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1.
Front Plant Sci ; 15: 1416221, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39253573

RESUMEN

The timely and accurate acquisition of crop-growth information is a prerequisite for implementing intelligent crop-growth management, and portable multispectral imaging devices offer reliable tools for monitoring field-scale crop growth. To meet the demand for obtaining crop spectra information over a wide band range and to achieve the real-time interpretation of multiple growth characteristics, we developed a novel portable snapshot multispectral imaging crop-growth sensor (PSMICGS) based on the spectral sensing of crop growth. A wide-band co-optical path imaging system utilizing mosaic filter spectroscopy combined with dichroic mirror beam separation is designed to acquire crop spectra information over a wide band range and enhance the device's portability and integration. Additionally, a sensor information and crop growth monitoring model, coupled with a processor system based on an embedded control module, is developed to enable the real-time interpretation of the aboveground biomass (AGB) and leaf area index (LAI) of rice and wheat. Field experiments showed that the prediction models for rice AGB and LAI, constructed using the PSMICGS, had determination coefficients (R²) of 0.7 and root mean square error (RMSE) values of 1.611 t/ha and 1.051, respectively. For wheat, the AGB and LAI prediction models had R² values of 0.72 and 0.76, respectively, and RMSE values of 1.711 t/ha and 0.773, respectively. In summary, this research provides a foundational tool for monitoring field-scale crop growth, which is important for promoting high-quality and high-yield crops.

2.
World J Gastrointest Surg ; 16(8): 2409-2425, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39220056

RESUMEN

Liver cancer represents a grave hepatic condition and constitutes a significant global health concern. Surgical resection remains the principal therapeutic modality for liver cancer. Nevertheless, perioperative malnutrition exerts a notable impact on patients with liver cancer, emerging as an independent risk factor for disease mortality and adverse outcomes. Hence, precise nutritional diagnosis and timely nutritional support hold the potential to enhance therapeutic efficacy and quality of life for liver cancer patients. This study represents a meticulous foray into the literature, extracting data from PubMed, Web of Science, and EMBASE databases, with a focus on the past 5 years. It scrutinizes the impact of malnutrition on patients undergoing liver cancer surgery, the etiological underpinnings of malnutrition within this patient cohort, the critical assessment of perioperative nutritional status, and the strategic approaches to nutritional support. Utilizing rigorous inclusion and exclusion criteria, the amassed scholarly works are meticulously synthesized, methodically organized, and categorically elaborated upon. Ultimately, the authors propose the incorporation of a multidisciplinary nutrition management team during the perioperative period, comprising nutritionists, pharmacists, physicians, nurses, psychologists, and rehabilitation therapists, among other specialized professionals. Together, they collaborate to devise and implement personalized nutritional support plans, monitor patients' nutritional status, and make necessary adjustments as required. Through comprehensive management and intervention, improvements in the nutritional status of liver cancer patients can be achieved, thereby enhancing surgical success rates and facilitating postoperative recovery. It is believed that this manuscript will offer valuable insights to advance the nutritional management during the perioperative phase of liver cancer, aiding in ameliorating patients' nutritional status and treatment outcomes.

3.
Plant Phenomics ; 6: 0200, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38978968

RESUMEN

Efficient and accurate acquisition of the rice grain protein content (GPC) is important for selecting high-quality rice varieties, and remote sensing technology is an attractive potential method for this task. However, the majority of multispectral sensors are poor predictors of GPC due to their broad spectral bands. Hyperspectral technology provides a new analytical technology for bridging the gap between phenomics and genomics. However, the small size of typical datasets is a constraint for model construction for estimating GPC, limiting their accuracy and reducing their ability to generalize to a wide range of varieties. In this study, we used hyperspectral data of rice grains from 515 japonica varieties and deep convolution generative adversarial networks (DCGANs) to generate simulated data to improve the model accuracy. Features sensitive to GPC were extracted after applying a continuous wavelet transform (CWT), and the estimated GPC model was constructed by partial least squares regression (PLSR). Finally, a genome-wide association study (GWAS) was applied to the measured and generated datasets to detect GPC loci. The results demonstrated that the simulated GPC values generated after 8,000 epochs were closest to the measured values. The wavelet feature (WF1743, 2), obtained from the data with the addition of 200 simulated samples, exhibited the highest GPC estimation accuracy (R 2 = 0.58 and RRMSE = 6.70%). The GWAS analysis showed that the estimated values based on the simulated data detected the same loci as the measured values, including the OsmtSSB1L gene related to grain storage protein. This study provides a new technique for the efficient genetic study of phenotypic traits in rice based on hyperspectral technology.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38695237

