treatment group was divided into four subgroups (5 rats per subgroup) according to different exposure dosage. A exposure dose of 0 was used as vehicle control for each group. Rats were administered with testing mutagens by gavage twice with a 24 h interval. Bone marrow from both femurs were collected 24 h after the last administration. The frequency of micronucleated reticulocytes (MN-RETs) and the percentage of reticulocytes (RETs%) were determined by flow cytometric measurement established in this study. And the manual counting method with microscope (by Giemsa staining) was conducted at the same time. RESULTS: A method for detection of reticulocyte micronucleus in bone marrow based on flow cytometry was successfully established. The MN-RETs in rat bone marrow of 20 SD rats treated by vehicle (i.e., background value of MN-RETs) was 0.83±0.12 by this method. The background value of MN-RETs in manual enumeration method was 1.43±0.44. It was obvious that the flow cytometric method had lower background value and more stable results. The trend, in which MN-RETs ascended and RETs% descended with increasing dose, can be detected by both methods in rats that exposed to EMS, CP, ENU and COL. Both methods were good to detect the correlation of induced-MN-RETs with four testing mutagens (the correlation coefficients were ranged from 0.834 3 to 0.913 7). CONCLUSION: With its sensitivity, rapidity, easy operation and low background value, the three-color flow cytometric enumerative protocol established in our laboratory can be used as a good substitute for manual micronucleus counting method and used in genotoxicity assessment of chemical substances.
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Medula Óssea , Citometria de Fluxo , Reticulócitos , Animais , Testes para Micronúcleos , Ratos , Ratos Sprague-Dawley , Reticulócitos/citologiaRESUMO
OBJECTIVE: This study was designed to determine the genotoxicity of 2-methylfuran based on a multi-endpoint genotoxicity test system. METHODS: The SPF-grade male SD rats(n = 30) were randomized to six treatment groups, i. e. 4 treatment groups(25, 50, 100 and 150 mg/kg), a control group(vegetable oil) and a positive groups(N-ethyl-N-nitrosourea, 80 mg/kg). All treatments were administrated by gavage for continuous 3 days. Tail vein blood for comet assay was collected at 3 h after the final administration. Pig-a gene mutation assays were performed on days 0(one day before gavage), 14 and 28. Micronucleus tests in peripheral blood using flow cytometry were performed on days 0 and 4. RESULTS: A statistically significant increase in tail intensity was observed at 150 mg/kg for peripheral blood in comet assay. There was no significant difference among the groups in mutant cell frequency of erythrocytes and reticulocytes at 2 timepoints in Pig-a gene mutation assay, and no significant difference among the groups in the frequency of micronucleus in micronucleus test. CONCLUSION: The result of genotoxicity tests suggested that 2-methylfuran was probably not mutagenic in vivo after acute exposure.
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Eritrócitos , Animais , Ensaio Cometa , Furanos , Masculino , Testes para Micronúcleos , Testes de Mutagenicidade , Ratos , Ratos Sprague-DawleyRESUMO
A new genus and two new species, Tholimantispa zuoae gen. et sp. nov. and Mantispidipterella curvis sp. nov. are described from the Upper Cretaceous of northern Myanmar amber collected in 2015. Tholimantispa zuoae gen. et sp. nov. is characterized by its distinct pterostigma, broad costal space, bifurcate humeral veinlets, and so forth, and Mantispidipterella curvis sp. nov. is different from Mantispidipterella longissima Liu, Lu et Zhang, 2017 in its ScP (subcosta posterior) distinctly curved at fusing point with RA (radius anterior), RP (radius posterior) abruptly and angularly curved at ra-rp (crossvein between RA and RP), AA3 (third branches of the anterior anal vein) present. The new fossil species enrich the diversity of Dipteromantispidae in the Cretaceous.
