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1.
Transl Oncol ; 45: 101968, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38713923

RESUMO

OBJECTIVES: Killer cell lectin like receptor G1 (KLRG1) is identified as a co-inhibitory receptor for NK cells and antigen-experienced T cells. The role of KLRG1 in immune regulation in patients with non-small cell lung cancer (NSCLC) remains poorly understood. MATERIALS AND METHODS: We measured the proportion and immune function of KLRG1+CD8+T cells derived from peripheral blood in patients with NSCLC by flow cytometry. Besides, using data from the gene expression profiles and single-cell sequencing, we explored the expression and immune role of KLRG1 in tumor tissues of patients with NSCLC. We further determined the prognostic value of KLRG1 in terms of overall survival (OS) in NSCLC patients. RESULTS: We found that the proportion of KLRG1+CD8+T cells in peripheral blood significantly increased in patients with NSCLC as compared to those with benign pulmonary nodules and healthy donors. Peripheral KLRG1+CD8+T cell proportion was increased in elder subjects compared to that in younger ones, implying an immunosenescence phenotype. Moreover, the KLRG1+CD8+T cell levels were positively correlated with tumor size and TNM stage in the NSCLC cohort. In vitro stimulation experiments demonstrated that the KLRG1+CD8+T cells from peripheral blood expressed higher levels of Granzyme B and perforin than the KLRG1-CD8+ T cells. However, single-cell RNA sequencing data revealed that the KLRG1+CD8+ T cells were less infiltrated in tumor microenvironment and exhibited impaired cytotoxicity. The KLRG1 gene expression levels were significantly lower in tumor tissues than that in normal lung tissues, and were inversely correlated with CDH1 expression levels. Moreover, higher expression of CDH1 in tumor tissues predicted worse overall survival only in patients with KLRG1-high expression, but not in the KLRG1-low subset. CONCLUSION: This study demonstrates that KLRG1+CD8+T cells were associated with tumor immune evasion in NSCLC and suggests KLRG1 as a potential immunotherapy target.

2.
Chemistry ; : e202400741, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38745544

RESUMO

To address key concerns on solid-state pyrene-based luminescent materials, we propose a novel and efficient mechanical bond strategy. This strategy results in a transformation from aggregation-caused quenching (ACQ) to aggregation-induced emission (AIE) effect and a remarkable enhancement of pyrene emission in the solid state. More importantly, an unusual purification of emission is also achieved. Through computational calculation and experimental characterization, finally determined by X-ray diffraction analysis, we prove that the excellent emissions result from the refined molecular arrangements, including reduced π-π stacking, well-ordered packing and enhanced structural stability. This work demonstrates the potential of mechanical bond in the field of organic luminescent molecules, providing a new avenue for developing high-performance organic luminescent materials and beyond.

3.
J Mol Cell Biol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719542

RESUMO

Defects in the FAcilitates Chromatin Transcription (FACT) complex, a histone chaperone composed of SSRP1 and SUPT16H, are implicated in intellectual disability. Here, we reveal that the FACT complex promotes glycolysis and sustains the correct cell fate of neural stem cells/neuroblasts in the Drosophila 3rd instar larval central brain. We show that the FACT complex binds to the promoter region of the estrogen-related receptor (ERR) gene and positively regulates ERR expression. ERR is known to act as an aerobic glycolytic switch by upregulating the enzymes required for glycolysis. Dysfunction of the FACT complex leads to the downregulation of ERR transcription, resulting in a decreased ratio of glycolysis to oxidative phosphorylation (G/O) in neuroblasts. Consequently, neuroblasts exhibit smaller cell sizes, lower proliferation potential, and altered cell fates. Overexpression of ERR or suppression of mitochondrial oxidative phosphorylation in neuroblasts increases the relative G/O ratio and rescues defective phenotypes caused by dysfunction of the FACT complex. Thus, the G/O ratio, mediated by the FACT complex, plays a crucial role in neuroblast cell fate maintenance. Our study may shed light on the mechanism by which mutations in the FACT complex lead to intellectual disability in humans.

