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1.
Bioinformatics ; 40(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38579261

RESUMO

MOTIVATION: Substrings of length k, commonly referred to as k-mers, play a vital role in sequence analysis. However, k-mers are limited to exact matches between sequences leading to alternative constructs. We recently introduced a class of new constructs, strobemers, that can match across substitutions and smaller insertions and deletions. Randstrobes, the most sensitive strobemer proposed in Sahlin (Effective sequence similarity detection with strobemers. Genome Res 2021a;31:2080-94. https://doi.org/10.1101/gr.275648.121), has been used in several bioinformatics applications such as read classification, short-read mapping, and read overlap detection. Recently, we showed that the more pseudo-random the behavior of the construction (measured in entropy), the more efficient the seeds for sequence similarity analysis. The level of pseudo-randomness depends on the construction operators, but no study has investigated the efficacy. RESULTS: In this study, we introduce novel construction methods, including a Binary Search Tree-based approach that improves time complexity over previous methods. To our knowledge, we are also the first to address biases in construction and design three metrics for measuring bias. Our evaluation shows that our methods have favorable speed and sampling uniformity compared to existing approaches. Lastly, guided by our results, we change the seed construction in strobealign, a short-read mapper, and find that the results change substantially. We suggest combining the two results to improve strobealign's accuracy for the shortest reads in our evaluated datasets. Our evaluation highlights sampling biases that can occur and provides guidance on which operators to use when implementing randstrobes. AVAILABILITY AND IMPLEMENTATION: All methods and evaluation benchmarks are available in a public Github repository at https://github.com/Moein-Karami/RandStrobes. The scripts for running the strobealign analysis are found at https://github.com/NBISweden/strobealign-evaluation.

2.
J Agric Food Chem ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651754

RESUMO

Pecan nuts are rich in lipids that tend to deteriorate during storage. Tandem mass-tag-based quantitative proteomics and transcriptomics were used to investigate the changes in the protein and gene profiles of stored pecan kernels for the first time. Our previous lipidomic data were jointly analyzed to elucidate the coordinated changes in lipid molecules and related proteins/genes. The mechanism underlying lipid deterioration in pecan kernels during storage was revealed by multiomics analyses. Lipid metabolism-related pathways were activated during pecan storage. Phospholipases, triacylglycerol lipases, lipoxygenases, and oil body-related proteins/genes were highly expressed during storage, revealing their involvement in lipid deterioration. These data provide rich information and will be valuable for future genetic or chemical research to alleviate lipid deterioration in pecans.

3.
Gigascience ; 13(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38373745

RESUMO

BACKGROUND: Cell clustering is a pivotal aspect of spatial transcriptomics (ST) data analysis as it forms the foundation for subsequent data mining. Recent advances in spatial domain identification have leveraged graph neural network (GNN) approaches in conjunction with spatial transcriptomics data. However, such GNN-based methods suffer from representation collapse, wherein all spatial spots are projected onto a singular representation. Consequently, the discriminative capability of individual representation feature is limited, leading to suboptimal clustering performance. RESULTS: To address this issue, we proposed SGAE, a novel framework for spatial domain identification, incorporating the power of the Siamese graph autoencoder. SGAE mitigates the information correlation at both sample and feature levels, thus improving the representation discrimination. We adapted this framework to ST analysis by constructing a graph based on both gene expression and spatial information. SGAE outperformed alternative methods by its effectiveness in capturing spatial patterns and generating high-quality clusters, as evaluated by the Adjusted Rand Index, Normalized Mutual Information, and Fowlkes-Mallows Index. Moreover, the clustering results derived from SGAE can be further utilized in the identification of 3-dimensional (3D) Drosophila embryonic structure with enhanced accuracy. CONCLUSIONS: Benchmarking results from various ST datasets generated by diverse platforms demonstrate compelling evidence for the effectiveness of SGAE against other ST clustering methods. Specifically, SGAE exhibits potential for extension and application on multislice 3D reconstruction and tissue structure investigation. The source code and a collection of spatial clustering results can be accessed at https://github.com/STOmics/SGAE/.