RESUMEN

AIMS: This study aimed to explore the change trend and group heterogeneity of psychosocial adjustment level and to determine its influencing factors among young and middle-aged patients with first-episode acute myocardial infarction (AMI). METHODS AND RESULTS: The Psychosocial Adjustment Scale of Illness was used to assess the psychosocial adjustment level of the patients at 1, 3, and 6 months after discharge, respectively. Data were analyzed using Pearson correlation analysis, generalized estimating equations, and growth mixed models. A total of 233 patients were included, and their psychosocial adjustment scores at the three-time points were 57.18 ± 15.50, 36.17 ± 15.02, and 24.22 ± 12.98, respectively. The trajectories of changes in patients' psychosocial adjustment levels were divided into three latent categories: moderate adjustment improvement group (72.5%), low adjustment improvement group (16.3%), and persistent maladjustment group (11.2%). Among them, predictors of the persistent maladjustment group included no spouse, low monthly family income per capita, normal body mass index, never smoking, never exercising, combined with hyperlipidemia, low social support, submission coping, and high perceived stress. CONCLUSIONS: The psychosocial adjustment level of young and middle-aged patients with first-episode AMI showed an upward trend within 6 months after discharge, and there was group heterogeneity in the change trajectory of psychosocial adjustment level. It is suggested that a multi-center, large-sample longitudinal study should be carried out in the future, and the time of follow-up investigation should be extended to further clarify the change trajectory and influencing factors of psychosocial adjustment of patients with different subtypes, to provide the theoretical basis for formulating targeted intervention programs.

5.
Sci Total Environ ; 940: 173531, 2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-38821277

RESUMEN

Extreme climate events such as frost and drought have great influence on wheat growth and yield. Understanding the effects of frost, drought and compound frost-dry events on wheat growth and yield is of great significance for ensuring national food security. In this study, wheat yield prediction model (SCYMvp) was developed by combining crop growth model (CGM), satellite images and meteorological variables. Wheat yield maps in the Huang-Huai-Hai Plain (HHHP) during 2001-2020 were generated using SCYMvp model. Meanwhile, accumulative frost days (AFD), accumulative dry days (ADD) and accumulative frost-dry days (AFDD) in different growth periods of wheat were calculated, and the effects of frost and drought on wheat yield were quantified by the first difference method and linear mixed model. The results showed that wheat yield increased significantly, while the rising trend was obvious at more than half of the regions. Extreme climate events (ECEs) showed a relatively stable change trend, although the change trend was significant only in a few areas. Compared with frost and drought in the early growth period, ECEs in the middle growth period (spring ECEs) had more negative effects on wheat growth and yield. Wheat yield was negatively correlated with spring ECEs, and yield loss was between 4.6 and 49.8 kg/ha for each 1 d increase of spring ECEs. The effects of spring ECEs on wheat yield were ranked as AFDD > AFD > ADD. The negative effect of ADD on wheat yield in the late growth period was higher than that in the other periods. The negative effects of spring ECEs on yield in southern regions were higher than those in northern regions. Overall, due to the adverse effects of frost and drought on wheat yield in the middle and late growth periods, the mean annual yield loss was 6.4 %, among which spring AFD caused the greatest loss to wheat yield (3.1 %). The results have important guiding significance for formulating climate adaptation management strategies.


