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1.
Front Public Health ; 12: 1333069, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38803814

RESUMEN

Background: Nutritional anemia is highly prevalent and has triggered a globally recognized public health concern worldwide. Objective: To better understand the prevalence of anemia and the state of nutritional health in developed countries to inform global nutritional health and better manage the disease. Method: We employed the Healthcare Cost and Utilization Project (HCUP)-2020 National Inpatient Health Care Data (NIS), administered by The Agency for Healthcare Research and Quality. Nutritional anemia was diagnosed according to the International Classification of Diseases, 10th Revision (ICD-10). Matching analysis and multivariate regression were used to adjust for patient and hospital characteristics. Controls were obtained by stratifying and matching for age and sex. Results: The 2020 HCUP-NIS database encompassed a survey over 6.4 million hospitalized patients, among which 1,745,350 patients diagnosed with anemia, representing approximately 26.97% of the hospitalized population, over 310,000 were diagnosed with nutritional anemia, and 13,150 patients were hospitalized for nutritional anemia as primary diagnosis. Hospitalization rate for nutritional anemia exhibited an increased age-dependent increase nationwide, especially among females, who displayed 1.87 times higher than males. Notably, in comparison to the control group, individuals of the Black race exhibit a higher prevalence of nutritional anemia (case group: 21.7%, control group: 13.0%, p < 0.001). In addition, hospitalization rates were higher among low-income populations, with lower rates of private insurance (case group: 18.7%, control group: 23.5%, p < 0.001) and higher rates of Medicaid insurance (case group: 15.4%, control group: 13.9%, p < 0.001). In areas characterized by larger urban centers and advanced economic conditions within the urban-rural distribution, there was an observed increase in the frequency of patient hospitalizations. Iron deficiency anemia emerged as the predominant subtype of nutritional anemia, accounting for 12,214 (92.88%). Secondary diagnosis among patients hospitalized for nutritional anemia revealed that a significant number faced concurrent major conditions like hypertension and renal failure. Conclusion: In economically prosperous areas, greater attention should be given to the health of low-income individuals and the older adult. Our findings hold valuable insights for shaping targeted public health policies to effectively address the prevalence and consequences of nutritional anemia based on a overall population health.


Asunto(s)
Anemia , Hospitalización , Humanos , Masculino , Femenino , Estados Unidos/epidemiología , Hospitalización/estadística & datos numéricos , Persona de Mediana Edad , Anemia/epidemiología , Adulto , Anciano , Adolescente , Prevalencia , Adulto Joven , Lactante , Niño , Preescolar , Anciano de 80 o más Años
2.
Materials (Basel) ; 17(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38730741

RESUMEN

In this study, an effective numerical model was developed for the calculation of the deformation of laser-welded 3 mm 304L stainless steel plates with different gaps (0.2 mm, 0.5 mm, and 1.0 mm). The welding deformation would become larger when the welding gaps increased, and the largest deformation values along the Z direction, of 4 mm, were produced when the gap value was 1.0 mm. A larger plastic strain region was generated in the location near the weld seam, since higher plastic deformation had occurred. In addition, the tensile stress model was also applied at the plastic strain zone and demonstrated that a larger welding gap led to a wider residual stress area. Based on the above results, inherent deformations for butt and corner joints were calculated according to inherent strain theory, and the welding formation for the complex structure was calculated with different gaps. The numerical results demonstrated that a larger deformation was also produced with a larger welding gap and that it could reach the highest value of 10.1 mm. This proves that a smaller welding gap should be adopted during the laser welding of complex structures to avoid excessive welding deformation.

3.
Sci Rep ; 14(1): 10621, 2024 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-38729969

RESUMEN

Asymptomatic Leucine-Rich Repeat Kinase 2 Gene (LRRK2) carriers are at risk for developing Parkinson's disease (PD). We studied presymptomatic substantia nigra pars compacta (SNc) regional neurodegeneration in asymptomatic LRRK2 carriers compared to idiopathic PD patients using neuromelanin-sensitive MRI technique (NM-MRI). Fifteen asymptomatic LRRK2 carriers, 22 idiopathic PD patients, and 30 healthy controls (HCs) were scanned using NM-MRI. We computed volume and contrast-to-noise ratio (CNR) derived from the whole SNc and the sensorimotor, associative, and limbic SNc regions. An analysis of covariance was performed to explore the differences of whole and regional NM-MRI values among the groups while controlling the effect of age and sex. In whole SNc, LRRK2 had significantly lower CNR than HCs but non-significantly higher volume and CNR than PD patients, and PD patients significantly lower volume and CNR compared to HCs. Inside SNc regions, there were significant group effects for CNR in all regions and for volumes in the associative region, with a trend in the sensorimotor region but no significant changes in the limbic region. PD had reduced volume and CNR in all regions compared to HCs. Asymptomatic LRRK2 carriers showed globally decreased SNc volume and CNR suggesting early nigral neurodegeneration in these subjects at risk of developing PD.


