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1.
J Agric Food Chem ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38994810

RESUMO

Boletus aereus Fr. ex Bull. stands out as a delectable edible mushroom with high nutritional and medicinal values, featuring polysaccharides as its primary nutrient composition. In our continuous exploration of its beneficial substances, a novel polysaccharide (BAPN-1) with a molecular weight of 2279 kDa was prepared. It was identified as a glucan with a backbone composed of the residues →4)-α-Glcp-(1→ and →4,6)-α-Glcp-(1→ connected in a proportion of 5:1 and a ß-Glcp-(1→ side residue attached at C6 of the →4,6)-α-Glcp-(1→ residue. Biologically, BAPN-1 exhibited broad-spectrum antiproliferative activities against various NHL cells, including HuT-78, OCI-LY1, OCI-LY18, Jurkat, RL, and Karpas-299, with IC50 values of 0.73, 1.21, 3.18, 1.52, 3.34, and 4.25 mg/mL, respectively. Additionally, BAPN-1 significantly induced cell cycle arrest in the G2/M phase and caused apoptosis of NHL cells. Mechanistically, bulk RNA sequencing and Western blot analysis revealed that BAPN-1 could upregulate cyclin B1 and enhance cleaved caspase-9 expression through the inhibition of FGFR3 and RAF-MEK-ERK signaling pathways. This work supports the improved utilization of B. aereus in high-value health products.

2.
Front Vet Sci ; 11: 1388532, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988981

RESUMO

The Arctic fox (Vulpes lagopus) is a species indigenous to the Arctic and has developed unique lipid metabolism, but the mechanisms remain unclear. Here, the significantly increased body weight of Arctic foxes was consistent with the significantly increased serum very-low-density lipoprotein (VLDL), and the 40% crude fat diet further increased the Arctic fox body weight. The enhanced body weight gain stems primarily from increased subcutaneous adipose tissue accumulation. The adipose triacylglycerol and phosphatidylethanolamine were significantly greater in Arctic foxes. The adipose fatty-acid synthase content was significantly lower in Arctic foxes, highlighting the main role of exogenous fatty-acids in fat accumulation. Considering the same diet, liver-derived fat dominates adipose expansion in Arctic foxes. Liver transcriptome analysis revealed greater fat and VLDL synthesis in Arctic foxes, consistent with the greater VLDL. Glucose homeostasis wasn't impacted in Arctic foxes. And the free fatty-acids in adipose, which promote insulin resistance, also did not differ between groups. However, the hepatic glycogen was greater in Arctic foxes and transcriptome analysis revealed upregulated glycogen synthesis, improving glucose homeostasis. These results suggest that the superior fat accumulation capacity and distinct characteristics of hepatic and adipose lipid and glucose metabolism facilitate glucose homeostasis and massive fat accumulation in Arctic foxes.

3.
bioRxiv ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38895239

RESUMO

Post-Acute Sequelae of COVID-19 (PASC) encompasses persistent neurological symptoms, including olfactory and autonomic dysfunction. Here, we report chronic neurological dysfunction in mice infected with a virulent mouse-adapted SARS-CoV-2 that does not infect the brain. Long after recovery from nasal infection, we observed loss of tyrosine hydroxylase (TH) expression in olfactory bulb glomeruli and neurotransmitter levels in the substantia nigra (SN) persisted. Vulnerability of dopaminergic neurons in these brain areas was accompanied by increased levels of proinflammatory cytokines and neurobehavioral changes. RNAseq analysis unveiled persistent microglia activation, as found in human neurodegenerative diseases. Early treatment with antivirals (nirmatrelvir and molnupiravir) reduced virus titers and lung inflammation but failed to prevent neurological abnormalities, as observed in patients. Together these results show that chronic deficiencies in neuronal function in SARS-CoV-2-infected mice are not directly linked to ongoing olfactory epithelium dysfunction. Rather, they bear similarity with neurodegenerative disease, the vulnerability of which is exacerbated by chronic inflammation.

