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1.
J Med Chem ; 67(19): 17472-17496, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39311818

RESUMO

Chronic kidney disease (CKD) is a condition characterized by functional deterioration with sustained inflammation and progressive fibrosis of the kidneys affecting over 800 million people worldwide. The P2X7 receptor (P2X7R) plays a key role in CKD progression. Our previous P2X7R antagonists demonstrated good efficacy for treating kidney injury but were limited by low oral exposure and short half-life, restricting their application. This study reports the optimization of P2X7R antagonists for better oral pharmacokinetics. The candidate compound 13a with the respective IC50 of 34.86 and 25.28 nM against human and murine P2X7R, administered orally at 10 mg/kg in mice, exhibits a remarkably long half-life of 161.64 h, with a high exposure of 1,163,980.55 µg·h/L. Oral administration of 13a (0.3 or 1.0 mg/kg, twice weekly) significantly reduced renal injury and fibrosis in unilateral ureteral obstruction and adenine diet-induced mice models, highlighting its potential for delaying the progression of CKD.


Assuntos
Progressão da Doença , Antagonistas do Receptor Purinérgico P2X , Receptores Purinérgicos P2X7 , Insuficiência Renal Crônica , Animais , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Antagonistas do Receptor Purinérgico P2X/farmacologia , Antagonistas do Receptor Purinérgico P2X/farmacocinética , Antagonistas do Receptor Purinérgico P2X/química , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Antagonistas do Receptor Purinérgico P2X/síntese química , Humanos , Receptores Purinérgicos P2X7/metabolismo , Administração Oral , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Relação Estrutura-Atividade , Descoberta de Drogas , Meia-Vida
2.
ACS Appl Mater Interfaces ; 16(37): 49563-49573, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39231017

RESUMO

In this work, an efficient and robust hole transport layer (HTL) based on blended poly((9,9-dioctylfluorenyl-2,7-diyl)-alt-(9-(2-ethylhexyl)-carbazole-3,6-diyl)) (PF8Cz) and crosslinkable 3,3'-(9,9-dimethyl-9H-fluorene-2,7-diyl)bis(9-(4-vinylphenyl)-9H-carbazole) (FLCZ-V) is introduced for high-performance and stable blue quantum dot-based light-emitting diodes (QLEDs), wherein FLCZ-V can in situ-crosslink to a continuous network polymer after thermal treatment and the linear polymer PF8CZ becomes intertwined and imprisoned. As a result, the blended HTL shows a high hole mobility (1.27 × 10-4 cm2 V-1 s-1) and gradient HOMO levels (-5.4 eV of PF8CZ and -5.7 eV of FLCZ-V) that can facilitate hole injecting so as to ameliorate the charge balance and, at the same time, achieve better electron-blocking capability that can effectively attenuate HTL decomposition. Meanwhile, the crosslinked blended HTL showed excellent solvent resistance and a high surface energy of 40.34 mN/m, which is favorable to enhance wettability for the deposition of a follow-up layer and attain better interfacial contact. Based on the blended HTL, blue QLEDs were fabricated by both spin-coating and inkjet printing. For the spin-coated blue QLED, a remarkable enhancement of external quantum efficiency (EQE) of 15.5% was achieved. Also, the EQE of the inkjet-printed blue QLED reached 9.2%, which is thus far the best result for the inkjet-printed blue QLED.

3.
Arch Toxicol ; 98(11): 3763-3775, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39192019

RESUMO

Chlorfenapyr is a novel broad-spectrum insecticide derived from natural pyrrole derivatives produced by Streptomyces spp. It acts as a pro-insecticide and is metabolically converted to the active metabolite, tralopyril. Chlorfenapyr poisoning is known for its delayed neurological symptoms and high mortality. Unfortunately, information on the toxicokinetics, metabolism and tissue distribution of chlorfenapyr and tralopyril is still lacking. In this study, the metabolic profile, toxicokinetics and tissue distribution of chlorfenapyr and tralopyril after oral administration at a toxic dose in mice were investigated. Twenty metabolites were identified in plasma, urine and feces, which were mainly formed by dealkylation, oxidative dechlorination and reductive dechlorination. Toxicokinetic results showed that chlorfenapyr was rapidly converted to tralopyril after administration, and the in vivo half-life (t1/2), area under the curve (AUC) and peak concentration (Cmax) values of tralopyril were significantly higher than those of chlorfenapyr (P < 0.05). Tissue distribution experiments confirmed that the metabolite tralopyril had a longer half-life, a lower clearance and a wide distribution in different organs and tissues compared to chlorfenapyr. It was also able to cross the blood-brain barrier, suggesting a potential association with brain lesions. In addition, a sensitive and rapid LC-MS/MS analytical method was established for the detection of chlorfenapyr and tralopyril. In conclusion, this study provided valuable metabolic, toxicokinetic and tissue distribution information, contributing to future risk assessment and forensic identification in cases of chlorfenapyr poisoning. We recommend considering the assessment of tralopyril levels, which may be of greater therapeutic importance in the management of chlorfenapyr poisoning.