Asunto(s)
Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Imagen por Resonancia Magnética , Melaninas , Enfermedad de Parkinson , Sustancia Negra , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Melaninas/metabolismo , Imagen por Resonancia Magnética/métodos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/metabolismo , Sustancia Negra/diagnóstico por imagen , Sustancia Negra/patología , Sustancia Negra/metabolismo , Anciano , Heterocigoto , Adulto , Estudios de Casos y Controles
4.
Mater Horiz ; 11(8): 1877-1888, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38516937

RESUMEN

Artificial muscles that can convert electrical energy into mechanical energy promise broad scientific and technological applications. However, existing electro-driven artificial muscles have been plagued with problems that hinder their practical applications: large electro-mechanical attenuation during deformation, high-driving voltages, small actuation strain, and low power density. Here, we design and create novel electro-thermal-driven artificial muscles rationally composited by hierarchically structured carbon nanotube (HS-CNT) networks and liquid crystal elastomers (LCEs), which possess adaptive sandwiched nanotube networks with angulated-scissor-like microstructures, thus effectively addressing above problems. These HS-CNT/LCE artificial muscles demonstrate not only large strain (>40%), but also remarkable conductive robustness (R/R0 < 1.03 under actuation), excellent Joule heating efficiency (≈ 233 °C at 4 V), and high load-bearing capacity (R/R0 < 1.15 at 4000 times its weight loaded). In addition, our artificial muscles exhibit real-muscle-like morphing intelligence that enables preventing mechanical damage in response to excessively heavyweight loading. These high-performance artificial muscles uniquely combining omnidirectional stretchability, robust electrothermal actuation, low driving voltage, and powerful mechanical output would exert significant technological impacts on engineering applications such as soft robotics and wearable flexible electronics.

5.
ACS Omega ; 9(11): 13183-13190, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38524484

RESUMEN

Nitrogen-doped carbon dots (NCD) with high fluorescence retention and good stability were successfully fabricated using citric acid and urea via a facile and eco-friendly one-step microwave method, which exhibited superior specificity for detection of nitrofurantoin (NFT). Upon the addition of NFT, the fluorescence intensity of NCD at 450 nm was significantly decreased. Besides, a satisfactory linear relationship between the fluorescence quenching efficiency and concentrations of NFT was obtained. Especially, NCD was qualitatively and quantitatively applied for detection NFT in milk and meat extract samples with a high recovery rate. Consequently, it was suggested that the detection method had potential application in the specific detection of NFT, offering a novel approach for veterinary drug residue detection.

6.
Pest Manag Sci ; 80(6): 3010-3021, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38318950

RESUMEN

BACKGROUND: Valsa canker caused by Valsa pyri is one of the most destructive diseases of pear, leading to severe yield and economic losses. Volatile organic compounds (VOCs) from endophytes have important roles in the regulation of plant disease. In this study, we investigated the biocontrol activity of the endophytic fungus Aspergillus niger strain La2 and its antagonistic VOCs against pear Valsa canker. RESULTS: Strain La2 exhibited an obvious inhibitory effect against V. pyri. A colonization assay suggested that strain La2 could complete its life cycle on pear twigs. The symptoms of pear Valsa canker were weakened on detached pear twigs after treatment with strain La2. In addition, VOCs from strain La2 also significantly suppressed mycelial growth in V. pyri. Based on the results of headspace solid-phase microextraction/gas chromatography-mass spectrometry analysis, six possible VOCs produced by strain La2 were detected, of which 2,4-di-tert-butylphenol and 4-methyl-1-pentanol were the main antagonistic VOCs in terms of their effect on pear Valsa canker in vitro and in vivo. Further results showed that 4-methyl-1-pentanol could destroy the V. pyri hyphal structure and cell membrane integrity. Importantly, the activities of pear defense-related enzymes (polyphenol oxidase, phenylalanine ammonia lyase and superoxide dismutase) were enhanced after 4-methyl-1-pentanol treatment in pear twigs, suggesting that 4-methyl-1-pentanol might induce a plant disease resistance response. CONCLUSION: Aspergillus niger strain La2 and its VOCs 2,4-di-tert-butylphenol and 4-methyl-1-pentanol have potential as novel biocontrol agents of pear Valsa canker. © 2024 Society of Chemical Industry.