Assuntos
Benchmarking , Perfilação da Expressão Gênica , Animais , Análise por Conglomerados , Mineração de Dados , Drosophila/genética
4.
Brain Connect ; 14(1): 48-59, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38063007

RESUMO

Introduction: In resting-state functional magnetic resonance imaging (rs-fMRI) studies, global signal regression (GSR) is a controversial preprocessing strategy. It effectively eliminates global noise driven by motion and respiration but also can introduce artifacts and remove functionally relevant metabolic information. Most preclinical rs-fMRI studies are performed in anesthetized animals, and anesthesia will alter both metabolic and neuronal activity. Methods: In this study, we explored the effect of GSR on rs-fMRI data collected under anesthetized and awake state in mice (n = 12). We measured global signal amplitude, and also functional connectivity (FC), functional connectivity density (FCD) maps, and brain modularity, all commonly used data-driven analysis methods to quantify connectivity patterns. Results: We found that global signal amplitude was similar between the awake and anesthetized states. However, GSR had a different impact on connectivity networks and brain modularity changes between states. We demonstrated that GSR had a more prominent impact on the anesthetized state, with a greater decrease in functional connectivity and increased brain modularity. We classified mice using the change in amplitude of brain modularity coefficient (ΔQ) before and after GSR processing. The results revealed that, when compared with the largest ΔQ group, the smallest ΔQ group had increased FCD in the cortex region in both the awake and anesthetized states. This suggests differences in individual mice may affect how GSR differentially affects awake versus anesthetized functional connectivity. Discussion: This study suggests that, for rs-fMRI studies which compare different physiological states, researchers should use GSR processing with caution.


Assuntos
Mapeamento Encefálico , Encéfalo , Camundongos , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Vigília , Imageamento por Ressonância Magnética/métodos
5.
J Neuroinflammation ; 20(1): 277, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001534

RESUMO

Luteolin is a flavonoid found in high concentrations in celery and green pepper, and acts as a neuroprotectant. PSMC5 (proteasome 26S subunit, ATPase 5) protein levels were reduced after luteolin stimulation in activated microglia. We aimed to determine whether regulating PSMC5 expression could inhibit neuroinflammation, and investigate the underlying mechanisms.BV2 microglia were transfected with siRNA PSMC5 before the addition of LPS (lipopolysaccharide, 1.0 µg/ml) for 24 h in serum free DMEM. A mouse model of LPS-induced cognitive and motor impairment was established to evaluate the neuroprotective effects of shRNA PSMC5. Intracerebroventricular administration of shRNA PSMC5 was commenced 7 days prior to i.p. injection of LPS (750 µg/kg). Treatments and behavioral experiments were performed once daily for 7 consecutive days. Behavioral tests and pathological/biochemical assays were performed to evaluate LPS-induced hippocampal damage. Molecular dynamics simulation was used to confirm the interaction between PSMC5 and TLR4 (Toll-like receptor 4) in LPS-stimulated BV2 microglia. SiRNA PSMC5 inhibited BV2 microglial activation, and suppressed the release of inflammatory factors (IL-1ß, COX-2, PGE2, TNF-α, and iNOS) upon after LPS stimulation in BV2 microglia. LPS increased IκB-α and p65 phosphorylation, which was attenuated by siRNA PSMC5. Behavioral tests and pathological/biochemical assays showed that shRNA PSMC5 attenuated LPS-induced cognitive and motor impairments, and restored synaptic ultrastructure and protein levels in mice. ShRNA PSMC5 reduced pro-inflammatory cytokine (TNF-α, IL-1ß, PGE2, and NO) levels in the serum and brain, and relevant protein factors (iNOS and COX-2) in the brain. Furthermore, shRNA PSMC5 upregulated the anti-inflammatory mediators interleukin IL-4 and IL-10 in the serum and brain, and promoted a pro-inflammation-to-anti-inflammation phenotype shift in microglial polarization. Mechanistically, shRNA PSMC5 significantly alleviated LPS-induced TLR4 expression. The polarization of LPS-induced microglial pro-inflammation phenotype was abolished by TLR4 inhibitor and in the TLR-4-/- mouse, as in shRNA PSMC5 treatment. PSMC5 interacted with TLR4 via the amino sites Glu284, Met139, Leu127, and Phe283. PSMC5 site mutations attenuated neuroinflammation and reduced pro-inflammatory factors by reducing TLR4-related effects, thereby reducing TLR4-mediated MyD88 (myeloid differentiation factor 88)-dependent activation of NF-κB. PSMC5 could be an important therapeutic target for treatment of neurodegenerative diseases involving neuroinflammation-associated cognitive deficits and motor impairments induced by microglial activation.