Asunto(s)
Cambio Climático , Sequías , Estaciones del Año , Triticum , Triticum/crecimiento & desarrollo , China , Congelación , Análisis Espacio-Temporal
6.
J Ethnobiol Ethnomed ; 20(1): 55, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38790060

RESUMEN

BACKGROUND: The Daur people are one of the 55 minority ethnic groups in China and have lived in Northern China for 300 years. In traditional Daur medicine, medicinal and edible plants (MEPs) are utilised for health benefits and therapeutic purposes; however, related ethnobotanical knowledge is rarely reported, which is disadvantageous for the sustainable development of these MEPs. METHODS: Semi-structured interviews with 122 informants, six focus group discussions, and a resource survey were conducted in a Daur minority nationality area in Inner Mongolia from 2015 to 2020, and the data statistics were analysed. In this study, we simulated a system dynamics model aimed at understanding the multiple feedback mechanisms involved in the relationships between the cultural influences and socioeconomic factors, sustainable environment, and development of MEPs. RESULTS: A total of 52 species of MEPs were identified and relevant ethnobotanical knowledge was assessed using Daur medicinal species data from Inner Mongolia and the Xinjiang region, with the literature and Ewenki ethnic group data used for comparison. The most commonly used medicinal plant species by the Daur were found to be Betula pendula subsp. mandshurica, Artemisia integrifolia, Crataegus pinnatifida, Saposhnikovia divaricata, Artemisia argyi, and Jacobaea cannabifolia. The MEPs most frequently targeted the digestive and rheumatic immunity systems, as well as infectious diseases or parasitic infections and other common diseases and basic health issues. MEP knowledge was primarily limited to older generations; thus, the valuable ethnobotanical knowledge on traditional medicines must be protected from future losses. CONCLUSIONS: Our findings provide insights for future research aimed at exploiting the rich phytochemical diversity in traditional medicine and promote its use in modern lifestyles. Effective assessment and management of plant resources will lead to their application for the improvement of dietary diversity, nutrition, and health care.


Asunto(s)
Etnobotánica , Plantas Comestibles , Plantas Medicinales , Humanos , China , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Medicina Tradicional China , Etnicidad , Encuestas y Cuestionarios , Adulto Joven , Pueblos del Este de Asia
7.
J Clin Pharmacol ; 64(8): 1030-1043, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38654529

RESUMEN

Voriconazole is the first-line treatment for invasive aspergillosis. Its pharmacokinetics exhibit considerable inter- and intra-individual variability. The purpose of this study was to investigate the effects of CYP2C19, CYP2C9, CYP3A4, and FMO3 genetic polymorphisms and sex on the pharmacokinetics of voriconazole in healthy Chinese adults receiving single-dose and multiple-dose voriconazole, to provide a reference for its clinical individualized treatment. A total of 123 healthy adults were enrolled in the study, with 108 individuals and 15 individuals in the single-dose and multiple-dose doses, respectively. Plasma voriconazole concentrations were measured using a validated LC-MS/MS method, and pharmacokinetics parameters were calculated using the non-compartmental method with WinNonlin 8.2. CYP2C19, CYP2C9, CYP3A4, and FMO3 single-nucleotide polymorphisms were sequenced using the Illumina Hiseq X-Ten platform. The results suggested that CYP2C19 genetic polymorphisms significantly affected the pharmacokinetics of voriconazole at single doses of 4, 6, and 8 mg/kg and multiple doses of voriconazole. CYP3A4 rs2242480 had a significant effect on AUC0-∞ (area under the plasma concentration-time curve from time 0 to infinity) and MRT (mean residence time) of voriconazole at a single dose of 4 mg/kg in CYP2C19 extensive metabolizer. Regardless of the CYP2C19 genotype, CYP2C9 rs1057910 and FMO3 rs2266780 were not associated with the pharmacokinetics of voriconazole at three single-dose levels or multiple doses. No significant differences in most voriconazole pharmacokinetics parameters were noted between male and female participants after single and multiple dosing. For patients receiving voriconazole treatment, CYP2C19 genetic polymorphisms should be genotyped for its precision administration. In contrast, based on our study of healthy Chinese adults, it seems unnecessary to consider the effects of CYP2C9, CYP3A4, and FMO3 genetic polymorphisms on voriconazole pharmacokinetics.