4.
FASEB J ; 38(9): e23654, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38717442

RESUMO

Heart failure and cardiac remodeling are both characterized by mitochondrial dysfunction. Healthy mitochondria are required for adequate contractile activity and appropriate regulation of cell survival. In the mammalian heart, enhancement of the mitochondrial unfolded protein response (UPRmt) is cardioprotective under pressure overload conditions. We explored the UPRmt and the underlying regulatory mechanism in terms of hypertension-induced cardiac remodeling and the cardioprotective effect of metformin. Male spontaneously hypertensive rats and angiotensin II-treated neonatal rat cardiomyocytes were used to induce cardiac hypertrophy. The results showed that hypertension induced the formation of aberrant mitochondria, characterized by a reduced mtDNA/nDNA ratio and swelling, as well as lower levels of mitochondrial complexes I to V and inhibition of the expression of one protein subunit of each of complexes I to IV. Such changes eventually enlarged cardiomyocytes and increased cardiac fibrosis. Metformin treatment increased the mtDNA/nDNA ratio and regulated the UPRmt, as indicated by increased expression of activating transcription factor 5, Lon protease 1, and heat shock protein 60, and decreased expression of C/EBP homologous protein. Thus, metformin improved mitochondrial ultrastructure and function in spontaneously hypertensive rats. In vitro analyses revealed that metformin reduced the high levels of angiotensin II-induced mitochondrial reactive oxygen species in such animals and stimulated nuclear translocation of heat shock factor 1 (HSF1). Moreover, HSF1 small-interfering RNA reduced the metformin-mediated improvements in mitochondrial morphology and the UPRmt by suppressing hypertrophic signals and cardiomyocyte apoptosis. These results suggest that HSF1/UPRmt signaling contributes to the beneficial effects of metformin. Metformin-mediated targeting of mitochondrial protein homeostasis and modulation of HSF1 levels have potential therapeutic implications in terms of cardiac remodeling.


Assuntos
Fatores de Transcrição de Choque Térmico , Metformina , Miócitos Cardíacos , Ratos Endogâmicos SHR , Resposta a Proteínas não Dobradas , Animais , Metformina/farmacologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Masculino , Ratos , Fatores de Transcrição de Choque Térmico/metabolismo , Fatores de Transcrição de Choque Térmico/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Hipertensão/metabolismo , Hipertensão/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Angiotensina II/farmacologia , Cardiomegalia/metabolismo , Cardiomegalia/tratamento farmacológico , Cardiomegalia/patologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Ratos Endogâmicos WKY
5.
Inorg Chem ; 63(19): 8958-8969, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38687123

RESUMO

Atomically precise Ag4Ni2 nanoclusters with 2,4-dimethylbenzenethiol as the ligands were synthesized and characterized as a cocatalyst of SiC for the selective hydrogenation of nitroarenes to arylamine in the presence of NaBH4. The obtained Ag4Ni2/SiC samples exhibited extraordinary catalytic activity, and a self-accelerated catalytic process was observed with the reduction of nitrophenol to aminophenol as the model reaction. Experimental comparison between the Ag4Ni2/SiC samples before and after the catalysis showed that the transformation of Ag4Ni2 clusters to polydisperse Ag particles as well as amorphous NiOx on the surface of SiC in the catalysis was the key to their high activity. AIMD calculations revealed that the transformation of Ag4Ni2 was driven by the presence of multiple hydrides on the cluster, which induced the detachment of the thiol ligand of the nanoclusters.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38656569