Asunto(s)
Aspergillus niger , Enfermedades de las Plantas , Pyrus , Compuestos Orgánicos Volátiles , Pyrus/microbiología , Compuestos Orgánicos Volátiles/farmacología , Compuestos Orgánicos Volátiles/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Endófitos/fisiología , Agentes de Control Biológico/farmacología
7.
Chemistry ; 30(4): e202303319, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38010959

RESUMEN

With the extensive use of fossil fuels, the ever-increasing greenhouse gas of mainly carbon dioxide emissions will result in global climate change. It is of utmost importance to reduce carbon dioxide emissions and its utilization. Li-CO2 batteries can convert carbon dioxide into electrochemical energy. However, developing efficient catalysts for the decomposition of Li2 CO3 as the discharge product represents a challenge in Li-CO2 batteries. Herein, we demonstrate a carbon foam composite with growing carbon nanotube by using cobalt as the catalyst, showing the ability to enhance the decomposition rate of Li2 CO3 , and thus improve the electrochemical performance of Li-CO2 batteries. Benefiting from its abundant pore structure and catalytic sites, the as-assembled Li-CO2 battery exhibits a desirable overpotential of 1.67 V after 50 cycles. Moreover, the overpotentials are 1.05 and 2.38 V at current densities of 0.02 and 0.20 mA cm-2 , respectively. These results provide a new avenue for the development of efficient catalysts for Li-CO2 batteries.

8.
Luminescence ; 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38038156

RESUMEN

In this work, interaction mechanism of narcissoside with two α-amylase from Bacillus subtilis (BSA) and Porcine pancreatic (PPA) are comparatively studied by multi-spectral analysis, molecular docking and molecular dynamics simulation. The results prove that narcissoside can statically quench fluorescence of BSA/PPA. Two complexes are mainly formed by hydrogen bond and van der Waals force. With the increase of temperature, the two complexes formed by narcissoside and two enzymes become unstable. At the same experimental temperature, the binding force of narcissoside to PPA is higher than that of BSA. The binding of narcissoside to PPA/BSA increases the hydrophobicity of microenvironment. Moreover, the secondary structure of PPA/BSA is mainly changed by decreasing the α-helix. The optimal binding modes of narcissoside with BSA/PPA are predicted by molecular docking, and the stability of the two complexes is evaluated by molecular dynamics simulations.

9.
Cell Death Dis ; 14(11): 728, 2023 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-37945598

RESUMEN

Multiple tumors are synergistically promoted by c-Met and TRK, and blocking their cross-signalling pathway may give better effects. In this study, we developed a tyrosine kinase inhibitor 1D228, which exhibited excellent anti-tumor activity by targeting c-Met and TRK. Models in vitro, 1D228 showed a significant better inhibition on cancer cell proliferation and migration than the positive drug Tepotinib. Models in vivo, 1D228 showed robust anti-tumor effect on gastric and liver tumor growth with 94.8% and 93.4% of the TGI, respectively, comparing 67.61% and 63.9% of Tepotinib. Importantly, compared with the combination of Larotrectinib and Tepotinib, 1D228 monotherapy in MKN45 xenograft tumor models showed stronger antitumor activity and lower toxicity. Mechanistic studies showed that 1D228 can largely inhibit the phosphorylation of TRKB and c-Met. Interestingly, both kinases, TRKs and c-Met, have been found to be co-expressed at high levels in patients with gastric cancer through IHC. Furthermore, bioinformatics analysis has revealed that both genes are abnormally co-expressed in multiple types of cancer. Cell cycle analysis found that 1D228 induced G0/G1 arrest by inhibiting cyclin D1. Additionally, vascular endothelial cells also showed a pronounced response to 1D228 due to its expression of TRKB and c-Met. 1D228 suppressed the migration and tube formation of endothelial cells, which are the key functions of tumor angiogenesis. Taken together, compound 1D228 may be a promising candidate for the next generation of c-Met and TRK inhibitors for cancer treatment, and offers a novel potential treatment strategy for cancer patients with abnormal expressions of c-Met or NTRK, or simultaneous of them.


