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1.
BMC Plant Biol ; 24(1): 166, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38433195

RESUMEN

BACKGROUND: Chlorophyll (Chl) is an agronomic trait associated with photosynthesis and yield. Gibberellin 2-oxidases (GA2oxs) have previously been shown to be involved in Chl accumulation. However, whether and how the PbrGA2ox proteins (PbrGA2oxs) mediate Chl accumulation in pear (Pyrus spp.) is scarce. RESULTS: Here, we aimed to elucidate the role of the pear GA2ox gene family in Chl accumulation and the related underlying mechanisms. We isolated 13 PbrGA2ox genes (PbrGA2oxs) from the pear database and identified PbrGA2ox1 as a potential regulator of Chl accumulation. We found that transiently overexpressing PbrGA2ox1 in chlorotic pear leaves led to Chl accumulation, and PbrGA2ox1 silencing in normal pear leaves led to Chl degradation, as evident by the regreening and chlorosis phenomenon, respectively. Meanwhile, PbrGA2ox1-overexpressing (OE) tobacco plants discernably exhibited Chl built-up, as evidenced by significantly higher Pn and Fv/Fm. In addition, RNA sequencing (RNA-seq), physiological and biochemical investigations revealed an increase in abscisic acid (ABA), methyl jasmonate (MeJA), and salicylic acid (SA) concentrations and signaling pathways; a marked elevation in reducing and soluble sugar contents; and a marginal decline in the starch and sucrose levels in OE plants. Interestingly, PbrGA2ox1 overexpression did not prominently affect Chl synthesis. However, it indeed facilitated chloroplast development by increasing chloroplast number per cell and compacting the thylakoid granum stacks. These findings might jointly contribute to Chl accumulation in OE plants. CONCLUSION: Overall, our results suggested that GA2oxs accelerate Chl accumulation by stimulating chloroplast development and proved the potential of PbrGA2ox1 as a candidate gene for genetically breeding biofortified pear plants with a higher yield.


Asunto(s)
Clorofila , Pyrus , Pyrus/genética , Fitomejoramiento , Cloroplastos/genética , Tilacoides
2.
BMC Plant Biol ; 24(1): 619, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38937683

RESUMEN

BACKGROUND: Anthracnose, mainly caused by Colletotrichum fructicola, leads to severe losses in pear production. However, there is limited information available regarding the molecular response to anthracnose in pears. RESULTS: In this study, the anthracnose-resistant variety 'Seli' and susceptible pear cultivar 'Cuiguan' were subjected to transcriptome analysis following C. fructicola inoculation at 6 and 24 h using RNA sequencing. A total of 3186 differentially expressed genes were detected in 'Seli' and 'Cuiguan' using Illumina sequencing technology. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that the transcriptional response of pears to C. fructicola infection included responses to reactive oxygen species, phytohormone signaling, phenylpropanoid biosynthesis, and secondary metabolite biosynthetic processes. Moreover, the mitogen-activated protein kinase (MAPK) signaling pathway and phenylpropanoid biosynthesis were involved in the defense of 'Seli'. Furthermore, the gene coexpression network data showed that genes related to plant-pathogen interactions were associated with C. fructicola resistance in 'Seli' at the early stage. CONCLUSION: Our results showed that the activation of specific genes in MAPK, calcium signaling pathways and phenylpropanoid biosynthesis was highly related to C. fructicola resistance in 'Seli' and providing several potential candidate genes for breeding anthracnose-resistant pear varieties.


Asunto(s)
Colletotrichum , Resistencia a la Enfermedad , Perfilación de la Expresión Génica , Enfermedades de las Plantas , Pyrus , Pyrus/microbiología , Pyrus/genética , Colletotrichum/fisiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , Transcriptoma , Regulación de la Expresión Génica de las Plantas
3.
New Phytol ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39044442