4.
Sci China Life Sci ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38902451

RESUMO

Jerboas is a lineage of small rodents displaying atypical mouse-like morphology with elongated strong hindlimbs and short forelimbs. They have evolved obligate bipedal saltation and acute senses, and been well-adapted to vast desert-like habitats. Using a newly sequenced chromosome-scale genome of the Mongolian five-toed jerboa (Orientallactaga sibirica), our comparative genomic analyses and in vitro functional assays showed that the genetic innovations in both protein-coding and non-coding regions played an important role in jerboa morphological and physiological adaptation. Jerboa-specific amino acid substitutions, and segment insertions/deletions (indels) in conserved non-coding elements (CNEs) were found in components of proteoglycan biosynthesis pathway (XYLT1 and CHSY1), which plays an important role in limb development. Meanwhile, we found specific evolutionary changes functionally associated with energy or water metabolism (e.g., specific amino acid substitutions in ND5 and indels in CNEs physically near ROR2) and senses (e.g., expansion of vomeronasal receptors and the FAM136A gene family) in jerboas. Further dual-luciferase reporter assay verified that some of the CNEs with jerboa-specific segment indels exerted a significantly different influence on luciferase activity, suggesting changes in their regulatory function in jerboas. Our results revealed the potential molecular mechanisms underlying jerboa adaptation since the divergence from the Eocene-Oligocene transition, and provided more resources and new insights to enhance our understanding of the molecular basis underlying the phenotypic diversity and the environmental adaptation of mammals.

5.
ACS Nano ; 18(24): 15915-15924, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38833535

RESUMO

Considering the increasing demand for high-resolution light-emitting diodes (LEDs), it is important that direct fine patterning technologies for LEDs be developed, especially for quantum-dot LEDs (QLEDs). Traditionally, the patterning of QLEDs relies on resin-based photolithography techniques, requiring multiple steps and causing performance deterioration. Nondestructive direct patterning may provide an easy and stepwise method to achieve fine-pixelated units in QLEDs. In this study, two isomeric tridentate cross-linkers (X8/X9) are presented and can be blended into the hole transport layer (HTL) and the emissive layer (EML) of QLEDs. Because of their photosensitivity, the in situ cross-linking process can be efficiently triggered by ultraviolet irradiation, affording high solvent resistance and nondestructive direct patterning of the layers. Red QLEDs using the cross-linked HTL demonstrate an impressive external quantum efficiency of up to 22.45%. Through lithographic patterning enabled by X9, line patterns of HTL and EML films exhibit widths as narrow as 2 and 4 µm, respectively. Leveraging the patterned HTL and EML, we show the successful fabrication of pixelated QLED devices with an area size of 3 × 3 mm2, alongside the successful production of dual-color pixelated QLED devices. These findings showcase the promising potential of direct patterning facilitated by engineered cross-linkers for the cost-effective fabrication of pixelated QLED displays.

6.
Comput Struct Biotechnol J ; 23: 1608-1618, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38680874

RESUMO

Antlers are hallmark organ of deer, exhibiting a relatively high growth rate among mammals, and requiring large amounts of nutrients to meet its development. The rumen microbiota plays key roles in nutrient metabolism. However, changes in the microbiota and metabolome in the rumen during antler growth are largely unknown. We investigated rumen microbiota (liquid, solid, ventral epithelium, and dorsal epithelium) and metabolic profiles of sika deer at the early (EG), metaphase (MG) and fast growth (FG) stages. Our data showed greater concentrations of acetate and propionate in the rumens of sika deer from the MG and FG groups than in those of the EG group. However, microbial diversity decreased during antler growth, and was negatively correlated with short-chain fatty acid (SCFA) levels. Prevotella, Ruminococcus, Schaedlerella and Stenotrophomonas were the dominant bacteria in the liquid, solid, ventral epithelium, and dorsal epithelium fractions. The proportions of Stomatobaculum, Succiniclasticum, Comamonas and Anaerotruncus increased significantly in the liquid or dorsal epithelium fractions. Untargeted metabolomics analysis revealed that the metabolites also changed significantly, revealing 237 significantly different metabolites, among which the concentrations of γ-aminobutyrate and creatine increased during antler growth. Arginine and proline metabolism and alanine, aspartate and glutamate metabolism were enhanced. The co-occurrence network results showed that the associations between the rumen microbiota and metabolites different among the three groups. Our results revealed that the different rumen ecological niches were characterized by distinct microbiota compositions, and the production of SCFAs and the metabolism of specific amino acids were significantly changed during antler growth.