Asunto(s)
Células Endoteliales , Neoplasias Hepáticas , Humanos , Proliferación Celular , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Luminescence ; 38(9): 1654-1667, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37421260

RESUMEN

The interactions of human CYP3A4 with three selected isomer flavonoids, such as astilbin, isoastilbin and neoastilbin, were clarified using spectral analysis, molecular docking, and molecular dynamics simulation. During binding with the three flavonoids, the intrinsic fluorescence of CYP3A4 was statically quenched in static mode with nonradiative energy conversion. The fluorescence and ultraviolet/visible (UV/vis) data revealed that the three flavonoids had a moderate and stronger binding affinity with CYP3A4 due to the order of the Ka1 and Ka2 values ranging from 104 to 105  L·mol-1 . In addition, astilbin had the highest affinity with CYP3A4, then isoastilbin and neoastilbin, at the three experimental temperatures. Multispectral analysis confirmed that binding of the three flavonoids resulted in clear changes in the secondary structure of CYP3A4. It was found from fluorescence, UV/vis and molecular docking analyses that these three flavonoids strongly bound to CYP3A4 by means of hydrogen bonds and van der Waals forces. The key amino acids around the binding site were also elucidated. Furthermore, the stabilities of the three CYP3A4 complexes were evaluated using molecular dynamics simulation.


Asunto(s)
Citocromo P-450 CYP3A , Flavonoides , Humanos , Simulación del Acoplamiento Molecular , Flavonoides/química , Sitios de Unión , Termodinámica , Unión Proteica , Espectrometría de Fluorescencia/métodos , Dicroismo Circular
11.
Plant Cell ; 35(9): 3485-3503, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37335905

RESUMEN

Ambient light and the endogenous circadian clock play key roles in regulating Arabidopsis (Arabidopsis thaliana) seedling photomorphogenesis. PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) acts downstream of both light and the circadian clock to promote hypocotyl elongation. Several members of the R2R3-MYB transcription factor (TF) family, the most common type of MYB TF family in Arabidopsis, have been shown to be involved in regulating photomorphogenesis. Nonetheless, whether R2R3-MYB TFs are involved in connecting the light and clock signaling pathways during seedling photomorphogenesis remains unknown. Here, we report that MYB112, a member of the R2R3-MYB family, acts as a negative regulator of seedling photomorphogenesis in Arabidopsis. The light signal promotes the transcription and protein accumulation of MYB112. myb112 mutants exhibit short hypocotyls in both constant light and diurnal cycles. MYB112 physically interacts with PIF4 to enhance the transcription of PIF4 target genes involved in the auxin pathway, including YUCCA8 (YUC8), INDOLE-3-ACETIC ACID INDUCIBLE 19 (IAA19), and IAA29. Furthermore, MYB112 directly binds to the promoter of LUX ARRHYTHMO (LUX), the central component of clock oscillators, to repress its expression mainly in the afternoon and relieve LUX-inhibited expression of PIF4. Genetic evidence confirms that LUX acts downstream of MYB112 in regulating hypocotyl elongation. Thus, the enhanced transcript accumulation and transcriptional activation activity of PIF4 by MYB112 additively promotes the expression of auxin-related genes, thereby increasing auxin synthesis and signaling and fine-tuning hypocotyl growth under diurnal cycles.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Relojes Circadianos , Fitocromo , Arabidopsis/metabolismo , Relojes Circadianos/genética , Hipocótilo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Plantones/genética , Fitocromo/genética , Fitocromo/metabolismo , Ácidos Indolacéticos/metabolismo , Regulación de la Expresión Génica de las Plantas , Luz
12.
Bioorg Chem ; 138: 106653, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37302317