Asunto(s)
Antifúngicos , Pueblo Asiatico , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2C9 , Citocromo P-450 CYP3A , Oxigenasas , Polimorfismo de Nucleótido Simple , Voriconazol , Humanos , Voriconazol/farmacocinética , Voriconazol/sangre , Voriconazol/administración & dosificación , Masculino , Femenino , Citocromo P-450 CYP2C19/genética , Oxigenasas/genética , Adulto , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Antifúngicos/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/sangre , Adulto Joven , Pueblo Asiatico/genética , Factores Sexuales , Voluntarios Sanos , Genotipo , Pueblos del Este de Asia
8.
Eur J Med Chem ; 268: 116232, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38377825

RESUMEN

Coronavirus entry into host cells hinges on the interaction between the spike glycoprotein of the virus and the cell-surface receptor angiotensin-converting enzyme 2 (ACE2), initiating the subsequent clathrin-mediated endocytosis (CME) pathway. AP-2-associated protein kinase 1 (AAK1) holds a pivotal role in this pathway, regulating CME by modulating the phosphorylation of the µ subunit of adaptor protein 2 (AP2M1). Herein, we report a series of novel AAK1 inhibitors based on previously reported 1,2,4a,5-tetrahydro-4H-benzo[b] [1,4]oxazino[4,3-d] [1,4]oxazine scaffold. Among 23 synthesized compounds, compound 12e is the most potent one with an IC50 value of 9.38 ± 0.34 nM against AAK1. The in vitro antiviral activity of 12e against SARS-CoV-2 was evaluated using a model involving SARS-CoV-2 pseudovirus infecting hACE2-HEK293 host cells. The results revealed that 12e was superior in vitro antiviral activity against SARS-CoV-2 entry into host cells when compared to SGC-AAK1-1 and LX9211, and its activity was comparable to that of a related and reference compound 8. Mechanistically, all AAK1 inhibitors attenuated AAK1-induced phosphorylation of AP2M1 threonine 156 and disrupted the direct interaction between AP2M1 and ACE2, ultimately inhibiting SARS-CoV-2 infection. Notably, compounds 8 and 12e exhibited a more potent effect in suppressing the phosphorylation of AP2M1 T156 and the interaction between AP2M1 and ACE2. In conclusion, novel AAK1 inhibitor 12e demonstrates significant efficacy in suppressing SARS-CoV-2 infection, and holds promise as a potential candidate for developing novel antiviral drugs against SARS-CoV-2 and other coronavirus infections.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Inhibidores de Proteínas Quinasas/farmacología , Enzima Convertidora de Angiotensina 2 , Células HEK293 , Unión Proteica , Antivirales/farmacología , Internalización del Virus , Proteínas Serina-Treonina Quinasas/metabolismo
9.
Molecules ; 29(3)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38338343

RESUMEN

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs.


Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Humanos , Lactante , Anciano , Antivirales/farmacología , Antivirales/uso terapéutico , Palivizumab/farmacología , Palivizumab/uso terapéutico , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/prevención & control , Antirretrovirales/uso terapéutico
10.
Adv Biol (Weinh) ; 8(5): e2300117, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38379270