RESUMO

Hair follicle stem cells (HFSCs) are adult stem cells located in the outer root sheath of the follicle bulge with high neural plasticity, which promise a potential for the stem cell therapy for neurological diseases. Hirschsprung's disease (HD) is characterized by the absence of ganglia in the distant bowel. In this study, we elucidated the capacity of HFSCs to differentiate into neuronal cells in the aganglionic colon from embryonic rat. HFSCs were isolated from adult Sprague-Dawley (SD) rats and formed spheres that could be passaged. The cultured HFSCs expressed neural crest stem cells (NCSCs) markers such as SOX10, CD34, and nestin, which indicated their neural crest lineage. Subsequent differentiation assays demonstrated that these cells could give rise to neural progeny that expressed neuronal or glial markers. The aganglionic colon from the embryonic intestine was applied as in vitro explant to test the capacity of proliferation and differentiation of HFSCs. The HFSCs expressing GFP or RFP integrated in intestinal explants and maintained proliferative capacity. Moreover, the HFSCs differentiated into Tuj1- or S100ß-positive cells in the cultured intestinal explants. The results proposed that the HFSCs might be an alternative source of neural stem cells for the HD therapy.

7.
Nat Commun ; 15(1): 3432, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653778

RESUMO

Temporal regulation of super-enhancer (SE) driven transcription factors (TFs) underlies normal developmental programs. Neuroblastoma (NB) arises from an inability of sympathoadrenal progenitors to exit a self-renewal program and terminally differentiate. To identify SEs driving TF regulators, we use all-trans retinoic acid (ATRA) to induce NB growth arrest and differentiation. Time-course H3K27ac ChIP-seq and RNA-seq reveal ATRA coordinated SE waves. SEs that decrease with ATRA link to stem cell development (MYCN, GATA3, SOX11). CRISPR-Cas9 and siRNA verify SOX11 dependency, in vitro and in vivo. Silencing the SOX11 SE using dCAS9-KRAB decreases SOX11 mRNA and inhibits cell growth. Other TFs activate in sequential waves at 2, 4 and 8 days of ATRA treatment that regulate neural development (GATA2 and SOX4). Silencing the gained SOX4 SE using dCAS9-KRAB decreases SOX4 expression and attenuates ATRA-induced differentiation genes. Our study identifies oncogenic lineage drivers of NB self-renewal and TFs critical for implementing a differentiation program.


Assuntos
Diferenciação Celular , Regulação Neoplásica da Expressão Gênica , Neuroblastoma , Fatores de Transcrição SOXC , Tretinoína , Neuroblastoma/metabolismo , Neuroblastoma/genética , Neuroblastoma/patologia , Tretinoína/farmacologia , Tretinoína/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Fatores de Transcrição SOXC/metabolismo , Fatores de Transcrição SOXC/genética , Humanos , Animais , Linhagem Celular Tumoral , Camundongos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Autorrenovação Celular/efeitos dos fármacos , Autorrenovação Celular/genética , Fator de Transcrição GATA3/metabolismo , Fator de Transcrição GATA3/genética , Linhagem da Célula/genética , Fator de Transcrição GATA2/metabolismo , Fator de Transcrição GATA2/genética , Sistemas CRISPR-Cas , Proteína Proto-Oncogênica N-Myc/metabolismo , Proteína Proto-Oncogênica N-Myc/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética
8.
BMC Pregnancy Childbirth ; 24(1): 268, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605288