7.
Sci Data ; 11(1): 311, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521795

RESUMO

The pig-nosed turtle (Carettochelys insculpta) represents the only extant species within the Carettochelyidae family, is a unique Trionychia member fully adapted to aquatic life and currently facing endangerment. To enhance our understanding of this species and contribute to its conservation efforts, we employed high-fidelity (HiFi) and Hi-C sequencing technology to generate its genome assembly at the chromosome level. The assembly result spans 2.18 Gb, with a contig N50 of 126 Mb, encompassing 34 chromosomes that account for 99.6% of the genome. The assembly has a BUSCO score above 95% with different databases and strong collinearity with Yangtze giant softshell turtles (Rafetus swinhoei), indicating its completeness and continuity. A total of 19,175 genes and 46.86% repetitive sequences were annotated. The availability of this chromosome-scale genome represents a valuable resource for the pig-nosed turtle, providing insights into its aquatic adaptation and serving as a foundation for future turtle research.


Assuntos
Genoma , Tartarugas , Animais , Cromossomos/genética , Anotação de Sequência Molecular , Filogenia , Sequências Repetitivas de Ácido Nucleico , Tartarugas/genética
8.
Inorg Chem ; 63(7): 3572-3577, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38324777

RESUMO

Cuprous complex scintillators show promise for X-ray detection with abundant raw materials, diverse luminescent mechanisms, and adjustable structures. However, their synthesis typically requires a significant amount of organic solvents, which conflict with green chemistry principles. Herein, we present the synthesis of two high-performance cuprous complex scintillators using a simple mechanochemical method for the first time, namely [CuI(PPh3)2R] (R = 4-phenylpyridine hydroiodide (PH, Cu-1) and 4-(4-bromophenyl)pyridine hydroiodide (PH-Br, Cu-2). Both materials demonstrated remarkable scintillation performances, exhibiting radioluminescence (RL) intensities 1.52 times (Cu-1) and 2.52 times (Cu-2) greater than those of Bi4Ge3O12 (BGO), respectively. Compared to Cu-1, the enhanced RL performance of Cu-2 can be ascribed to its elevated quantum yield of 51.54%, significantly surpassing that of Cu-1 at 37.75%. This excellent luminescent performance is derived from the introduction of PH-Br, providing a more diverse array of intermolecular interactions that effectively constrain molecular vibration and rotation, further suppressing the nonradiative transition process. Furthermore, Cu-2 powder can be prepared into scintillator film with excellent X-ray imaging capabilities. This work establishes a pathway for the rapid, eco-friendly, and cost-effective synthesis of high-performance cuprous complex scintillators.

9.
bioRxiv ; 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38260331

RESUMO

Brain development is highly dynamic and asynchronous, marked by the sequential maturation of functional circuits across the brain. The timing and mechanisms driving circuit maturation remain elusive due to an inability to identify and map maturing neuronal populations. Here we create DevATLAS (Developmental Activation Timing-based Longitudinal Acquisition System) to overcome this obstacle. We develop whole-brain mapping methods to construct the first longitudinal, spatiotemporal map of circuit maturation in early postnatal mouse brains. Moreover, we uncover dramatic impairments within the deep cortical layers in a neurodevelopmental disorders (NDDs) model, demonstrating the utility of this resource to pinpoint when and where circuit maturation is disrupted. Using DevATLAS, we reveal that early experiences accelerate the development of hippocampus-dependent learning by increasing the synaptically mature granule cell population in the dentate gyrus. Finally, DevATLAS enables the discovery of molecular mechanisms driving activity-dependent circuit maturation.