RESUMEN

Plants delicately regulate endogenous auxin levels through the coordination of transport, biosynthesis, and inactivation, which is crucial for growth and development. While it is well-established that the actin cytoskeleton can regulate auxin levels by affecting polar transport, its potential role in auxin biosynthesis has remained largely unexplored. Using LC-MS/MS-based methods combined with fluorescent auxin marker detection, we observed a significant increase in root auxin levels upon deletion of the actin bundling proteins AtFIM4 and AtFIM5. Fluorescent observation, immunoblotting analysis, and biochemical approaches revealed that AtFIM4 and AtFIM5 affect the protein abundance of the key auxin synthesis enzyme YUC8 in roots. AtFIM4 and AtFIM5 regulate the auxin synthesis enzyme YUC8 at the protein level, with its degradation mediated by the 26S proteasome. This regulation modulates auxin synthesis and endogenous auxin levels in roots, consequently impacting root development. Based on these findings, we propose a molecular pathway centered on the 'actin cytoskeleton-26S proteasome-YUC8-auxin' axis that controls auxin levels. Our findings shed light on a new pathway through which plants regulate auxin synthesis. Moreover, this study illuminates a newfound role of the actin cytoskeleton in regulating plant growth and development, particularly through its involvement in maintaining protein homeostasis via the 26S proteasome.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38926162

RESUMEN

PURPOSE: Claudin18.2 (CLDN18.2) is a novel target for diagnosis and therapy of gastrointestinal cancer. This study aimed to evaluate the safety and feasibility of a novel CLDN18.2-targeted nanobody, PMD22, labeled with gallium-68 ([68Ga]Ga), for detecting CLDN18.2 expression in patients with gastrointestinal cancer using PET/CT imaging. METHODS: [68Ga]Ga-PMD22 was synthesized based on the nanobody, and its cell binding properties were assayed. Preclinical pharmacokinetics were determined in CLDN18.2-positive xenografts using microPET/CT. Effective dosimetry of [68Ga]Ga-PMD22 was evaluated in 5 gastrointestinal cancer patients, and PET/CT imaging of [68Ga]Ga-PMD22 and [18F]FDG were performed head-to-head in 16 gastrointestinal cancer patients. Pathological tissues were obtained for CLDN18.2 immunohistochemical (IHC) staining and comparative analysis with PET/CT findings. RESULTS: Cell binding assay showed that [68Ga]Ga-PMD22 had a higher binding ability to AGSCLDN18.2 and BGC823CLDN18.2 cells than to AGS and BGC823 cells (p < 0.001). MicroPET/CT images showed that [68Ga]Ga-PMD22 rapidly accumulated in AGSCLDN18.2 and BGC823CLDN18.2 tumors, and high contrast tumor to background imaging was clearly observed. In the pilot study, the effective dose of [68Ga]Ga-PMD22 was 1.68E-02 ± 1.45E-02 mSv/MBq, and the CLDN18.2 IHC staining result was highly correlated with the SUVmax/BKGstomach of [68Ga]Ga-PMD22 (rs = 0.848, p < 0.01). CONCLUSION: A novel [68Ga]Ga-labeled nanobody probe targeting CLDN18.2, [68Ga]Ga-PMD22, was established and preliminarily proved to be safe and effective in revealing CLDN18.2-positive gastrointestinal cancer, providing a basis for the clinical translation of the agent. CLINICAL TRIAL REGISTRATION: This study was registered on the ClinicalTrials.gov (NCT05937919).

5.
Theor Appl Genet ; 137(1): 23, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38231256

RESUMEN

KEY MESSAGE: Integrated QTL mapping and WGCNA condense the potential gene regulatory network involved in oil accumulation. A glycosyl hydrolases gene (GhHSD1) for oil biosynthesis was confirmed in Arabidopsis, which will provide useful knowledge to understand the functional mechanism of oil biosynthesis in cotton. Cotton is an economical source of edible oil for the food industry. The genetic mechanism that regulates oil biosynthesis in cottonseeds is essential for the genetic enhancement of oil content (OC). To explore the functional genomics of OC, this study utilized an interspecific backcross inbred line population to dissect the quantitative trait locus (QTL) interlinked with OC. In total, nine OC QTLs were identified, four of which were novel, and each QTL explained 3.62-34.73% of the phenotypic variation of OC. The comprehensive transcript profiling of developing cottonseeds revealed 3,646 core genes differentially expressed in both inbred parents. Functional enrichment analysis determined 43 genes were annotated with oil biosynthesis processes. Implementation of weighted gene co-expression network analysis showed that 803 differential genes had a significant correlation with the OC phenotype. Further integrated analysis identified seven important genes located in OC QTLs. Of which, the GhHSD1 gene located in stable QTL qOC-Dt3-1 exhibited the highest functional linkages with the other network genes. Phylogenetic analysis showed significant evolutionary differences in the HSD1 sequences between oilseed- and starch- crops. Furthermore, the overexpression of GhHSD1 in Arabidopsis yielded almost 6.78% higher seed oil. This study not only uncovers important genetic loci for oil accumulation in cottonseed, but also provides a set of new candidate genes that potentially influence the oil biosynthesis pathway in cottonseed.