Assuntos
Transtornos Motores , Transdução de Sinais , Animais , Camundongos , Cognição , Ciclo-Oxigenase 2/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/efeitos adversos , Luteolina/farmacologia , Microglia/metabolismo , Doenças Neuroinflamatórias , NF-kappa B/metabolismo , RNA Interferente Pequeno/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
7.
Nano Converg ; 10(1): 37, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37561270

RESUMO

With a high specific capacity and low electrochemical potentials, metal anode batteries that use lithium, sodium and zinc metal anodes, have gained great research interest in recent years, as a potential candidate for high-energy-density storage systems. However, the uncontainable dendrite growth during the repeated charging process, deteriorates the battery performance, reduces the battery life and more importantly, raises safety concerns. With their unique properties, two-dimensional (2D) materials, can be used to modify various components in metal batteries, eventually mitigating the dendrite growth, enhancing the cycling stability and rate capability, thus leading to safe and robust metal anodes. In this paper, we review the recent advances of 2D materials and summarize current research progress of using 2D materials in the applications of (i) anode design, (ii) separator engineering, and (iii) electrolyte modifications by guiding metal ion nucleation, increasing ion conductivity, homogenizing the electric field and ion flux, and enhancing the mechanical strength for safe metal anodes. The 2D material modifications provide the ultimate solution for obtaining dendrite-free metal anodes, realizes the high energy storage application, and indicates the importance of 2D materials development. Finally, in-depth understandings of subsequent metal growth are lacking due to research limitations, while more advanced characterizations are welcome for investigating the metal deposition mechanism. The more facile and simplified preparation of 2D materials possess great prospects in high energy density metal anode batteries, and thus fulfils the development of EVs.

8.
Cell Res ; 33(10): 745-761, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37452091

RESUMO

Since the release of the complete human genome, the priority of human genomic study has now been shifting towards closing gaps in ethnic diversity. Here, we present a fully phased and well-annotated diploid human genome from a Han Chinese male individual (CN1), in which the assemblies of both haploids achieve the telomere-to-telomere (T2T) level. Comparison of this diploid genome with the CHM13 haploid T2T genome revealed significant variations in the centromere. Outside the centromere, we discovered 11,413 structural variations, including numerous novel ones. We also detected thousands of CN1 alleles that have accumulated high substitution rates and a few that have been under positive selection in the East Asian population. Further, we found that CN1 outperforms CHM13 as a reference genome in mapping and variant calling for the East Asian population owing to the distinct structural variants of the two references. Comparison of SNP calling for a large cohort of 8869 Chinese genomes using CN1 and CHM13 as reference respectively showed that the reference bias profoundly impacts rare SNP calling, with nearly 2 million rare SNPs miss-called with different reference genomes. Finally, applying the CN1 as a reference, we discovered 5.80 Mb and 4.21 Mb putative introgression sequences from Neanderthal and Denisovan, respectively, including many East Asian specific ones undetected using CHM13 as the reference. Our analyses reveal the advances of using CN1 as a reference for population genomic studies and paleo-genomic studies. This complete genome will serve as an alternative reference for future genomic studies on the East Asian population.


Assuntos
Diploide , População do Leste Asiático , Genoma Humano , Telômero , Humanos , Masculino , Povo Asiático/genética , População do Leste Asiático/etnologia , População do Leste Asiático/genética , Genoma Humano/genética , Genômica , Telômero/genética
9.
J Colloid Interface Sci ; 650(Pt B): 1762-1772, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37506417

RESUMO

Step-scheme (S-scheme) heterojunctions can efficiently promote the separation of photogenerated carriers while maintaining the strong oxidation/reduction ability of photocatalysts; thus, research attention on S-scheme heterojunctions is increasing year by year. In this study, the S-scheme ZnO@ZnIn2S4 (ZnO@ZIS) heterojunction was prepared successfully. Then, electron spin resonance (ESR) characterization was applied to prove the successful construction of the S-scheme heterojunction. Photoluminescence (PL), time-resolved photoluminescence (TRPL), and photoelectrochemical experiments have demonstrated efficient interfacial charge transport in ZnO@ZIS. Finally, the mechanism of CO2 activation and electron transport was investigated by in situ Fourier transform infrared spectroscopy (FT-IR) and discrete Fourier transform (DFT) calculation analysis. The 40-ZnO@ZIS composite showed the best activity under light, and its CO and CH4 yields reached 39.76 and 3.92 µmol∙g-1∙h-1, respectively. This study provides a solution for optimizing the photocatalytic reduction activity of semiconductor photocatalysts by constructing S-scheme heterojunction materials to improve the CO2 reduction capacity.