RESUMEN

The incidence of Hepatocellular carcinoma (HCC) and HCC-related deaths have remarkably increased over the recent decades. It has been reported that ß-catenin activation can be frequently observed in HCC cases. This study identified the integrin-linked kinase-associated phosphatase (ILKAP) as a novel ß-catenin-interacting protein. ILKAP is localized both in the nucleus and cytoplasm and regulates the WNT pathway in different ways. First, it is demonstrated that ILKAP activates the WNT pathway in HCC cells by increasing the protein level of ß-catenin and other proteins associated with the WNT signaling, such as c-Myc and CyclinD1. Next, it is shown that ILKAP promotes the metastasis of HCC both in vitro and in vivo in a zebrafish xenograft model. It is also found that ILKAP dephosphorylates the GSK3ß and CK1, contributing to the reduced ubiquitination of ß-catenin. Furthermore, it is identified that ILKAP functions by mediating binding between TCF4 and ß-catenin to enhance expression of WNT target genes. Taken together, the study demonstrates a critical function of ILKAP in metastasis of HCC, since ILKAP is crucial for the activation of the WNT pathway via stabilization of ß-catenin and increased binding between TCF4 and ß-catenin.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Fosfoproteínas Fosfatasas , Vía de Señalización Wnt , beta Catenina , Animales , Humanos , beta Catenina/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Metástasis de la Neoplasia , Factor de Transcripción 4/metabolismo , Factor de Transcripción 4/genética , Vía de Señalización Wnt/fisiología , Pez Cebra , Fosfoproteínas Fosfatasas/genética , Fosfoproteínas Fosfatasas/metabolismo
11.
Toxics ; 12(2)2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38393251

RESUMEN

This study presents an electrolysis system utilizing a novel self-circulation process of sulfate (SO42-) and persulfate (S2O82-) ions based on a boron-doped diamond (BDD) anode and an activated carbon fiber (ACF) cathode, which is designed to enable electrochemical remediation of environmental contaminants with reduced use of chemical reagents and minimized residues. The production of S2O82- and hydrogen peroxide (H2O2) on the BDD anode and ACF cathode, respectively, is identified as the source of active radicals for the contaminant degradation. The initiator, sulfate, is identified by comparing the degradation efficiency in NaSO4 and NaNO3 electrolytes. Quenching experiments and electron paramagnetic resonance (EPR) spectroscopy confirmed that the SO4-· and ·OH generated on the ACF cathode are the main reactive radicals. A comparison of the degradation efficiency and the generated S2O82-/H2O2 of the divided/undivided electrolysis system is used to demonstrate the superiority of the synergistic effect between the BDD anode and ACF cathode. This work provides evidence of the effectiveness of the philosophy of "catalysis in lieu of supplementary chemical agents" and sheds light on the mechanism of the generation and transmission of reactive species in the BDD and ACF electrolysis system, thereby offering new perspectives for the design and optimization of electrolysis systems.

12.
Plant Methods ; 20(1): 15, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38287423

RESUMEN

The number of seedlings is an important indicator that reflects the size of the wheat population during the seedling stage. Researchers increasingly use deep learning to detect and count wheat seedlings from unmanned aerial vehicle (UAV) images. However, due to the small size and diverse postures of wheat seedlings, it can be challenging to estimate their numbers accurately during the seedling stage. In most related works in wheat seedling detection, they label the whole plant, often resulting in a higher proportion of soil background within the annotated bounding boxes. This imbalance between wheat seedlings and soil background in the annotated bounding boxes decreases the detection performance. This study proposes a wheat seedling detection method based on a local annotation instead of a global annotation. Moreover, the detection model is also improved by replacing convolutional and pooling layers with the Space-to-depth Conv module and adding a micro-scale detection layer in the YOLOv5 head network to better extract small-scale features in these small annotation boxes. The optimization of the detection model can reduce the number of error detections caused by leaf occlusion between wheat seedlings and the small size of wheat seedlings. The results show that the proposed method achieves a detection accuracy of 90.1%, outperforming other state-of-the-art detection methods. The proposed method provides a reference for future wheat seedling detection and yield prediction.