Asunto(s)
Arabidopsis , Gossypium , Gossypium/genética , Aceite de Semillas de Algodón , Filogenia , Genómica
6.
Mol Pharm ; 21(2): 735-744, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38193393

RESUMEN

Fibroblast activation protein (FAP) is an emerging target for cancer diagnosis. Different types of FAP inhibitor (FAPI)-based radiotracers have been developed and applied for tumor imaging. However, few FAPI tracers for single photon emission computed tomography (SPECT) imaging have been reported. SPECT imaging is less expensive and more widely distributed than positron emission tomography (PET), and thus, 99mTc-labeled FAPIs would be more available to patients in developing regions. Herein, we developed a FAPI-04-derived radiotracer, HYNIC-FAPi-04 (HFAPi), for SPECT imaging. 99mTc-HFAPi, with a radiochemical purity of >98%, was prepared using a kit formula within 30 min. The specificity of 99mTc-HFAPi for FAP was validated by a cell binding assay in vitro and SPECT/CT imaging in vivo. The binding affinity (Kd value) of 99mTc-HFAPi for human FAP and murine FAP was 4.49 and 2.07 nmol/L, respectively. SPECT/CT imaging in HT1080-hFAP tumor-bearing mice showed the specific FAP targeting ability of 99mTc-HFAPi in vivo. In U87MG tumor-bearing mice, 99mTc-HFAPi had a higher tumor uptake compared with that of HT1080-hFAP and 4T1-mFAP tumor models. Interestingly, 99mTc-HFAPi showed a relatively high uptake in some murine joints. 99mTc-HFAPi accumulated in tumor lesions with a high tumor-to-background ratio. A preliminary clinical study was also performed in breast cancer patients. Additionally, 99mTc-HFAPi exhibited an advantage over 18F-FDG in the detection of lymph node metastatic lesions in breast cancer patients, which is helpful in improving treatment strategies. In short, 99mTc-HFAPi showed excellent affinity and specificity for FAP and is a promising SPECT radiotracer for (re)staging and treatment planning of breast cancers.


Asunto(s)
Neoplasias de la Mama , Tomografía Computarizada de Emisión de Fotón Único , Humanos , Animales , Ratones , Femenino , Línea Celular Tumoral , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tomografía de Emisión de Positrones , Fibroblastos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos
7.
Mol Pharm ; 21(4): 1977-1986, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38395797

RESUMEN

The expression level of PD-L1 in tumor tissue is considered one of the effective biomarkers to guide PD-1/PD-L1 therapy. Quantifying whole-body PD-L1 expression by SPECT imaging may help in selecting patients that potentially respond to PD-1/PD-L1 therapy. Nanobody is the smallest antibody fragment with antigen-binding ability that is well suited for radionuclide imaging. Nevertheless, high retention of radioactivity in the kidney may limit its clinical translation. The present study aimed to screen, design, and prepare a nanobody-based SPECT probe with rapid renal clearance to evaluate the PD-L1 expression level in vivo noninvasively. A phage library was constructed by immunizing alpaca with recombinant human PD-L1 protein, and 17 anti-PD-L1 nanobodies were screened by the phage display technique. After sequence alignment and flow cytometry analysis, APN09 was selected as the candidate nanobody, and a GGGC chelator was attached to its C-terminus for 99mTc labeling to prepare a SPECT imaging probe. The affinity and specificity of 99mTc-APN09 were evaluated by protein and cell-binding experiments, and SPECT imaging and biodistribution were performed in a mouse model with bilateral transplantation of A549 and A549PD-L1 tumors. The ability of 99mTc-APN09 to quantify the PD-L1 expression level in vivo was validated in tumor models with different PD-L1 expression levels. 99mTc-APN09 had a radiochemical purity higher than 99% and a binding equilibrium dissociation constant of 21.44 ± 1.65 nM with hPD-L1, showing high affinity. SPECT imaging results showed that 99mTc-APN09 could efficiently detect PD-L1-positive tumors within 0.5 h, and the quantitative results of SPECT were well correlated with the expression level of PD-L1 in cell lines. SPECT imaging and biodistribution results also showed that 99mTc-APN09 was rapidly cleared from the kidney in 2 h postinjection. 99mTc-APN09 was a simple and stable tool for visualizing PD-L1 expression in the whole body. In addition, due to its significant reduction in renal retention, it has better prospects for clinical translation.