10.
Chem Commun (Camb) ; 59(61): 9356-9359, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37431776

RESUMO

Photocatalytic mineralization of organic pollutions and simultaneously converting CO2 to CO (tetracycline → CO2 → CO) represents a fascinating way to solve the environmental and energy crisis. This work demonstrates the excellent mineralization and CO2 reduction performance of S-vacancy CdS and reveals the high efficiency of the carbon self-recycling two-in-one photocatalytic system.

11.
PLoS One ; 18(7): e0288999, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37471436

RESUMO

Castanopsis carlesii (Hemsl.) Hay. is a widely distributed and dominant tree species native to subtropical China with significant ecological and economic value. Due to serious human-related disturbance, its wild resources have been increasingly reduced, and whether may result in the loss of genetic diversity. However, no population genetics studies of natural C. carlesii have been reported to date. Microsatellite markers have been a useful tool in population genetics. Therefore, we developed EST-SSR markers based on the transcriptome sequencing of C. carlesii leaves. A total of 149,380,224 clean reads were obtained, and 63,012 nonredundant unigenes with a mean length of 1,034 bp were assembled and annotated based on sequence similarity searches in the Nr, Nt, KO, SwissProt, PFAM, KOG, and GO databases. The results showed that only 5,559 (8.82%) unigenes were annotated in all seven databases, but 46,338 (73.53%) could be annotated in at least one database. A total of 31,459 potential EST-SSRs were identified in 18,690 unigenes, with an average frequency of one SSR approximately 2 kb. Among the 100 EST-SSR primer pairs designed, 49 primer pairs successfully produced the expected product by amplification, with a success rate of 49%, but only 20 primer pairs showed abundant polymorphisms. Polymorphisms were verified using 25 samples from C. carlesii in Qimen, Anhui. A total of 119 alleles were detected, with a mean number of alleles (Na) of 5.95 per locus and a mean polymorphism information content (PIC) of 0.6125. All the 20 newly developed EST-SSR markers were verified in other Castanopsis species (C. sclerophylla, C. lamontii, C. fargesii, C. eyrei and C. jucunda). Sixteen primer pairs showed successful amplification in all five Castanopsis species (80%), and the transferability ratios ranged from 90% to 100%. These developed EST-SSR markers can be applied to population genetic and germplasm evaluations of C. carlesii and related species.


Assuntos
Polimorfismo Genético , Transcriptoma , Humanos , Transcriptoma/genética , Etiquetas de Sequências Expressas , Marcadores Genéticos/genética , Repetições de Microssatélites/genética , Bases de Dados de Proteínas
12.
Food Chem ; 424: 136377, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37267651

RESUMO

Pecan nuts are highly enriched in phenolic compounds, which contribute to the health benefits of pecans. Phenolic compounds represent the main oxidation reaction substrates, thus leading to quality deterioration, namely pellicle browning or a decrease in beneficial effects during pecan storage. Hence, four different storage conditions were performed for 180 d to simulate real production situations. Targeted metabolomics was chosen to identify the specific phenolic compounds involved in quality deterioration under different storage conditions in 0, 90, and 180 d samples. A total of 118 phenolic compounds were detected, nine of which were identified for the first time in pecan. The total phenolic content (TPC) and antioxidant capacities initially demonstrated high scores, after which they tended to decrease during the storage process. The significantly modified phenolic compounds during storage were selected as the metabolite markers of pecan quality deterioration, including catechin, procyanidin (PA) trimer, PA tetramer, trigalloyl hexahydroxydiphenoyl (HHDP) glucose, and tetragalloyl hexoside. Fresh pecan kernels resulted in more pronounced changes in hydrolysable tannins (HTs), whereas dry kernels resulted in the most accentuated changes in condensed tannins (CTs). To the best of our knowledge, this is the first attempt to study individual phenolic changes during storage of pecan in such massive amounts. The results can offer a valuable theoretical basis for future control of pecan quality deterioration through phenolics during storage.