Assuntos
Inseticidas , Piretrinas , Toxicocinética , Animais , Distribuição Tecidual , Inseticidas/toxicidade , Inseticidas/farmacocinética , Camundongos , Masculino , Piretrinas/farmacocinética , Piretrinas/toxicidade , Piretrinas/metabolismo , Administração Oral , Meia-Vida , Área Sob a Curva , Fezes/química
4.
Nat Ecol Evol ; 8(10): 1972-1990, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39152328

RESUMO

The evolution of the vertebrate liver is a prime example of the evolution of complex organs, yet the driving genetic factors behind it remain unknown. Here we study the evolutionary genetics of liver by comparing the amphioxus hepatic caecum and the vertebrate liver, as well as examining the functional transition within vertebrates. Using in vivo and in vitro experiments, single-cell/nucleus RNA-seq data and gene knockout experiments, we confirm that the amphioxus hepatic caecum and vertebrate liver are homologous organs and show that the emergence of ohnologues from two rounds of whole-genome duplications greatly contributed to the functional complexity of the vertebrate liver. Two ohnologues, kdr and flt4, play an important role in the development of liver sinusoidal endothelial cells. In addition, we found that liver-related functions such as coagulation and bile production evolved in a step-by-step manner, with gene duplicates playing a crucial role. We reconstructed the genetic footprint of the transfer of haem detoxification from the liver to the spleen during vertebrate evolution. Together, these findings challenge the previous hypothesis that organ evolution is primarily driven by regulatory elements, underscoring the importance of gene duplicates in the emergence and diversification of a complex organ.


Assuntos
Evolução Biológica , Anfioxos , Fígado , Análise de Célula Única , Vertebrados , Animais , Vertebrados/genética , Anfioxos/genética , Ceco
5.
Evol Lett ; 8(4): 494-504, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39100238

RESUMO

Reindeer have long been served as vital subsistence resources for inhabitants of Arctic and subarctic regions owing to their domestication. However, the evolutionary relationships and divergence times among different reindeer populations, genetic traits that distinguish domesticated reindeer, and factors that contribute to their relative docility compared with that of other Cervidae specie, remain unclear. In this study, we sequenced the genomes of 32 individuals from wild and domestic reindeer populations that inhabit Arctic and subarctic regions. We found that reindeer experienced 2 or more independent domestication events characterized by weak artificial selection pressure and limited significant differences in genomic parameters between wild and domestic populations. Alterations in conserved noncoding elements in the reindeer genomes, particularly those associated with nervous system development, may have contributed to their domestication by rendering the nervous system less responsive. Together, our results suggest that inherent species-specific traits, rather than intense artificial selection, may have played a significant role in the relatively docile behavior of reindeer and offer valuable insights into the domestication process of these animals.