Asunto(s)
Antígeno B7-H1 , Neoplasias , Animales , Humanos , Ratones , Antígeno B7-H1/metabolismo , Neoplasias/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón Único/métodos , Camélidos del Nuevo Mundo
8.
Physiol Plant ; 176(3): e14303, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38698659

RESUMEN

Cotton is an important cash crop for the textile industry. However, the understanding of natural genetic variation of fiber elongation in relation to miRNA is lacking. A miRNA gene (miR477b) was found to co-localize with a previously mapped fiber length (FL) quantitative trait locus (QTL). The miR477b was differentially expressed during fiber elongation between two backcross inbred lines (BILs) differing in FL and its precursor sequences. Bioinformatics and qRT-PCR analysis were further used to analyse the miRNA genes, which could produce mature miR477b. Cotton plants with virus-induced gene silencing (VIGS) constructs to over-express the allele of miR477b from the BIL with longer fibers had significantly longer fibers as compared with negative control plants, while the VIGS plants with suppressed miRNA expression had significantly shorter fibers. The expression level of the target gene (DELLA) and related genes (RDL1 and EXPA1 for DELLA through HOX3 protein) in the two BILs and/or the VIGS plants were generally congruent, as expected. This report represents one of the first comprehensive studies to integrate QTL linkage mapping and physical mapping of small RNAs with both small and mRNA transcriptome analysis, followed by VIGS, to identify candidate small RNA genes affecting the natural variation of fiber elongation in cotton.


Asunto(s)
Fibra de Algodón , Regulación de la Expresión Génica de las Plantas , Gossypium , MicroARNs , Sitios de Carácter Cuantitativo , Sitios de Carácter Cuantitativo/genética , Gossypium/genética , Gossypium/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Mapeo Cromosómico , Silenciador del Gen , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
9.
J Environ Manage ; 362: 121335, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38833934

RESUMEN

Transitional features of desert environments partially determine the risks associated with ecosystems. Influenced by climate change and human activities, the variability and uncertainty of desertification levels and ecological risks in the Qinghai Area of Qilian Mountain National Park (QMNPQA) has become increasingly prominent. As a critical ecological barrier in northwest China, monitoring desertification dynamics and ecological risks is crucial for maintaining ecosystem stability. This study identifies the optimal monitoring model from four constructed desertification monitoring models and analyzes spatiotemporal changes in desertification. The spatial and temporal changes in ecological risks and their primary driving factors were analyzed using methods such as raster overlay calculation, geographic detector, cloud model, and trend analysis. The main conclusions are as follows: The desertification feature spatial model based on GNDVI-Albedo demonstrates better applicability in the study area, with an inversion accuracy of 81.24%. The levels of desertification and ecological risks in QMNPQA exhibit significant spatial heterogeneity, with a gradual decrease observed from northwest to southeast. From 2000 to 2020, there is an overall decreasing trend in desertification levels and ecological risks, with the decreasing trend area accounting for 89.82% and 85.71% respectively, mainly concentrated in the southeastern and northwestern parts of the study area. The proportion of areas with increasing trends is 4.49% and 7.05% respectively, scattered in patches in the central and southern edge areas. Surface temperature (ST), Digital Elevation Map (DEM), and Green normalized difference vegetation index (GNDVI) are the most influential factors determining the spatial distribution of ecological risks in QMNPQA. The effects of management and climatic factors on ecological risks demonstrate a significant antagonistic effect, highlighting the positive contributions of human activities in mitigating the driving effects of climate change on ecological risks. The research results can provide reference for desertification prevention and ecological quality improvement in QMNPQA.