10.
BMC Psychiatry ; 23(1): 930, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-38082408

RESUMO

BACKGROUND AND OBJECTIVE: Loneliness is detrimental to mental health, with university students at higher risk of feeling lonely than other population groups. The mental health of college students is a hot topic at present. Despite numerous studies exploring interventions for loneliness among university students. However, little research has explored early psychological manifestations of university students with different levels of loneliness. Despite numerous studies exploring interventions for loneliness among university students, little research has explored early psychological manifestations of university students with different levels of loneliness. Initial sandplay is a good tool to reveal psychological activity. Therefore, our study aims to explore the characteristics of initial sandplay application among university students with different levels of loneliness. METHODS: We recruited 60 volunteers from a university to perform a sandplay experiment from January to April 2021. The UCLA Loneliness Scale measured the levels of loneliness. These 60 participants were divided into the experimental group (n = 30) and control group (n = 30) according to their levels of loneliness. The experimental group included participants with a scale score of more than 44. Other participants with a scale score of less than 44 belong to the control group. We recorded their sandplay artwork and statistically analyzed it by the Sandplay Process Record Form. Group comparisons were performed using the t-test or Wilcoxon rank-sum test for continuous variables, and the chi-square test or Fisher's exact test for categorical variables. The logistic regression analysis by forward stepwise method was conducted to analyze the sandplay theme features for loneliness. RESULTS: Regarding the sandplay tools, the experimental group used fewer transportation tools (t=-3.608, p < 0.01) and more natural elements (t = 2.176, p < 0.05) than the control group. Moreover, the experimental group created more natural scenes (χ2 = 4.310, p < 0.05) and used less of the lower left (χ2 = 4.593, p < 0.05) and lower right (χ2 = 5.934, p < 0.05) spaces. With regards to sand changes, the experimental group was less likely than the control group to make substantial changes (χ2 = 5.711, p < 0.05) and more likely to make almost no changes (χ2 = 4.022, p < 0.05). In terms of the themes, the experimental group was more likely to exhibit sandplay artwork themes of emptiness (χ2 = 8.864, p < 0.05) and neglect (χ2 = 6.667, p < 0.05), and less likely to show themes of energy (χ2 = 5.079, p < 0.05). In the logistic regression analysis of the sandplay themes, emptiness (OR = 5.714, 95%CI: 1.724-18.944, p = 0.003) and neglect (OR = 7.000, 95%CI: 1.381-35.479, p = 0.010) were demonstrated a nominal association with high levels of loneliness among both groups (F = 16.091, p < 0.01, ΔR2 = 0.193), but failed to pass the Bonferroni testing correction (p threshold < 0.0025). CONCLUSION: University students with higher degree of loneliness do not like to drastic changes and prefer to use natural elements in element selection, while the control group likes to drastic changes and prefers to use transportation tools in element selection. Regression analysis of sandplay theme features revealed emptines and neglect may as significant associated factors for loneliness. We propose sandplay characteristics can help identify university students with different levels of loneliness during psychological evaluations. Therefore, it is important that the school and healthcare systems assist college students in identifying the loneliness through initial sandplay and carrying on the necessary psychological counseling to the lonely student population.


Assuntos
Solidão , Ludoterapia , Humanos , Solidão/psicologia , Universidades , Emoções , Estudantes/psicologia
11.
Elife ; 122023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38134226

RESUMO

As the deepest vertebrate in the ocean, the hadal snailfish (Pseudoliparis swirei), which lives at a depth of 6,000-8,000 m, is a representative case for studying adaptation to extreme environments. Despite some preliminary studies on this species in recent years, including their loss of pigmentation, visual and skeletal calcification genes, and the role of trimethylamine N-oxide in adaptation to high-hydrostatic pressure, it is still unknown how they evolved and why they are among the few vertebrate species that have successfully adapted to the deep-sea environment. Using genomic data from different trenches, we found that the hadal snailfish may have entered and fully adapted to such extreme environments only in the last few million years. Meanwhile, phylogenetic relationships show that they spread into different trenches in the Pacific Ocean within a million years. Comparative genomic analysis has also revealed that the genes associated with perception, circadian rhythms, and metabolism have been extensively modified in the hadal snailfish to adapt to its unique environment. More importantly, the tandem duplication of a gene encoding ferritin significantly increased their tolerance to reactive oxygen species, which may be one of the important factors in their adaptation to high-hydrostatic pressure.