RESUMO

BACKGROUND: Although acetaminophen is widely used in women during pregnancy, its safety has not been clearly stated. The study aimed to investigate the association between acetaminophen use and adverse pregnancy outcomes in pregnant women in China. METHODS: We conducted a retrospective cohort study by collecting data on pregnant women who delivered in the Beijing Obstetrics and Gynecology Hospital from January 2018 to September 2023. An acetaminophen use group and a control group were formed based on prenatal exposure to acetaminophen. The pregnancy outcomes that we focused on were stillbirth, miscarriage, preterm birth, APGAR score, birth weight, and congenital disabilities. Pregnant women exposed to acetaminophen were matched to unexposed in a 1:1 ratio with propensity score matching, using the greedy matching macro. SPSS software was used for statistical analysis. Multivariable logistics regression was used to assess the association between acetaminophen use during pregnancy and adverse pregnancy outcomes. RESULTS: A total of 41,440 pregnant women were included, of whom 501 were exposed to acetaminophen during pregnancy, and 40,939 were not exposed. After the propensity score matching, the acetaminophen use and control groups consisted of 501 pregnant women each. The primary analysis showed that acetaminophen exposure during pregnancy was associated with an increased risk of stillbirth (adjusted OR (aOR) = 2.29, 95% CI, 1.19-4.43), APGAR score < 7 at 1 min (aOR = 3.28, 95% CI, 1.73-6.21), APGAR score < 7 at 5 min (aOR = 3.54, 95% CI, 1.74-7.20), APGAR score < 7 at 10 min (aOR = 3.18, 95% CI, 1.58-6.41), and high birth weight (HBW) (aOR = 1.75, 95% CI, 1.05-2.92). Drug exposure during the first and second trimesters increased the odds of stillbirth, miscarriage, APGAR < 7, and the occurrence of at least one adverse pregnancy outcome. In addition, the frequency of drug use more than two times was associated with a higher risk of preterm birth and APGAR score < 7. CONCLUSIONS: Exposure to acetaminophen during pregnancy was significantly associated with the occurrence of adverse pregnancy outcomes, particularly exposure in the first and second trimesters and frequency of use more than twice. It is suggested that acetaminophen should be prescribed with caution in pregnant women.


Assuntos
Aborto Espontâneo , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Gestantes , Natimorto/epidemiologia , Peso ao Nascer , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Acetaminofen/efeitos adversos , Estudos Retrospectivos , Aborto Espontâneo/induzido quimicamente , Aborto Espontâneo/epidemiologia , Pontuação de Propensão , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia
9.
Front Plant Sci ; 15: 1356922, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628367

RESUMO

Among the bioactive compounds, lipid-soluble tanshinone is present in Salvia miltiorrhiza, a medicinal plant species. While it is known that ethephon has the ability to inhibit the tanshinones biosynthesis in the S. miltiorrhiza hairy root, however the underlying regulatory mechanism remains obscure. In this study, using the transcriptome dataset of the S. miltiorrhiza hairy root induced by ethephon, an ethylene-responsive transcriptional factor EIN3-like 1 (SmEIL1) was identified. The SmEIL1 protein was found to be localized in the nuclei, and confirmed by the transient transformation observed in tobacco leaves. The overexpression of SmEIL1 was able to inhibit the tanshinones accumulation to a large degree, as well as down-regulate tanshinones biosynthetic genes including SmGGPPS1, SmHMGR1, SmHMGS1, SmCPS1, SmKSL1 and SmCYP76AH1. These are well recognized participants in the tanshinones biosynthesis pathway. Further investigation on the SmEIL1 was observed to inhibit the transcription of the CPS1 gene by the Dual-Luciferase (Dual-LUC) and yeast one-hybrid (Y1H) assays. The data in this work will be of value regarding the involvement of EILs in regulating the biosynthesis of tanshinones and lay the foundation for the metabolic engineering of bioactive ingredients in S. miltiorrhiza.