Asunto(s)
Cambio Climático , Conservación de los Recursos Naturales , Ecosistema , Actividades Humanas , Parques Recreativos , China , Humanos , Ecología
10.
J Environ Manage ; 358: 120817, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38593740

RESUMEN

Spartina alterniflora invasion is considered a critical event affecting sediment phosphorus (P) availability and stock. However, P retention and microbial phosphate solubilization in the sediments invaded with or without S. alterniflora have not been fully investigated. In this study, a sequential fractionation method and high-throughput sequencing were used to analyze P transformation and the underlying microbial mechanisms in the sediments of no plant (NP) zone, transition (T) zone, and plant (P) zone. Results showed that except for organic phosphate (OP), total phosphate (TP), inorganic phosphate (IP), and available phosphate (AP) all followed a significant decrease trend from the NP site to the T site, and to the P site. The vertical decrease of TP, IP, and AP was also observed with an increase in soil depth. Among the six IP fractions, Fe-P, Oc-P, and Ca10-P were the predominant forms, while the presence of S. alterniflora resulted in an obvious P depletion except for Ca8-P and Al-P. Although S. alterniflora invasion did not significantly alter the alpha diversity of phosphate-solubilizing bacteria (PSB) harboring phoD gene, several PSB belonging to p_Proteobacteria, p_Planctomycetes, and p_Cyanobacteriota showed close correlations with P speciation and IP fractions. Further correlation analysis revealed that the reduced soil pH, soil TN and soil EC, and the increased soil TOC mediated by the invasion of S. alterniflora also significantly correlated to these PSB. Overall, this study elucidates the linkage between PSB and P speciation and provides new insights into understanding P retention and microbial P transformation in the coastal sediment invaded by S. alterniflora.


Asunto(s)
Fosfatos , Fósforo , Poaceae , Humedales , China , Estuarios , Sedimentos Geológicos/microbiología
11.
Beilstein J Org Chem ; 20: 1914-1921, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39135661

RESUMEN

Isoquinolinone is an important heterocyclic framework in natural products and biologically active molecules, and the efficient synthesis of this structural motif has received much attention in recent years. Herein, we report a (phenyliodonio)sulfamate (PISA)-mediated, solvent-dependent synthesis of different isoquinolinone derivatives. The method provides highly chemoselective access to 3- or 4-substituted isoquinolinone derivatives by reacting o-alkenylbenzamide derivatives with PISA in either acetonitrile or wet hexafluoro-2-isopropanol.

13.
Heliyon ; 10(4): e26014, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38434050

RESUMEN

Neuroblastoma, predominantly afflicting young individuals, is characterized as an embryonal tumor, with poor prognosis primarily attributed to chemoresistance. This study delved into the impact of tripartite motif (TRIM) 59, an E3 ligase, on neuroblastoma development and chemosensitivity through mediating ferroptosis and the involvement of the tumor suppressor p53. Clinical samples were assessed for TRIM59 and p53 levels to explore their correlation with neuroblastoma differentiation. In neuroblastoma cells, modulation of TRIM59 expression, either through overexpression or knockdown, was coupled with doxorubicin hydrochloride (DOX) or ferrostatin-1 (Fer-1) therapy. In vivo assessments examined the influence of TRIM59 knockdown on neuroblastoma chemosensitivity to DOX. Co-immunoprecipitation and ubiquitination assays investigated the association between TRIM59 and p53. Proliferation was gauged with Cell Counting Kit-8, lipid reactive oxygen species (ROS) were assessed via flow cytometry, and protein levels were determined by Western blotting. TRIM59 expression was inversely correlated with neuroblastoma differentiation and positively linked to cell proliferation in response to DOX. Moreover, TRIM59 impeded lipid ROS generation and ferroptosis by directly interacting with p53, promoting its ubiquitination and degradation in DOX-exposed neuroblastoma cells. Fer-1 countered the impact of TRIM59 knockdown on neuroblastoma, while TRIM59 knockdown enhanced the therapeutic efficacy of DOX in xenograph mice. This study underscores TRIM59 as an oncogene in neuroblastoma, fostering growth and chemoresistance by suppressing ferroptosis through p53 ubiquitination and degradation. TRIM59 emerges as a potential strategy for neuroblastoma therapy.