13.
Eur J Cardiovasc Nurs ; 23(3): 267-277, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37503729

RESUMEN

AIMS: We sought to explore the latent classifications of psychosocial adaptation in young and middle-aged patients with acute myocardial infarction (AMI) and analyse the characteristics of different profiles of AMI patients. METHODS AND RESULTS: A cross-sectional study was performed in 438 Chinese young and middle-aged patients with AMI. The investigation time was 1 month after discharge. Three different self-report instruments were distributed to the participants, including the Psychosocial Adjustment to Illness Scale, the Perceived Stress Scale, and the Social Support Rating Scale. The seven dimensions of the Psychosocial Adjustment to Illness Scale were then used to perform a latent profile analysis. All participants signed informed consent forms in accordance with the ethical principles of the Declaration of Helsinki. Finally, a total of 411 young and middle-aged AMI patients were enrolled. Three distinct profiles were identified, including the 'well-adapted group' (44.8%), 'highlight in psychological burdens group' (25.5%), and 'poorly adapted group' (29.7%). The influencing factors included stress perception, social support, occupational type, and marital status (P < 0.05). CONCLUSION: The psychosocial adaptation of young and middle-aged AMI patients can be divided into three profiles. Clinical nurses can carry out individualized psychological interventions according to the characteristics of patients in different potential profiles to improve the psychosocial adaptation of patients and the prognosis of their disease.


Asunto(s)
Infarto del Miocardio , Pruebas Psicológicas , Persona de Mediana Edad , Humanos , Estudios Transversales , Autoinforme , Infarto del Miocardio/psicología , Pronóstico
14.
Chem Biol Interact ; 387: 110811, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-37993078

RESUMEN

Ciprofol is a novel intravenous anesthetic agent. Its major glucuronide metabolite, M4, is found in plasma and urine. However, the specific isoforms of UDP-glucuronosyltransferases (UGTs) that metabolize ciprofol to M4 remain unknown. This study systematically characterized UGTs that contribute to the formation of M4 using human liver microsomes (HLM), human intestinal microsomes (HIM), and human recombinant UGTs. The inhibitory potential of ciprofol and M4 against major human UGTs and cytochrome P450 enzymes (P450s) was also explored. In vitro-in vivo extrapolation (IVIVE) and physiologically-based pharmacokinetic (PBPK) simulations were performed to predict potential in vivo drug-drug interactions (DDIs) caused by ciprofol. Glucuronidation of ciprofol followed Michaelis-Menten kinetics in both HLM and HIM with apparent Km values of 345 and 412 µM, Vmax values of 2214 and 444 nmol min-1·mg protein-1, respectively. The in vitro intrinsic clearances (CLint = Vmax/Km) for ciprofol glucuronidation by HLM and HIM were 6.4 and 1.1 µL min-1·mg protein-1, respectively. Human recombinant UGT studies revealed that UGT1A9 is the predominant isoform mediating M4 formation, followed by UGT1A7, with UGT1A8 playing a minor role. Ciprofol competitively inhibited CYP1A2 (Ki = 12 µM) and CYP2B6 (Ki = 4.7 µM), and noncompetitively inhibited CYP2C19 (Ki = 29 µM). No time-dependent inhibition by ciprofol was noted for CYP1A2, CYP2B6, or CYP2C19. In contrast, M4 showed limited or no inhibitory effects against selected P450s. Neither ciprofol nor M4 inhibited UGTs significantly. Initial IVIVE suggested potential ciprofol-mediated inhibition of CYP1A2, CYP2B6, and CYP2C19 inhibition in vivo. However, PBPK simulations showed no significant effect on phenacetin, bupropion, and S-mephenytoin exposure or peak plasma concentration. Our findings are pertinent for future DDI studies of ciprofol as either a perpetrator or victim drug.