10.
Clin Cancer Res ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630555

RESUMO

PURPOSE: Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) indicated for the treatment of EGFR mutated (EGFRm)-driven lung adenocarcinomas. Osimertinib significantly improves progression-free survival in first-line treated patients with EGFRm advanced NSCLC. Despite the durable disease control, the majority of patients receiving osimertinib eventually develop disease progression. EXPERIMENTAL DESIGN: ctDNA profiling analysis on-progression plasma samples from patients treated with osimertinib in both first (Phase 3, FLAURA trial) and second-line trials (Phase 3, AURA3 trial) revealed a high prevalence of PIK3CA/AKT/PTEN alterations. In vitro and in vivo evidence using CRISPR engineered NSCLC cell lines and PXD models support a functional role for PIK3CA and PTEN mutations in the development of osimertinib resistance. RESULTS: These alterations are functionally relevant as EGFRm NSCLC cells with engineered PIK3CA/AKT/PTEN alterations develop resistance to osimertinib and can be re-sensitized by treatment with the combination of osimertinib and the AKT inhibitor capivasertib. Moreover, xenograft and PDX in vivo models with PIK3CA/AKT/PTEN alterations display limited sensitivity to osimertinib relative to models without alteration, and in these double mutant models capivasertib and osimertinib combination elicits an improved anti-tumor effect versus osimertinib alone. CONCLUSIONS: Together, this approach offers a potential treatment strategy for patients with EGFRm-driven NSCLC that have a sub-optimal response, or develop resistance, to osimertinib through PIK3CA/AKT/PTEN alterations.

11.
J Agric Food Chem ; 72(17): 9984-9993, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38635942

RESUMO

Squalene is a high-value antioxidant with many commercial applications. The use of microbial cell factories to produce squalene as an alternative to plant and animal extracts could meet increasing market demand. Yarrowia lipolytica is an excellent host for squalene production due to its high levels of acetyl-CoA and a hydrophobic environment. However, the need for precise and complicated gene editing has hindered the industrialization of this strain. Herein, the rapid construction of a strain with high squalene production was achieved by enhancing the homologous recombination efficiency in Y. lipolytica. First, remodeling of the homologous recombination efficiency resulted in a 10-fold increase in the homologous recombination rate. Next, the whole mevalonate pathway was integrated into the chromosome to enhance squalene production. Then, a higher level of squalene accumulation was achieved by increasing the level of acetyl coenzyme A and regulating the downstream steroid synthesis pathway. Finally, the squalene production reached 35 g/L after optimizing the fermentation conditions and performing a fed-batch culture in a 5 L jar fermenter. This is the highest squalene production ever reported to date by de novo biosynthesis without adding any inhibitors, paving a new path toward the industrial production of squalene and its downstream products.


Assuntos
Recombinação Homóloga , Engenharia Metabólica , Esqualeno , Yarrowia , Yarrowia/metabolismo , Yarrowia/genética , Esqualeno/metabolismo , Fermentação , Ácido Mevalônico/metabolismo
12.
Biomed Pharmacother ; 174: 116589, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38636400

RESUMO

Diabetic cardiomyopathy (DCM) is a common severe complication of diabetes that occurs independently of hypertension, coronary artery disease, and valvular cardiomyopathy, eventually leading to heart failure. Previous studies have reported that Tectorigenin (TEC) possesses extensive anti-inflammatory and anti-oxidative stress properties. In this present study, the impact of TEC on diabetic cardiomyopathy was examined. The model of DCM in mice was established with the combination of a high-fat diet and STZ treatment. Remarkably, TEC treatment significantly attenuated cardiac fibrosis and improved cardiac dysfunction. Concurrently, TEC was also found to mitigate hyperglycemia and hyperlipidemia in the DCM mouse. At the molecular level, TEC is involved in the activation of AMPK, both in vitro and in vivo, by enhancing its phosphorylation. This is achieved through the regulation of endothelial-mesenchymal transition via the AMPK/TGFß/Smad3 pathway. Furthermore, it was demonstrated that the level of ubiquitination of the adiponectin receptor 1 (AdipoR1) protein is associated with TEC-mediated improvement of cardiac dysfunction in DCM mice. Notably the substantial reduction of myocardial fibrosis. In conclusion, TEC improves cardiac fibrosis in DCM mice by modulating the AdipoR1/AMPK signaling pathway. These findings suggest that TEC could be an effective therapeutic agent for the treatment of diabetic cardiomyopathy.


Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Isoflavonas , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/etiologia , Dieta Hiperlipídica/efeitos adversos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose/tratamento farmacológico , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Miocárdio/metabolismo , Receptores de Adiponectina/efeitos dos fármacos , Receptores de Adiponectina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/metabolismo , Estreptozocina
13.
Clin Chim Acta ; 557: 117877, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38537675

RESUMO

This study focuses on recent advances in proteomics and provides an up-to-date use of this technology in identifying cardiovascular disease (CVD) biomarkers. A total of eight electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang, Vip, Sinomed, and CNKI) were searched and five were used for integrative analysis of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR) and 1 secondary indicator area under the curve (AUC). This systematic review and integrative analysis summarized potential biomarkers previously identified by proteomics. The integrative analysis suggested that proteomics technology had high clinical value in CVD diagnosis. The findings provided new possible directions for the prevention or diagnosis of CVD.


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/diagnóstico , Proteômica , Biomarcadores , Sensibilidade e Especificidade , Curva ROC
14.
Huan Jing Ke Xue ; 45(2): 974-982, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471935

RESUMO

The aim of this study was to examine the effects of different modifiers on the changes in aggregates and organic carbon in acidic purple soil, providing a scientific basis for the remediation of acidic purple soil. Using purple soil as the research object, a total of six treatments were set up, including no fertilization (CK), single fertilization (F), fertilization with lime (SF), fertilization with organic fertilizer (OM), fertilization with biochar (BF), and fertilization with distiller's grains ash (JZ). We compared the composition of aggregates in acidic purple soil under the application of different modifiers, as well as the distribution pattern of organic carbon in aggregates of different particle sizes. Combined with the stability indicators of aggregates, we sought to clarify the impact of different modifiers on the structure of aggregates in acidic purple soil. The results showed that fertilization significantly increased the soil pH, with the JZ treatment being the most effective. Fertilization significantly increased soil organic matter content, with the OM treatment showing the largest increase. The BF and OM treatments significantly reduced soil bulk density, whereas the SF and BF treatments significantly increased soil moisture content (P < 0.05). All treatments used < 0.25 mm aggregates as the dominant particle size. Fertilization could significantly increase the content of large aggregates (aggregate structure units with diameter > 0.25 mm). At the same time, fertilization treatments significantly increased the soil geometric mean diameter (GMD), average weight diameter (MWD), and R0.25 value ( > 0.25 mm aggregate content) and reduced the fractal cone number (D) and aggregate destruction rate (PAD) values (P < 0.05). Fertilization also promoted the aggregation and stability of soil aggregates, with the OM treatment having the greatest effect. Compared with that in the CK treatment, fertilization could significantly increase soil organic carbon content by 31.71%-209.67%, with the OM treatment showing the most significant change. Different treatments of soil organic carbon were mainly distributed in large aggregates. Compared with that in the CK treatment, each treatment significantly increased the contribution rate of organic carbon in large aggregates by 19.34%-47.76%, with the OM treatment having the most significant effect (P < 0.05). In general, chemical fertilizer combined with organic fertilizer could promote the formation of large aggregates in acidic purple soil, improve the stability of soil aggregates, and increase the content of soil organic carbon, which is an effective measure to improve the soil structure and improve the quality of acidic purple soil.