14.
Heliyon ; 10(11): e32089, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38882368

RESUMEN

Introduction: Body mass index (BMI) can predict mortality in critically ill patients. Moreover, mortality is related to increased bilirubin levels. Thus, herein, we aimed to investigate the effect of bilirubin levels on the usefulness of BMI in predicting mortality in critically ill patients. Methods: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC IV) database. Patients were divided into two groups according to their total bilirubin levels within 24 h. Cox proportional hazard regression models were applied to obtain adjusted hazard ratios and 95 % confidence intervals for the correlation between BMI categories and hospital mortality. The dose-response relationship was flexibly modeled using a restricted cubic spline (RCS) with three knots. Results: Of the 14376 patients included, 3.4 % were underweight, 29.3 % were of normal body weight, 32.2 % were overweight, and 35.1 % were obese. For patients with total bilirubin levels <2 mg/dL, hospital mortality was significantly lower in patients with obesity than in normal body weight patients (p < 0.05). However, the opposite results were observed for patients with total bilirubin levels ≥2 mg/dL. The Cox proportional hazard regression models suggested that the risk of death was lower in patients with overweightness and obesity than in normal body weight patients when the total bilirubin levels were <2 mg/dL, but not in the other case (total bilirubin levels ≥2 mg/dL). RCS analyses showed that, for patients with total bilirubin levels <2 mg/dL, the risk of death gradually decreased with increasing BMI. Conversely, for patients with total bilirubin levels ≥2 mg/dL, this risk did not decrease with increasing BMI until reaching obesity, after which it increased rapidly. Conclusion: BMI predicted the risk of death differently in critically ill patients with different bilirubin levels.

15.
ACS Pharmacol Transl Sci ; 7(8): 2465-2475, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39144570

RESUMEN

Claudin18.2 (CLDN18.2) has emerged as a significant target in the treatment of advanced gastric cancer. The screening of patients positive for CLDN18.2 is crucial for the effective application of targeted therapies specific to CLND18.2. In this study, we developed a novel nanobody-based probe, [99mTc]Tc-PHG102, for use in nuclear medicine. We analyzed its radiochemical yield and stability to ensure accurate probe characterization. Additionally, we assessed the probe's affinity and specificity toward the CLDN18.2 target and evaluated its efficacy in the BGC82318.2 xenograft model for SPECT/CT imaging of gastric cancer. The binding of [99mTc]Tc-PHG102 to HEK-293T18.2 and BGC82318.2 cells was notably higher than its binding to HEK-293T18.1, HEK-293T, and BGC823 cells, with bound values of 12.87 ± 1.46%, 6.16 ± 0.34%, 1.25 ± 0.22%, 1.14 ± 0.26%, and 1.32 ± 0.07% AD, respectively. The binding ability of [99mTc]Tc-PHG102 was significantly different between CLDN18.2-positive and negative cells (P < 0.001). Imaging results demonstrated a time-dependent tumor accumulation of the radiotracer. Notably, at 0.5 h postinjection, rapid accumulation was observed with an average tumor uptake of 4.63 ± 0.81% ID/cc (n = 3), resulting in clear tumor visualization. By 1 h postinjection, as [99mTc]Tc-PHG102 was rapidly metabolized, a decrease in uptake by other organs was noted. Preliminary clinical imaging trials further confirmed the safety and effectiveness of the probe, indicating specificity for lesions expressing CLDN18.2 in gastric cancer and favorable in vivo metabolic properties. In conclusion, the nanobody-based probe [99mTc]Tc-PHG102 proves to be a safe and effective tool for detecting CLDN18.2 expression levels in gastric cancer tumors and for screening CLDN18.2-positive patients.