Asunto(s)
Citocromo P-450 CYP1A2 , Microsomas Hepáticos , Humanos , Citocromo P-450 CYP2B6/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP2C19/metabolismo , Microsomas Hepáticos/metabolismo , Glucuronosiltransferasa/metabolismo , Interacciones Farmacológicas , Cinética
15.
Can J Microbiol ; 70(3): 102-108, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38096506

RESUMEN

Arsenic (As) is a metal with potentially toxic effects on different organisms. Hydrogen sulfide (H2S) plays a vital role in mitigating heavy metal toxicity by reducing oxidative stress in plants and animals. However, the role of H2S in alleviating arsenic toxicity in yeast cells remains unclear. In this study, the role of NaHS (exogenous physiological H2S) in alleviating As-induced yeast cell death was investigated. Yeast cells in the logarithmic phase were pretreated with 0.05 mmol/L NaHS for 6 h, and then incubated in the YPD medium with or without 1 mmol/L As. After 12 h of treatment, relative survival rate, H2S content, oxidative stress biomarkers, and antioxidant machinery were measured. Our results showed that sodium arsenite-induced yeast cell death and pretreatment with 0.05 mmol/L NaHS significantly alleviated sodium arsenite-induced cell death. Under sodium arsenite conditions, the levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) increased, accompanied by the inhibition of the catalase (CAT) activity and the downregulation of CTT1 expression. However, the activities of the superoxide dismutase (SOD) and glutathion peroxidase (GPX) increased, and the expression of SOD1 and GPX2 was markedly upregulated in the group treated with sodium arsenite. When yeast cells were pretreated with NaHS, the intracellular ROS and MDA levels decreased significantly, and the activities of SOD, CAT, and GPX increased significantly. This was associated with a significant increase in relative survival rate and H2S content compared to the arsenic treatment alone. Our findings indicate that NaHS alleviates sodium arsenite-induced yeast cell death, mainly by enhancing the antioxidant defense system.


Asunto(s)
Arsénico , Arsenitos , Sulfuro de Hidrógeno , Compuestos de Sodio , Sulfuros , Animales , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Saccharomyces cerevisiae/metabolismo , Arsénico/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Muerte Celular
16.
Channels (Austin) ; 18(1): 2290807, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38062897

RESUMEN

Voltage-gated calcium (Cav) channels mediate Ca2+ influx in response to membrane depolarization, playing critical roles in diverse physiological processes. Dysfunction or aberrant regulation of Cav channels can lead to life-threatening consequences. Cav-targeting drugs have been clinically used to treat cardiovascular and neuronal disorders for several decades. This review aims to provide an account of recent developments in the structural dissection of Cav channels. High-resolution structures have significantly advanced our understanding of the working and disease mechanisms of Cav channels, shed light on the molecular basis for their modulation, and elucidated the modes of actions (MOAs) of representative drugs and toxins. The progress in structural studies of Cav channels lays the foundation for future drug discovery efforts targeting Cav channelopathies.


Asunto(s)
Canales de Calcio , Canalopatías , Humanos , Canales de Calcio/metabolismo , Señalización del Calcio , Calcio/metabolismo , Biología
17.
Plant Phenomics ; 5: 0109, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37915995

RESUMEN

Accurate wheat spike detection is crucial in wheat field phenotyping for precision farming. Advances in artificial intelligence have enabled deep learning models to improve the accuracy of detecting wheat spikes. However, wheat growth is a dynamic process characterized by important changes in the color feature of wheat spikes and the background. Existing models for wheat spike detection are typically designed for a specific growth stage. Their adaptability to other growth stages or field scenes is limited. Such models cannot detect wheat spikes accurately caused by the difference in color, size, and morphological features between growth stages. This paper proposes WheatNet to detect small and oriented wheat spikes from the filling to the maturity stage. WheatNet constructs a Transform Network to reduce the effect of differences in the color features of spikes at the filling and maturity stages on detection accuracy. Moreover, a Detection Network is designed to improve wheat spike detection capability. A Circle Smooth Label is proposed to classify wheat spike angles in drone imagery. A new micro-scale detection layer is added to the network to extract the features of small spikes. Localization loss is improved by Complete Intersection over Union to reduce the impact of the background. The results show that WheatNet can achieve greater accuracy than classical detection methods. The detection accuracy with average precision of spike detection at the filling stage is 90.1%, while it is 88.6% at the maturity stage. It suggests that WheatNet is a promising tool for detection of wheat spikes.