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In recent years, as more and more fossil species of berothids from Myanmar have been reported, the species and morphological diversity of Berothidae continues to increase. Herein, one new species of Berothidae, Aggregataberotha paucipunctata sp. nov., and one new genus, Sejunctaberotha gen. nov., with three new species (Sejunctaberotha sphaerica gen. et sp. nov., Sejunctaberotha tenuis gen. et sp. nov. and Sejunctaberotha transversa gen. et sp. nov.) are described from mid-Cretaceous Myanmar amber. A. paucipunctata sp. nov. is assigned to Aggregataberotha Wang, Huang & Wang, 2022, based on the characteristics of the similar female terminalia and wing venation, but can be different from A. punctate regarding the pale pterostigma and a few detailed features of wing venation. Additionally, representatives of Sejunctaberotha gen. nov. are remarkably different from the representatives of the other genera within Berothidae in the configuration of wing venation. For example, Sejunctaberotha gen. nov. has simple subcostal veinlets, obviously free Sc and RA at the apex present both in fore- and hindwings, a single ra-rp crossvein connecting the RA with RP3, a single rp-m crossvein locating before the origin of the MP, a simple CuP and no gradate veins. Interestingly, in one of the specimens of Sejunctaberotha gen. nov., a pair of spherical bulges was found at the end of the antennae. The new genus Sejunctaberotha gen. nov. suggests that Berothidae had a higher potential diversification during the Mesozoic Era.
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Introduction: Private enterprises are playing an increasingly important role in production and employment in China. However, due to less regulation and a stronger profit motivation than state-owned enterprises with more standardized management, a considerable portion of these private enterprises fall short of fulfilling their basic responsibilities for government-mandated old-age insurance. Methods: This study establishes a comprehensive research framework aimed at delving into the precise factors contributing to the lax adherence of private enterprises to their basic old-age insurance obligations. This framework takes into account a range of factors, including enterprise profitability, the external environmental context (specifically the level of regional development), and internal organizational dynamics (such as the presence of labor unions and workers' congresses). To validate this framework, empirical data from a substantial sample of 3,123 private enterprises, which were part of the 10th Chinese Private Enterprise Survey (CPES), were utilized. This study employs the stepwise multiple regression analysis and conducts robustness tests to ensure the model's effectiveness. Results: Enterprise profitability, regional development levels, and the existence of labor unions all wield a positive influence on basic old-age insurance coverage that private enterprises extend to their workforce. Moreover, an intriguing aspect emerges: the developmental stage of the region, as well as the presence of labor unions exercise a negative moderating effect on the relationship between enterprise profitability and the coverage rate of basic old-age insurance. In essence, this implies that the basic old-age insurance coverage rate for private enterprises operating in well-developed regions and those with established labor unions is relatively insulated from fluctuations in profitability. Discussion: To increase the participation rate of private enterprises' basic old-age insurance, it is important to improve the overall development environment for private enterprises, enhance internal organizational mechanisms, and strengthen regulatory oversight of enterprises in various regions.
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Cobertura do Seguro , Setor Privado , China , EmpregoRESUMO
The combination of Alismatis Rhizoma (AR) and Rhizoma Smilacis Glabrae (RSG), as Chinese herb medicine, has been used for their uric acid-lowering effect. However, the effects and mechanism of the combination of the two medicines have not been fully reported. Therefore, to explore the effects of AR-RSG combination decoction on the treatment of chronic hyperuricemia (HUA) in rats as well as the underlying mechanisms, in this study, at the first stage, a long-term HUA rats model was established by gavage of oteracil potassium plus adenine; allopurinol was used as the positive control, and the uric acid-lowering effects of AR or RSG decoction alone with low and high dose were evaluated, respectively. Serum uric acid (UA) and xanthine oxidase (XOD) were determined mainly, and pathological analysis of the kidney and liver was carried out after sacrifice of the animals. And then, at the second stage, four dose groups of AR-RSG combination treatment were investigated in HUA rats. In addition to the indicators measured at the first stage, the expression of urate anion exchanger 1 (URAT1) in rat kidney was determined by immunohistochemistry. We discovered that the UA levels of the model group in both stages were significantly and steadily higher than those of control groups. AR and RSG alone or in combination possess ability to decrease serum UA level of HUA rats, with effects more marked in the combination groups. The uric acid-lowering mechanism of AR-RSG combination may be related to its inhibiting activity of XOD, improving kidney damage and downregulating the expression of URAT1 in kidney.