Assuntos
Carya , Nozes , Nozes/química , Carya/química , Fenóis/análise , Antioxidantes/química , Extratos Vegetais/análise
13.
Small ; 19(40): e2303005, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37269202

RESUMO

A Zn anode can offset the low energy density of a flow battery for a balanced approach toward electricity storage. Yet, when targeting inexpensive, long-duration storage, the battery demands a thick Zn deposit in a porous framework, whose heterogeneity triggers frequent dendrite formation and jeopardizes the stability of the battery. Here, Cu foam is transferred into a hierarchical nanoporous electrode to homogenize the deposition. It begins with alloying the foam with Zn to form Cu5 Zn8 , whose depth is controlled to retain the large pores for a hydraulic permeability ≈10-11  m2 . Dealloying follows to create nanoscale pores and abundant fine pits below 10 nm, where Zn can nucleate preferentially due to the Gibbs-Thomson effect, as supported by a density functional theory simulation. Morphological evolution monitored by in situ microscopy confirms uniform Zn deposition. The electrode delivers 200 h of stable cycles in a Zn-I2 flow battery at 60 mAh cm-2 and 60 mA cm-2 , performance that meets practical demands.

14.
J Biol Chem ; 299(6): 104812, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37172724

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is one of the deadliest and most aggressive hematological malignancies, but its pathological mechanism in controlling cell survival is not fully understood. Oculocerebrorenal syndrome of Lowe is a rare X-linked recessive disorder characterized by cataracts, intellectual disability, and proteinuria. This disease has been shown to be caused by mutation of oculocerebrorenal syndrome of Lowe 1 (OCRL1; OCRL), encoding a phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] 5-phosphatase involved in regulating membrane trafficking; however, its function in cancer cells is unclear. Here, we uncovered that OCRL1 is overexpressed in T-ALL cells, and knockdown of OCRL1 results in cell death, indicating the essential role of OCRL in controlling T-ALL cell survival. We show OCRL is primarily localized in the Golgi and can translocate to plasma membrane (PM) upon ligand stimulation. We found OCRL interacts with oxysterol-binding protein-related protein 4L, which facilitates OCRL translocation from the Golgi to the PM upon cluster of differentiation 3 stimulation. Thus, OCRL represses the activity of oxysterol-binding protein-related protein 4L to prevent excessive PI(4,5)P2 hydrolysis by phosphoinositide phospholipase C ß3 and uncontrolled Ca2+ release from the endoplasmic reticulum. We propose OCRL1 deletion leads to accumulation of PI(4,5)P2 in the PM, disrupting the normal Ca2+ oscillation pattern in the cytosol and leading to mitochondrial Ca2+ overloading, ultimately causing T-ALL cell mitochondrial dysfunction and cell death. These results highlight a critical role for OCRL in maintaining moderate PI(4,5)P2 availability in T-ALL cells. Our findings also raise the possibility of targeting OCRL1 to treat T-ALL disease.


Assuntos
Membrana Celular , Fosfatidilinositol 4,5-Difosfato , Monoéster Fosfórico Hidrolases , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Linfócitos T , Humanos , Membrana Celular/metabolismo , Sobrevivência Celular , Hidrólise , Síndrome Oculocerebrorrenal/enzimologia , Síndrome Oculocerebrorrenal/genética , Fosfatidilinositol 4,5-Difosfato/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Linfócitos T/citologia , Linfócitos T/imunologia , Monoéster Fosfórico Hidrolases/biossíntese , Monoéster Fosfórico Hidrolases/deficiência , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Complexo de Golgi/metabolismo , Ligantes , Transporte Proteico , Sinalização do Cálcio , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Citosol/metabolismo
15.
J Genet Genomics ; 50(9): 713-719, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37054878

RESUMO

Data visualization empowers researchers to communicate their results that support scientific reasoning in an intuitive way. Three-dimension (3D) spatially resolved transcriptomic atlases constructed from multi-view and high-dimensional data have rapidly emerged as a powerful tool to unravel spatial gene expression patterns and cell type distribution in biological samples, revolutionizing the understanding of gene regulatory interactions and cell niches. However, limited accessible tools for data visualization impede the potential impact and application of this technology. Here we introduce VT3D, a visualization toolbox that allows users to explore 3D transcriptomic data, enabling gene expression projection to any 2D plane of interest, 2D virtual slice creation and visualization, and interactive 3D data browsing with surface model plots. In addition, it can either work on personal devices in standalone mode or be hosted as a web-based server. We apply VT3D to multiple datasets produced by the most popular techniques, including both sequencing-based approaches (Stereo-seq, spatial transcriptomics, and Slide-seq) and imaging-based approaches (MERFISH and STARMap), and successfully build a 3D atlas database that allows interactive data browsing. We demonstrate that VT3D bridges the gap between researchers and spatially resolved transcriptomics, thus accelerating related studies such as embryogenesis and organogenesis processes. The source code of VT3D is available at https://github.com/BGI-Qingdao/VT3D, and the modeled atlas database is available at http://www.bgiocean.com/vt3d_example.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Transcriptoma/genética , Software , Bases de Dados Factuais
16.
Cell Death Dis ; 14(3): 174, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36859530