Assuntos
Ecossistema , Vertebrados , Animais , Filogenia , Vertebrados/genética , Cromossomos
12.
Opt Express ; 31(16): 25557-25570, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710439

RESUMO

The extended L-band 4-core Er/Yb co-doped fiber and amplifier (MC-EYDFA) is first proposed and demonstrated, to the best of our knowledge, for space division multiplexing combined with wavelength division multiplexing application. The fiber core co-doped with Er/Yb/P is adopted for bandwidth expansion, and the long wavelength extends to 1625 nm. Numerical simulations further show that efficient amplification and higher saturation power are achieved with the 1018 nm cladding pumping. Based on the integrated 4-core fiber amplifier, an average gain of ∼22 dB covering 1575-1625 nm is experimentally obtained with a 4 W pump power and a 3 dBm total signal power, and the max core-dependent gain (CDG) variation is measured to be 1.7 dB.

13.
Nat Commun ; 14(1): 5617, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37726270

RESUMO

Yak has been subject to natural selection, human domestication and interspecific introgression during its evolution. However, genetic variants favored by each of these processes have not been distinguished previously. We constructed a graph-genome for 47 genomes of 7 cross-fertile bovine species. This allowed detection of 57,432 high-resolution structural variants (SVs) within and across the species, which were genotyped in 386 individuals. We distinguished the evolutionary origins of diverse SVs in domestic yaks by phylogenetic analyses. We further identified 334 genes overlapping with SVs in domestic yaks that bore potential signals of selection from wild yaks, plus an additional 686 genes introgressed from cattle. Nearly 90% of the domestic yaks were introgressed by cattle. Introgression of an SV spanning the KIT gene triggered the breeding of white domestic yaks. We validated a significant association of the selected stratified SVs with gene expression, which contributes to phenotypic variations. Our results highlight that SVs of different origins contribute to the phenotypic diversity of domestic yaks.


Assuntos
Variação Estrutural do Genoma , Oncogenes , Humanos , Bovinos/genética , Animais , Filogenia , Cruzamento , Domesticação
14.
Adv Sci (Weinh) ; 10(28): e2303217, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37526339

RESUMO

Atomic-level structural editing is a promising way for facile synthesis and accurately constructing dielectric/magnetic synergistic attenuated hetero-units in electromagnetic wave absorbers (EWAs), but it is hard to realize. Herein, utilizing the rapid explosive volume expansion of the CoFe-bimetallic energetic metallic triazole framework (CoFe@E-MTF) during the heat treatment, the effective absorption bandwidth and the maximum absorption intensity of a series of atomic CoFe-inserted hierarchical porous carbon (CoFe@HPC) EWAs can be modified under the diverse synthetic temperature. Under the filler loading of 15 wt%, the fully covered X and Ku bands at 3 and 2.5 mm for CoFe@HPC800 and the superb minimum reflection loss (RLmin ) of -53.15 dB and specific reflection loss (SRL) of -101.24 dB mg-1 mm-1 for CoFe@HPC1000 are achieved. More importantly, the single-atomic chemical bonding among Co─Fe on the nanopores is captured by extended X-ray absorption fine structure, which reveals the formation mechanism of nanopore-confined vortical dipoles and magnetic domains. This work heralds the infinite possibilities of atomic editing EWA in the future.