6.
J Affect Disord ; 365: 105-111, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153551

RESUMO

BACKGROUND: Observational studies have shown that individual sleep traits habits are potential risk factors for major depression. However, it is not known whether there is a causal relationship between individual sleep traits habits such as continuous sleep duration, short sleep duration, short sleep duration, insomnia, nap during the day, snoring, and major depression. In this study, Mendelian randomization (MR) was used to predict major depressive disorder (MDD) in individuals sleep traits habits. METHODS: Data were obtained from the genome-wide association study (GWAS). Nine MR analysis methods were used: Inverse Variance Weighted (IVW) [fixed effects/multiplicative random effects], simple mode, simple mode, weighted mode, simple median, weighted median, penalised weighted median, and MR-Egger, MR Egger (bootstrap). IVW was used as the main analysis method for the MR analysis of two samples, and the other methods were used as supplements. RESULTS: The results obtained through the IVW method supported a causal relationship between sleep duration and decreased risk of MDD (odds ratio, ORivw: 0.998; 95 % CI: 0.996-0.999, P<0.001). Two-Sample MR, results showed that short sleep duration has a causal effect on the increased risk of MDD (odds ratio, ORivw: 1.179; 95 % CI: 1.108-1.255, P<0.001). However, there were no sufficient evidence supported that long sleep duration has a causal effect on the decreased risk of MDD (odds ratio, ORivw: 0.991; 95 % CI: 0.924-1.062, P = 0.793). A significant causal relationship between insomnia and increased risk of MDD was observed (OR: 1.233; 95 % CI: 1.214-1.253, P<0.001). Interestingly, our study also found that daytime napping has a causal effect on the increased risk of MDD (odds ratio, ORivw: 1.519; 95 % CI: 1.376-1.678, P<0.001). The present results did not show a significant causal relationship between snoring and the risk of MDD (ORivw: 1.000; 95 % CI: 0.998-1.002, P = 0.906). Obstructive sleep apnea (odds ratio, ORivw: 1.021; 95 % CI: 0.972-1.072, P = 0.407) and morning person (odds ratio, ORivw: 1.021; 95 % CI: 0.972-1.072, P = 0.407) have no causal effect on the increased risk of MDD. LIMITATIONS: The study could not ascertain whether there were genetic differences among different ethnicities, nations, and regions, as it only included participants of European ancestry. CONCLUSIONS: In summary, our research provides genetic evidence for the relationship between individual sleep traits (short sleep duration, insomnia, daytime napping) and the increased risk of MDD. Interventions targeting lifestyle factors may reduce the risk of MDD.


Assuntos
Transtorno Depressivo Maior , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Sono , Humanos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/epidemiologia , Sono/genética , Fatores de Risco , Distúrbios do Início e da Manutenção do Sono/genética , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Polimorfismo de Nucleotídeo Único , Masculino , Ronco/genética , Ronco/epidemiologia , Feminino
7.
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.

8.
Sensors (Basel) ; 24(14)2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39066090

RESUMO

SLAM is a critical technology for enabling autonomous navigation and positioning in unmanned vehicles. Traditional visual simultaneous localization and mapping algorithms are built upon the assumption of a static scene, overlooking the impact of dynamic targets within real-world environments. Interference from dynamic targets can significantly degrade the system's localization accuracy or even lead to tracking failure. To address these issues, we propose a dynamic visual SLAM system named BY-SLAM, which is based on BEBLID and semantic information extraction. Initially, the BEBLID descriptor is introduced to describe Oriented FAST feature points, enhancing both feature point matching accuracy and speed. Subsequently, FasterNet replaces the backbone network of YOLOv8s to expedite semantic information extraction. By using the results of DBSCAN clustering object detection, a more refined semantic mask is obtained. Finally, by leveraging the semantic mask and epipolar constraints, dynamic feature points are discerned and eliminated, allowing for the utilization of only static feature points for pose estimation and the construction of a dense 3D map that excludes dynamic targets. Experimental evaluations are conducted on both the TUM RGB-D dataset and real-world scenarios and demonstrate the effectiveness of the proposed algorithm at filtering out dynamic targets within the scenes. On average, the localization accuracy for the TUM RGB-D dataset improves by 95.53% compared to ORB-SLAM3. Comparative analyses against classical dynamic SLAM systems further corroborate the improvement in localization accuracy, map readability, and robustness achieved by BY-SLAM.

9.
J Agric Food Chem ; 72(29): 16334-16346, 2024 Jul 24.
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.


Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Linfoma não Hodgkin , Polissacarídeos , Humanos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Linfoma não Hodgkin/tratamento farmacológico , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Peso Molecular , Basidiomycota/química
10.
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.

11.
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.

12.
Sci China Life Sci ; 67(9): 2003-2015, 2024 Sep.
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.


Assuntos
Adaptação Fisiológica , Clima Desértico , Ecossistema , Animais , Adaptação Fisiológica/genética , Roedores/genética , Roedores/fisiologia , Genoma/genética , Genômica , Filogenia , Evolução Molecular
13.
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.

14.
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
15.
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.

16.
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.

17.
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
18.
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
19.
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.

20.
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
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