RESUMO

Lupus nephritis (LN) is a type of immune-complex nephritis caused by systemic lupus erythematosus and is a major contributor to mortality and morbidity. Honokiol (HNK) has been found to have a therapeutic effect on LN, but its action mechanism remains unclear. In this study, we first demonstrated that HNK attenuates kidney injury in MRL/lpr mice. Results from RNA sequencing combined with ingenuity pathway analysis suggested that HNK plays an anti-LN role through inhibition of the NLRP3 inflammasome and IL33. GEO chip data, single-cell data, and clinical samples from LN patients demonstrated that the pyroptosis and IL-33/ST2 pathways are abnormally activated during the stage of LN. In vivo, similar to the results of the AAV-mediated NLRP3 shRNA MRL/lpr model, HNK downregulated serum and renal IL-33 levels, and suppressed NLRP3 inflammasome and the IL-33/ST2 axis in the kidney. In vitro, co-culturing NLRP3-overexpressing or IL-33 knocked-down rat renal macrophages with NRK-52E cells confirmed that NLRP3 activation in resident macrophages directly upregulates IL-33, which in turn mediates the IL-33/ST2/NF-κB pathway to promote the inflammatory response of renal tubular epithelial cells. Furthermore, a molecular docking model and surface plasmon resonance analysis were utilized to demonstrate a direct interaction between HNK and NLRP3. In conclusion, this study provides a novel anti-LN treatment strategy in which HNK plays a preventive and therapeutic role against LN by suppressing the abnormal crosstalk between renal resident macrophages and renal tubular epithelial cells by inhibiting the activation of the NLRP3/IL-33/ST2 axis.


Assuntos
Nefrite Lúpica , Camundongos , Animais , Ratos , Camundongos Endogâmicos MRL lpr , Interleucina-33 , Proteína 1 Semelhante a Receptor de Interleucina-1 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Inflamassomos , Simulação de Acoplamento Molecular , Rim , Células Epiteliais , Macrófagos , Receptores de Interleucina-1
17.
Cell ; 186(6): 1279-1294.e19, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36868220

RESUMO

Antarctic krill (Euphausia superba) is Earth's most abundant wild animal, and its enormous biomass is vital to the Southern Ocean ecosystem. Here, we report a 48.01-Gb chromosome-level Antarctic krill genome, whose large genome size appears to have resulted from inter-genic transposable element expansions. Our assembly reveals the molecular architecture of the Antarctic krill circadian clock and uncovers expanded gene families associated with molting and energy metabolism, providing insights into adaptations to the cold and highly seasonal Antarctic environment. Population-level genome re-sequencing from four geographical sites around the Antarctic continent reveals no clear population structure but highlights natural selection associated with environmental variables. An apparent drastic reduction in krill population size 10 mya and a subsequent rebound 100 thousand years ago coincides with climate change events. Our findings uncover the genomic basis of Antarctic krill adaptations to the Southern Ocean and provide valuable resources for future Antarctic research.


Assuntos
Euphausiacea , Genoma , Animais , Relógios Circadianos/genética , Ecossistema , Euphausiacea/genética , Euphausiacea/fisiologia , Genômica , Análise de Sequência de DNA , Elementos de DNA Transponíveis , Evolução Biológica , Adaptação Fisiológica
18.
Mol Microbiol ; 119(1): 126-142, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36537557