15.
Sci China Life Sci ; 66(11): 2629-2645, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37273070

RESUMO

Although most fishes are ectothermic, some, including tuna and billfish, achieve endothermy through specialized heat producing tissues that are modified muscles. How these heat producing tissues evolved, and whether they share convergent molecular mechanisms, remain unresolved. Here, we generated a high-quality genome from the mackerel tuna (Euthynnus affinis) and investigated the heat producing tissues of this fish by single-nucleus and bulk RNA sequencing. Compared with other teleosts, tuna-specific genetic variation is strongly associated with muscle differentiation. Single-nucleus RNA-seq revealed a high proportion of specific slow skeletal muscle cell subtypes in the heat producing tissues of tuna. Marker genes of this cell subtype are associated with the relative sliding of actin and myosin, suggesting that tuna endothermy is mainly based on shivering thermogenesis. In contrast, cross-species transcriptome analysis indicated that endothermy in billfish relies mainly on non-shivering thermogenesis. Nevertheless, the heat producing tissues of the different species do share some tissue-specific genes, including vascular-related and mitochondrial genes. Overall, although tunas and billfishes differ in their thermogenic strategies, they share similar expression patterns in some respects, highlighting the complexity of convergent evolution.


Assuntos
Temperatura Alta , Atum , Animais , Atum/genética , Termogênese/genética , Peixes/fisiologia , Músculos
16.
Science ; 380(6648): eabl8621, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37262163

RESUMO

The biological mechanisms that underpin primate social evolution remain poorly understood. Asian colobines display a range of social organizations, which makes them good models for investigating social evolution. By integrating ecological, geological, fossil, behavioral, and genomic analyses, we found that colobine primates that inhabit colder environments tend to live in larger, more complex groups. Specifically, glacial periods during the past 6 million years promoted the selection of genes involved in cold-related energy metabolism and neurohormonal regulation. More-efficient dopamine and oxytocin pathways developed in odd-nosed monkeys, which may have favored the prolongation of maternal care and lactation, increasing infant survival in cold environments. These adaptive changes appear to have strengthened interindividual affiliation, increased male-male tolerance, and facilitated the stepwise aggregation from independent one-male groups to large multilevel societies.


Assuntos
Aclimatação , Clima Frio , Evolução Molecular , Presbytini , Evolução Social , Animais , Feminino , Masculino , Aclimatação/genética , Filogenia , Presbytini/genética , Presbytini/fisiologia , Presbytini/psicologia
17.
Opt Lett ; 48(11): 3027-3030, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37262272

RESUMO

The 1.5-µm fiber laser is widely used in the fields of laser lidar, remote sensing, and gas monitoring because of its advantages of being eye-safe and exhibiting low atmospheric transmission loss. However, due to the ∼1-µm amplified spontaneous emission (ASE) of the Er/Yb co-doped fiber (EYDF), it is difficult to improve the laser power. Here, we simulated the effect of the Er3+ concentration and the seed power on ∼1-µm ASE, and fabricated a large mode area EYDF by the modified chemical vapor deposition process. Additionally, a piece of ytterbium-doped fiber was introduced into the master oscillator power amplifier (MOPA) configuration to absorb the generated ∼1-µm ASE simultaneously. Experimental results show that an output power of 345 W with a slope efficiency of 43% at 1535 nm is obtained in an all-fiber configuration, profiting from effective suppression of ∼ 1-µm ASE. To the best of our knowledge, this is the highest output power available with an Er/Yb co-doped fiber from an all-fiber MOPA configuration.