15.
Sensors (Basel) ; 24(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38474909

RESUMO

Simultaneous Localization and Mapping (SLAM), as one of the core technologies in intelligent robotics, has gained substantial attention in recent years. Addressing the limitations of SLAM systems in dynamic environments, this research proposes a system specifically designed for plant factory transportation environments, named GY-SLAM. GY-SLAM incorporates a lightweight target detection network, GY, based on YOLOv5, which utilizes GhostNet as the backbone network. This integration is further enhanced with CoordConv coordinate convolution, CARAFE up-sampling operators, and the SE attention mechanism, leading to simultaneous improvements in detection accuracy and model complexity reduction. While mAP@0.5 increased by 0.514% to 95.364, the model simultaneously reduced the number of parameters by 43.976%, computational cost by 46.488%, and model size by 41.752%. Additionally, the system constructs pure static octree maps and grid maps. Tests conducted on the TUM dataset and a proprietary dataset demonstrate that GY-SLAM significantly outperforms ORB-SLAM3 in dynamic scenarios in terms of system localization accuracy and robustness. It shows a remarkable 92.59% improvement in RMSE for Absolute Trajectory Error (ATE), along with a 93.11% improvement in RMSE for the translational drift of Relative Pose Error (RPE) and a 92.89% improvement in RMSE for the rotational drift of RPE. Compared to YOLOv5s, the GY model brings a 41.5944% improvement in detection speed and a 17.7975% increase in SLAM operation speed to the system, indicating strong competitiveness and real-time capabilities. These results validate the effectiveness of GY-SLAM in dynamic environments and provide substantial support for the automation of logistics tasks by robots in specific contexts.

16.
PLoS Biol ; 22(3): e3002240, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38547242

RESUMO

MYCN activates canonical MYC targets involved in ribosome biogenesis, protein synthesis, and represses neuronal differentiation genes to drive oncogenesis in neuroblastoma (NB). How MYCN orchestrates global gene expression remains incompletely understood. Our study finds that MYCN binds promoters to up-regulate canonical MYC targets but binds to both enhancers and promoters to repress differentiation genes. MYCN binding also increases H3K4me3 and H3K27ac on canonical MYC target promoters and decreases H3K27ac on neuronal differentiation gene enhancers and promoters. WDR5 facilitates MYCN promoter binding to activate canonical MYC target genes, whereas MYCN recruits G9a to enhancers to repress neuronal differentiation genes. Targeting both MYCN's active and repressive transcriptional activities using both WDR5 and G9a inhibitors synergistically suppresses NB growth. We demonstrate that MYCN cooperates with WDR5 and G9a to orchestrate global gene transcription. The targeting of both these cofactors is a novel therapeutic strategy to indirectly target the oncogenic activity of MYCN.


Assuntos
Transformação Celular Neoplásica , Proteínas Nucleares , Humanos , Proteínas Nucleares/metabolismo , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Histona Metiltransferases/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Transcrição Gênica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
17.
Chem Soc Rev ; 53(8): 3687-3713, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38411997

RESUMO

The cornerstones of the advancement of flexible optoelectronics are the design, preparation, and utilization of novel materials with favorable mechanical and advanced optoelectronic properties. Molecular crystalline materials have emerged as a class of underexplored yet promising materials due to the reduced grain boundaries and defects anticipated to provide enhanced photoelectric characteristics. An inherent drawback that has precluded wider implementation of molecular crystals thus far, however, has been their brittleness, which renders them incapable of ensuring mechanical compliance required for even simple elastic or plastic deformation of the device. It is perplexing that despite a plethora of reports that have in the meantime become available underpinning the flexibility of molecular crystals, the "discovery" of elastically or plastically deformable crystals remains limited to cases of serendipitous and laborious trial-and-error approaches, a situation that calls for a systematic and thorough assessment of these properties and their correlation with the structure. This review provides a comprehensive and concise overview of the current understanding of the origins of crystal flexibility, the working mechanisms of deformations such as plastic and elastic bending behaviors, and insights into the examples of flexible molecular crystals, specifically concerning photoelectronic changes that occur in deformed crystals. We hope this summary will provide a reference for future experimental and computational efforts with flexible molecular crystals aimed towards improving their mechanical behavior and optoelectronic properties, ultimately intending to advance the flexible optoelectronic technology.