18.
Cell ; 186(24): 5363-5374.e16, 2023 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-37972591

RESUMEN

Cav1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Cav1.2, both in its apo form and in complex with several drugs, as well as the peptide neurotoxin calciseptine. Most structures, apo or bound to calciseptine, amlodipine, or a combination of amiodarone and sofosbuvir, exhibit a consistent inactivated conformation with a sealed gate, three up voltage-sensing domains (VSDs), and a down VSDII. Calciseptine sits on the shoulder of the pore domain, away from the permeation path. In contrast, when pinaverium bromide, an antispasmodic drug, is inserted into a cavity reminiscent of the IFM-binding site in Nav channels, a series of structural changes occur, including upward movement of VSDII coupled with dilation of the selectivity filter and its surrounding segments in repeat III. Meanwhile, S4-5III merges with S5III to become a single helix, resulting in a widened but still non-conductive intracellular gate.


Asunto(s)
Canales de Calcio Tipo L , Venenos Elapídicos , Humanos , Canales de Calcio Tipo L/química , Canales de Calcio Tipo L/metabolismo , Neurotoxinas , Dominios Proteicos , Microscopía por Crioelectrón
19.
Plant Methods ; 19(1): 134, 2023 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-38007501

RESUMEN

BACKGROUND: The metrics for assessing the yield of crops in the field include the number of ears per unit area, the grain number per ear, and the thousand-grain weight. Typically, the ear number per unit area contributes the most to the yield. However, calculation of the ear number tends to rely on traditional manual counting, which is inefficient, labour intensive, inaccurate, and lacking in objectivity. In this study, two novel extraction algorithms for the estimation of the wheat ear number were developed based on the use of terrestrial laser scanning (TLS) in conjunction with the density-based spatial clustering (DBSC) algorithm based on the normal and the voxel-based regional growth (VBRG) algorithm. The DBSC involves two steps: (1) segmentation of the point clouds using differences in the normal vectors and (2) clustering of the segmented point clouds using a density clustering algorithm to calculate the ear number. The VBRG involves three steps: (1) voxelization of the point clouds, (2) construction of the topological relationships between the voxels as a connected region using the k-dimensional tree, and (3) detection of the wheat ears in the connected areas using a regional growth algorithm. RESULTS: The results demonstrated that DBSC and VBRG were promising in estimating the number of ears for different cultivars, planting densities, N fertilization rates, and growth stages of wheat (RMSE = 76 ~ 114 ears/m2, rRMSE = 18.62 ~ 27.96%, r = 0.76 ~ 0.84). Comparing the performance of the two algorithms, the overall accuracy of the DBSC (RMSE = 76 ears/m2, rRMSE = 18.62%, r = 0.84) was better than that of the VBRG (RMSE = 114 ears/m2, rRMSE = 27.96%, r = 0.76). It was found that with the DBSC, the calculation in points as units permitted more detailed information to be retained, and this method was more suitable for estimation of the wheat ear number in the field. CONCLUSIONS: The algorithms adopted in this study provide new approaches for non-destructive measurement and efficient acquisition of the ear number in the assessment of the wheat yield phenotype.

20.
J Org Chem ; 88(19): 14193-14199, 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37696811

RESUMEN

A [4 + 1] cyclization and C-C bond cleavage process mediated reaction for constructing 3-carbonyl imidazo[1,5-a] pyridines from 1,3-dicarbonyl compounds and pyridin-2-ylmethanamines has been developed. Various 1,3-dicarbonyl compounds are applicable, and selectivity could be achieved. Importantly, this strategy could be extended to an atom economy method by employing a cyclic 1,3-dicarbonyl compound, and it provided a new view for C-C bond cleavage reactions.

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