18.
Cell Oncol (Dordr) ; 46(4): 1069-1083, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36930333

RESUMO

PURPOSE: The eukaryotic cell plasma membrane contains several asymmetrically distributed phospholipids, which is maintained by the P4-ATPase flippase complex. Herein, we demonstrated the biological effects and mechanisms of asymmetrical loss in hematopoietic stem cells (HSCs). METHODS: An Atp8a1 knockout mouse model was employed, from which the HSC (long-term HSCs and short-term HSCs) population was analyzed to assess their abundance and function. Additionally, competitive bone marrow transplantation and 5-FU stress assays were performed. RNA sequencing was performed on Hematopoietic Stem and Progenitor Cells, and DNA damage was assayed using immunofluorescence staining and comet electrophoresis. The protein abundance for members of key signaling pathways was confirmed using western blotting. RESULTS: Atp8a1 deletion resulted in slight hyperleukocytosis, associated with the high proliferation of HSCs and BCR/ABL1 transformed leukemia stem cells (LSCs). Atp8a1 deletion increased the repopulation capability of HSCs with a competitive advantage in reconstitution assay. HSCs without Atp8a1 were more sensitive to 5-FU-induced apoptosis. Moreover, Atp8a1 deletion prevented HSC DNA damage and facilitated DNA repair processes. Genes involved in PI3K-AKT-mTORC1, DNA repair, and AP-1 complex signaling were enriched and elevated in HSCs with Atp8a1 deletion. Furthermore, Atp8a1 deletion caused decreased PTEN protein levels, resulting in the activation of PI3K-AKT-mTORC1 signaling, further increasing the activity of JNK/AP-1 signaling and YAP1 phosphorylation. CONCLUSION: We identified the role of Atp8a1 on hematopoiesis and HSCs. Atp8a1 deletion resulted in the loss of phosphatidylserine asymmetry and intracellular signal transduction chaos.


Assuntos
PTEN Fosfo-Hidrolase , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fator de Transcrição AP-1/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fluoruracila , Adenosina Trifosfatases/metabolismo , Proteínas de Transferência de Fosfolipídeos/metabolismo
19.
Signal Transduct Target Ther ; 8(1): 90, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36854750

RESUMO

We report herein that TSPAN32 is a key node factor for Philadelphia (Ph+) leukemia pathogenesis. We found that TSPAN32 expression was repressed by BCR-ABL and ectopic TSPAN32 expression upon Imatinib treatment inhibited the proliferation of Ph+ cell lines. Tspan32 overexpression significantly prevented BCR-ABL induced leukemia progression in a murine model and impaired leukemia stem cell (LSC) proliferation. LSCs represent an obstacle for chronic myeloid leukemia (CML) elimination, which continually replenish leukemia cells and are associated with disease relapse. Therefore, the identification of essential targets that contribute to the survival and self-renewal of LSCs is important for novel curative CML. Mechanistically, TSPAN32 was shown to interact with PTEN, increased its protein level and caused a reduction in PI3K-AKT signaling activity. We also found that TSPAN32 was repressed by BCR-ABL via the suppression of an important transcription factor, TAL1. Ectopic expression of TAL1 significantly increased TSPAN32 mRNA and protein level, which indicated that BCR-ABL repressed TSPAN32 transcription by decreasing TAL1 expression. Overall, we identified a new signaling axis composed of "BCR-ABL-TAL1-TSPAN32-PTEN-PI3K-AKT". Our findings further complement the known mechanisms underlying the transformation potential of BCR-ABL in CML pathogenesis. This new signaling axis also provides a potential means to target PI3K-AKT for CML treatment.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , PTEN Fosfo-Hidrolase , Tetraspaninas , Animais , Camundongos , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Tetraspaninas/metabolismo
20.
Science ; 379(6634): 840-847, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36821675

RESUMO

The annual regrowth of deer antlers provides a valuable model for studying organ regeneration in mammals. We describe a single-cell atlas of antler regrowth. The earliest-stage antler initiators were mesenchymal cells that express the paired related homeobox 1 gene (PRRX1+ mesenchymal cells). We also identified a population of "antler blastema progenitor cells" (ABPCs) that developed from the PRRX1+ mesenchymal cells and directed the antler regeneration process. Cross-species comparisons identified ABPCs in several mammalian blastema. In vivo and in vitro ABPCs displayed strong self-renewal ability and could generate osteochondral lineage cells. Last, we observed a spatially well-structured pattern of cellular and gene expression in antler growth center during the peak growth stage, revealing the cellular mechanisms involved in rapid antler elongation.


Assuntos
Chifres de Veado , Cervos , Células-Tronco Mesenquimais , Regeneração , Animais , Chifres de Veado/citologia , Chifres de Veado/fisiologia , Cervos/fisiologia , Células-Tronco Mesenquimais/fisiologia , Análise de Célula Única , Proteínas de Homeodomínio/metabolismo
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