RESUMEN

For non-small cell lung cancer patients with dual mutations in EGFR and ALK, there are currently no effective therapies. Consequently, novel EGFR/ALK dual-target inhibitors are urgently needed for the treatment of NSCLC. Here, we designed a series of highly effective small molecule dual inhibitors of ALK and EGFR. The biological evaluation highlighted that most of these new compounds could effectively inhibit both ALK and EGFR in enzymatic and cellular assays. Compound (+)-8l was investigated for its antitumor properties, and it was found that (+)-8l blocked the phosphorylation of EGFR and ALK induced by ligands and inhibited phosphorylation-ERK and phosphorylation-AKT induced by ligands. Furthermore, (+)-8l also induces apoptosis and G0/G1 cell cycle arrest in cancer cells and inhibits proliferation, migration, and invasion. Notably, (+)-8l significantly suppressed tumor growth in the H1975 cell-inoculated xenograft model (20 mg/kg/d, TGI: 96.11%), PC9 cell-inoculated xenograft model (20 mg/kg/d, TGI: 96.61%) and EML4 ALK-Baf3 cell-inoculated xenograft model (30 mg/kg/d, TGI: 80.86%). These results highlight the differentiated potential of (+)-8l to inhibit ALK rearrangement and EGFR mutation in NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Ligandos , Receptores ErbB , Fosforilación , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Línea Celular Tumoral , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo
13.
Front Nutr ; 10: 1144346, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37090774

RESUMEN

Introduction: Lead is a ubiquitous environmental and industrial pollutant. Its nonbiodegradable toxicity induces a plethora of human diseases. A novel bioactive glycoprotein containing 1.15% carbohydrate, with the ability of adsorbing lead and effecting detoxification, has been purified from Auricularia polytricha and designated as APL. Besides, its mechanisms related to regulation of hepatic metabolic derangements at the proteome level were analyzed in this study. Methods: Chromatographic techniques were utilized to purify APL in the current study. For investigating the protective effects of APL, Sprague-Dawley rats were given daily intraperitoneal injections of lead acetate for establishment of an animal model, and different dosages of APL were gastrically irrigated for study of protection from lead detoxification. Liver samples were prepared for proteomic analyses to explore the detoxification mechanisms. Results and discussion: The detoxifying glycoprotein APL displayed unique molecular properties with molecular weight of 252-kDa, was isolated from fruiting bodies of the edible fungus A. polytricha. The serum concentrations of lead and the liver function biomarkers aspartate and alanine aminotransferases were significantly (p<0.05) improved after APL treatment, as well as following treatment with the positive control EDTA (300 mg/kg body weight). Likewise, results on lead residue showed that the clearance ratios of the liver and kidneys were respectively 44.5% and 18.1% at the dosage of APL 160 mg/kg, which was even better than the corresponding data for EDTA. Proteomics disclosed that 351 proteins were differentially expressed following lead exposure and the expression levels of 41 proteins enriched in pathways mainly involved in cell detoxification and immune regulation were normalized after treatment with APL-H. The results signify that APL ameliorates lead-induced hepatic injury by positive regulation of immune processing, and suggest that APL can be applied as a therapeutic intervention of lead poisoning in clinical practice. This report represents the first demonstration of the protective action of a novel mushroom protein on lead-elicited hepatic toxicity.

14.
J Fungi (Basel) ; 9(4)2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-37108868

RESUMEN

Mycelial ageing is associated with ROS and autophagy in Lentinula edodes. However, the underlying cellular and molecular mechanisms between ROS and autophagy remain obscure. This study induced autophagy in L. edodes mycelia through exogenous H2O2 treatment. Results showed that 100 µM H2O2 treatment for 24 h significantly inhibited mycelial growth. H2O2 caused the depolarisation of MMP and accumulation of TUNEL-positive nuclei, which was similar to the ageing phenotype of L. edodes mycelia. Transcriptome analysis showed that differentially expressed genes were enriched in the mitophagic, autophagic, and MAPK pathways. LeAtg8 and LeHog1 were selected as hub genes. RNA and protein levels of LeATG8 increased in the H2O2-treated mycelia. Using fluorescent labelling, we observed for the first time the classic ring structure of autophagosomes in a mushroom, while 3D imaging suggested that these autophagosomes surrounded the nuclei to degrade them at specific growth stages. Phospho-LeHOG1 protein can translocate from the cytoplasm to the nucleus to regulate mycelial cells, resisting ROS-induced oxidative stress. Furthermore, LeATG8 expression was suppressed when LeHOG1 phosphorylation was inhibited. These results suggest that the LeATG8-dependent autophagy in L. edodes mycelial is closely associated with the activity or even phosphorylation of LeHOG1.