RESUMO

In dimorphic fungi, the yeast-to-filament transition critical for cell survival under nutrient starvation is controlled by both activators and repressors. However, very few filamentation repressors are known. Here we report that, in the dimorphic yeast Yarrowia lipolytica, the conserved transcription factor YlNrg1 plays a minor role whereas Fts1, a newly identified Zn(II)2 Cys6 zinc cluster transcription factor, plays a key role in filamentation repression. FTS1 deletion caused hyperfilamentation whereas Fts1 overexpression drastically reduced filamentation. The expression of FTS1 is downregulated substantially during the yeast-to-filament transition. Transcriptome sequencing revealed that Fts1 represses 401 genes, including the filamentation-activating transcription factor genes MHY1, YlAZF1, and YlWOR4 and key cell wall protein genes. Tup1-Ssn6, a general transcriptional corepressor, is involved in the repression of many cellular functions in fungi. We show that both YlTup1 and YlSsn6 strongly repress filamentation in Y. lipolytica. YlTup1 and YlSsn6 together repress 1383 genes, including a large number of transcription factor and cell wall protein genes, which overlap substantially with Fts1-repressed genes. Fts1 interacts with both YlTup1 and YlSsn6, and LexA-Fts1 fusion represses a lexAop-promoter-lacZ reporter in a Tup1-Ssn6-dependent manner. Our findings suggest that Fts1 functions as a transcriptional repressor, directing the repression of target genes through the Tup1-Ssn6 corepressor.


Assuntos
Yarrowia , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/genética , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Yarrowia/genética , Yarrowia/metabolismo
19.
Front Cell Infect Microbiol ; 12: 1040749, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36579341

RESUMO

Background: The effect of chronic psychological stress on hepatitis and liver fibrosis is concerned. However, its mechanism remains unclear. We investigated the effect and mechanism of chronic psychological stress in promoting liver injury and fibrosis through gut. Methods: Sixty male SD rats were randomly assigned to 6 groups. Rat models of chronic psychological stress (4 weeks) and liver fibrosis (8 weeks) were established. The diversity of gut microbiota in intestinal feces, permeability of intestinal mucosa, pathologies of intestinal and liver tissues, collagen fibers, protein expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa ß (NF-κß), tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) in liver tissue, liver function and coagulation function in blood and lipopolysaccharide (LPS) in portal vein blood were detected and analyzed. Results: The diversities and abundances of gut microbiota were significant differences in rats among each group. The pathological lesions of intestinal and liver tissues, decreased expression of occludin protein in intestinal mucosa, deposition of collagen fibers and increased protein expression of TLR4, MyD88, NF-κß, TNF-α and IL-1 in liver tissue, increased LPS level in portal vein blood, and abnormalities of liver function and coagulation function, were observed in rats exposed to chronic psychological stress or liver fibrosis. There were significant differences with normal rats. When the dual intervention factors of chronic psychological stress and liver fibrosis were superimposed, the above indicators were further aggravated. Conclusion: Chronic psychological stress promotes liver injury and fibrosis, depending on changes in the diversity of gut microbiota and increased intestinal permeability caused by psychological stress, LPS that enters liver and acts on TLR4, and active LPS-TLR4 pathway depend on MyD88. It demonstrates the possibility of existence of brain-gut-liver axis.


Assuntos
Lipopolissacarídeos , Receptor 4 Toll-Like , Ratos , Masculino , Animais , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Transdução de Sinais , Fator 88 de Diferenciação Mieloide/metabolismo , Ratos Sprague-Dawley , NF-kappa B/metabolismo , Cirrose Hepática , Interleucina-1/metabolismo , Interleucina-1/farmacologia , Colágeno/metabolismo , Encéfalo/metabolismo
20.
Nano Lett ; 22(24): 10167-10175, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36475688

RESUMO

Vanadium diselenide (VSe2) exhibits versatile electronic and magnetic properties in the trigonal prismatic (H-) and octahedral (T-) phases. Compared to the metallic T-phase, the H-phase with a tunable semiconductor property is predicted to be a ferrovalley material with spontaneous valley polarization. Herein we report an epitaxial growth of the monolayer 2D VSe2 on a mica substrate via the chemical vapor deposition (CVD) method by introducing salt in the precursor. Our first-principles calculations suggest that the monolayer H-phase VSe2 with a large lateral size is thermodynamically favorable. The honeycomb-like structure and the broken symmetry are directly observed by spherical aberration-corrected scanning transmission electron microscopy (STEM) and confirmed by giant second harmonic generation (SHG) intensity. The p-type transport behavior is further evidenced by the temperature-dependent resistance and field-effect device study. The present work introduces a new phase-stable 2D transition metal dichalcogenide, opening the prospect of novel electronic and spintronics device design.

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