18.
Chemosphere ; 352: 141430, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342149

RESUMO

As a cotton defoliator, tribufos (S,S,S-tributyl phosphorotrithioate) is widespread in the environment. It can cause neurotoxicity in chickens, reproductive toxicity in rats, and can also cause headaches and nausea in humans. However, little is known about its impact on the reproduction of birds. Here, by analyzing the differences in reproductive indexs and histopathological characteristics, we investigated the chronic effects of 32 mg a.i./kg, 160 mg a.i./kg and 800 mg a.i./kg tribufos treatment on the reproductive ability of Japanese quail (Coturnix japonica). The results indicated that 32 mg a.i./kg and 160 mg a.i./kg tribufos treatment significantly reduced the food intake of quails, significantly increased the broken egg rate, and had adverse effects on gonads and liver tissue. The 160 mg a.i./kg tribufos treatment also significantly reduced the average egg production. Moreover, 800 mg a.i./kg treatment had significant negative effects on feed intake (FI), body weight (BW), eggshell thickness, egg production (EP), fertilization rate, hatchability and progeny 14-d survival rate, and it also significantly increased the broken egg rate. In addition, tribufos exposure caused lesions in quail gonads and liver tissue. Overall, our results revealed that tribufos had adverse effects on the reproductive ability of Japanese quail, especially at high concentrations.


Assuntos
Galinhas , Coturnix , Organotiofosfatos , Humanos , Animais , Ratos , Reprodução , Gônadas , Codorniz
19.
Sensors (Basel) ; 24(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38400507

RESUMO

There has been a significant shift in research focus in recent years toward laser-induced graphene (LIG), which is a high-performance material with immense potential for use in energy storage, ultrahydrophobic water applications, and electronic devices. In particular, LIG has demonstrated considerable potential in the field of high-precision human motion posture capture using flexible sensing materials. In this study, we investigated the surface morphology evolution and performance of LIG formed by varying the laser energy accumulation times. Further, to capture human motion posture, we evaluated the performance of highly accurate flexible wearable sensors based on LIG. The experimental results showed that the sensors prepared using LIG exhibited exceptional flexibility and mechanical performance when the laser energy accumulation was optimized three times. They exhibited remarkable attributes, such as high sensitivity (~41.4), a low detection limit (0.05%), a rapid time response (response time of ~150 ms; relaxation time of ~100 ms), and excellent response stability even after 2000 s at a strain of 1.0% or 8.0%. These findings unequivocally show that flexible wearable sensors based on LIG have significant potential for capturing human motion posture, wrist pulse rates, and eye blinking patterns. Moreover, the sensors can capture various physiological signals for pilots to provide real-time capturing.


Assuntos
Grafite , Dispositivos Eletrônicos Vestíveis , Humanos , Captura de Movimento , Eletrônica , Lasers
20.
Heliyon ; 10(4): e25695, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38390092

RESUMO

BACKGROUND: In the process of international communication in Chinese Wushu (ICCW), the government controls the orientation, scale, pace. However, the ICCW currently lacks a standardised government capacity structural system, and a detailed study of framework construction may be required to ensure the smooth development of the ICCW. OBJECTIVES: This study aims to clarify these elements and construct a framework for a governmental capacity system for ICCW. METHODS: For this purpose, an expert interview outline was designed, and in-depth interviews were conducted with 61 experts. Using grounded theory in the qualitative research method, NVivo 12 software was used to conduct a three-level coding analysis of the interview text for data processing and analysis. RESULTS: We extracted 58 opening codes and 11 tree nodes and categorised them into three core categories: supply side government capacity, environment-side government capacity, and demand-side government capacity, accounting for 62.36 %, 24.76 %, and 12.86 % of the total, respectively, which jointly constructed the framework structure system of the governmental capacity system for the ICCW. CONCLUSIONS: This study found that these three-dimensional government capacities have synergistic effects and that multiple measures work together. The government should ensure the supply side's direct promotion effect; the environmental side's indirect influencing effect; and the demand side's internal driving effect to promote ICCW. Meanwhile, a closed-loop systematic study of communication processes should be conducted in combination with communication organisations and individuals.

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