15.
Molecules ; 28(5)2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36903251

RESUMEN

ALK-positive NSCLC coexisting with EGFR mutations is a frequently occurring clinical phenomenon. Targeting ALK and EGFR simultaneously may be an effective way to treat these cancer patients. In this study, we designed and synthesized ten new dual-target EGFR/ALK inhibitors. Among them, the optimal compound 9j exhibited good activity with IC50 values of 0.07829 ± 0.03 µM and 0.08183 ± 0.02 µM against H1975 (EGFR T790M/L858R) and H2228 (EML4-ALK) cells, respectively. Immunofluorescence assays indicated that the compound could simultaneously inhibit the expression of phosphorylated EGFR and ALK proteins. A kinase assay demonstrated that compound 9j could inhibit both EGFR and ALK kinases; thus, exerting an antitumor effect. Additionally, compound 9j induced apoptosis in a dose-dependent manner and inhibited the invasion and migration of tumor cells. All of these results indicate that 9j is worthy of further study.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/metabolismo , Proteínas Tirosina Quinasas Receptoras , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Mutación , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Antineoplásicos/farmacología
16.
J Fungi (Basel) ; 9(3)2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36983547

RESUMEN

The spawn of Lentinula edodes and other basidiomycete fungi tend to age with long-term culture. This causes heavy yield losses if aging spawn is used for propagation. In this study, we cultivated dikaryotic L. edodes mycelia in plates for 60 days to produce intrinsic aging phenotypes. We found that intracellular reactive oxygen species levels increased in contrast to mitochondrial depolarization and also observed greater DNA fragmentation with longer culture time. Transcriptome analysis of mycelia at different growth stages revealed pronounced expression differences between short- and long-term cultures. In particular, "phenylalanine, tyrosine, and tryptophan biosynthesis", "mitophagy and autophagy", "MAPK signaling pathway", and "ABC transporter" were among the enriched terms in the mycelial aging process. Weighted correlation network analysis identified LeAtg8, LeHog1, LePbs2, and LemTOR as key genes during aging. Western blotting confirmed that LeATG8 and phosphorylated LeHOG1 protein levels were significantly upregulated in aging mycelia. Our combined analytical approach provides insights into the mechanisms that regulate mycelial aging, indicating that autophagy/mitophagy plays a major role in counteracting the effects of age on mycelial growth development.

17.
J Fungi (Basel) ; 9(2)2023 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-36836294

RESUMEN

Temperature type is one of the key traits determining the cultivation regime of Lentinula edodes. However, the molecular and metabolic basis underling temperature type remain unclear. Here, we investigated the phenotypic, transcriptomic, and metabolic features of L. edodes with different temperature types under both control (25 °C) and high (37 °C) temperature conditions. We found that under the control condition, the high- and low-temperature types of L. edodes harbored distinct transcriptional and metabolic profiles. The high-temperature (H-)-type strain had a higher expression level of genes involved in the toxin processes and carbohydrate binding, while the low-temperature (L-)-type strain had a high expression level of oxidoreductase activity. Heat stress significantly inhibited the growth of both H- and L-type strains, while the latter had a higher growth inhibition rate. Upon exposure to heat, the H-type strain significantly up-regulated genes associated with the components of the cellular membrane, whereas the L-type strain markedly up-regulated genes involved in the extracellular region and carbohydrate binding. Metabolome data showed that thermostress altered purine and pyrimidine metabolism in the H-type strain, whereas it altered cysteine, methionine, and glycerophospholipid metabolism in the L-type strain. Transcriptome and metabolome integrative analysis was able to identify three independent thermotolerance-related gene-metabolite regulatory networks. Our results deepen the current understanding of the molecular and metabolic basis underlying temperature type and suggest, for the first time, that thermotolerance mechanisms can be temperature-type-dependent for L. edodes.

18.
Plant Cell ; 35(2): 700-716, 2023 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-36423345

RESUMEN

Light is a major environmental factor for seed germination. Red light-activated phytochrome B (phyB) promotes seed germination by modulating the dynamic balance of two phytohormones, gibberellic acid (GA) and abscisic acid (ABA). How phyB modulates ABA biosynthesis after perceiving a light signal is not yet well understood. Here, we identified the noncoding RNA HIDDEN TREASURE 1 (HID1) as a repressor of ABA biosynthesis acting downstream of phyB during Arabidopsis thaliana seed germination. Loss of HID1 function led to delayed phyB-dependent seed germination. Photoactivated phyB promoted the accumulation of HID1 in the radicle within 48 h of imbibition. Our transcriptomics analysis showed that HID1 and phyB co-regulate the transcription of a common set of genes involved in ABA and GA metabolism. Through a forward genetic screen, we identified three ABA biosynthesis genes, ABA DEFICIENT 1 (ABA1), ABA2, and ABA3, as suppressors of HID1. We further demonstrated that HID1 directly inhibits the transcription of 9-CIS-EPOXYCAROTENOID DIOXYGENASE (NCED9), a gene encoding a key rate-limiting enzyme of ABA biosynthesis. HID1 interacts with ARABIDOPSIS TRITHORAX-RELATED7 (ATXR7), an H3K4me3 methyltransferase, inhibiting its occupancy and H3K4me3 modification at the NCED9 locus. Our study reveals a nuclear mechanism of phyB signaling transmitted through HID1 to control the internal homeostasis of ABA and GA, which gradually optimizes the transcriptional network during seed germination.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Fitocromo B/genética , Fitocromo B/metabolismo , Proteínas de Arabidopsis/metabolismo , Germinación/genética , Semillas/genética , Semillas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Giberelinas/metabolismo , Regulación de la Expresión Génica de las Plantas/genética
19.
Front Psychiatry ; 14: 1214192, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38179248

RESUMEN

Objective: We aimed to investigate the characteristics and psychological mechanism of non-suicidal self-injury (NSSI) in adolescents with mood disorders. We examined how self-compassion and emotional regulation affected NSSI and tested the mediating role of self-compassion in the link between emotional regulation and NSSI. Method: We recruited outpatient and inpatient adolescent patients with bipolar and related disorders or depressive disorders (DSM-5), with a focus on NSSI. We also recruited healthy controls from the community. We collected demographic and clinical data. The Adolescent Self-injury Questionnaire, Self-compassion Scale (SCS), and Emotion Regulation Questionnaire (ERQ) were used to assess the frequency and severity of NSSI, level of self-compassion, and emotional regulation. Results: In total, we recruited 248 adolescent patients with mood disorders (N = 196 with NSSI, and 52 without NSSI) and 212 healthy controls. NSSI was significantly associated with the female sex, lower levels of education and less use of cognitive reappraisal strategies, lower levels of self-warmth, and higher levels of self-coldness. Multivariate analysis of variance showed that there were significant differences in the scores of ERQ, cognitive reassessment score, and the scores of SCS among the three groups, but no statistical differences in expressive suppression score among the three groups. Self-warmth had a mediating effect between cognitive reappraisal and NSSI behavior. Conclusion: NSSI is prevalent among adolescent patients with mood disorders in clinical settings, especially among girls and those with lower levels of education and less cognitive reappraisal strategies. More clinical attention is needed. Self-compassion and its factors may mediate the association between emotional regulation and NSSI. Clinical implications and future research directions were discussed.

20.
Foods ; 13(1)2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38201114

RESUMEN

For Lentinula edodes, its characteristic flavor is the key determinant for consumer preferences. However, the tissue-specific volatile flavor variations of the fruiting body have been overlooked. Here, we comprehensively investigated the volatile flavor profiles of different tissues, including the pileus skin, context, gill, and stipe of the fruiting body, of two widely cultivated L. edodes strains (T2 and 0912) using the gas chromatography-mass spectrometry (GC-MS) technique combined with a multivariate analysis. We show that the eight-carbon and sulfur compounds, which represented 43.2-78.0% and 1.4-42.9% of the total volatile emissions for strains 0912 and T2, respectively, dominated their volatile profiles. Compared with strain T2, strain 0912 had a higher total content of eight-carbon compounds but a lower total content of sulfur compounds in the fruiting body. The sulfur compounds represented 32.2% and 42.9% of the total volatile emissions for strains 0912 and T2, respectively. In contrast, they constituted only 1.4% in the stipes of strain 0912 and 9.0% in the skin of strain T2. The proportions of the predominant C8 compounds (1-octen-3-one, 1-octen-3-ol, and 3-octanone) and sulfur compounds (lenthionine, 1,2,4-trithiolane, dimethyl disulfide, and dimethyl trisulfide) changed depending on the tissues and strains. Using machine learning, we show that the prediction accuracy for different strains and tissues using their volatile profiles could reach 100% based on the highly diverse strain- and tissue-derived volatile variations. Our results reveal and highlight for the first time the comprehensive tissue-specific volatile flavor variations of the L. edodes fruiting body. These findings underscore the significance of considering strain and tissue differences as pivotal variables when aiming to develop products with volatile flavor characteristics.

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