16.
Curr Pharm Des ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39129280

RESUMEN

INTRODUCTION: Macrophage dysregulation is a common pathogenic feature of viruses that provides extensive targets for antiviral therapy. Nobiletin, a polymethoxylated flavonoid found in citrus fruits, has a multitude of effects. METHODS: We investigated the effect of nobiletin on polyinosinic-polycytidylic acid (poly(I:C))-induced inflammation in RAW264.7 cells. Nobiletin inhibited the production of poly(I:C)-induced inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and CXCL10. High-throughput sequencing revealed that nobiletin inhibited the expression of TNF-α, IL-6, and CXCL10 and promoted the expression of CD206, Chil3, and Vcam1. In the Kyoto Encyclopedia of Genes and Genomes enrichment analyses, the upregulated differential genes were significantly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. RESULTS: The PPAR-γ inhibitor T0070907 significantly reversed the inhibitory effects of nobiletin on IL-6 and CXCL10 but had no significant effect on TNF-α secretion. CONCLUSION: Thus, nobiletin regulated poly(I:C)-induced inflammatory responses in RAW264.7 cells partially via the PPAR-γ signaling pathway.

17.
Carbon Balance Manag ; 19(1): 19, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38884686

RESUMEN

The changes and influencing factors of soil inorganic carbon (SIC) and organic carbon (SOC) on precipitation gradients are crucial for predicting and evaluating carbon storage changes at the regional scale. However, people's understanding of the distribution characteristics of SOC and SIC reserves on regional precipitation gradients is insufficient, and the main environmental variables that affect SOC and SIC changes are also not well understood. Therefore, this study focuses on the Alxa region and selects five regions covered by three typical desert vegetation types, Zygophyllum xanthoxylon (ZX), Nitraria tangutorum (NT), and Reaumuria songarica (RS), along the climate transect where precipitation gradually increases. The study analyzes and discusses the variation characteristics of SOC and SIC under different vegetation and precipitation conditions. The results indicate that both SOC and SIC increase with the increase of precipitation, and the increase in SOC is greater with the increase of precipitation. The average SOC content in the 0-300cm profile is NT (4.13 g kg-1) > RS (3.61 g kg-1) > ZX (3.57 g kg-1); The average value of SIC content is: RS (5.78 g kg-1) > NT (5.11 g kg-1) > ZX (5.02 g kg-1). Overall, the multi-annual average precipitation (MAP) in the Alxa region is the most important environmental factor affecting SIC and SOC.

18.
ACS Appl Mater Interfaces ; 16(2): 2438-2448, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38180810

RESUMEN

The large grain boundary resistance between different components of the anode electrode easily leads to the low ion transport efficiency and poor electrochemical performance of lithium-/sodium-ion batteries (LIBs/SIBs). To address the issue, a Janus heterointerface with a Mott-Schottky structure is proposed to optimize the interface atomic structure, weaken interatomic resistance, and improve ion transport kinetics. Herein, Janus Co/Co2P@carbon-nanotubes@core-shell (Janus Co/Co2P@CNT-CS) refined urchin-like architecture derived from metal-organic frameworks is reported via a coating-phosphating process, where the Janus Co/Co2P heterointerface nanoparticles are confined in carbon nanotubes and a core-shell polyhedron. Such a Janus Co/Co2P heterointerface shows the strong built-in electric field, facilitating the controllable ion transport channels and the high ion transport efficiency. The Janus Co/Co2P@CNT-CS refined urchin-like architecture composed of a core-shell structure and the grafting carbon nanotubes enhances the structure stability and electronic conductivity. Benefiting from the spaced-confined Janus heterointerface engineering and synergistic effects between the core-shell structure and the grafting carbon nanotubes, the Janus Co/Co2P@CNT-CS refined urchin-like architecture demonstrates the fast ion transport rate and excellent pseudocapacitance performance for LIBs/SIBs. In this case, the Janus Co/Co2P@CNT-CS refined urchin-like architecture shows high specific capacities of 709 mA h g-1 (200 cycles) and 203 mA h g-1 (300 cycles) at a current density of 500 mA g-1 for LIBs/SIBs, respectively.

19.
Plants (Basel) ; 13(2)2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38276764

RESUMEN

Drought and high-temperature stress are the main abiotic stresses that alone or simultaneously affect the yield and quality of pears worldwide. However, studies on the mechanisms of drought or high-temperature resistance in pears remain elusive. Therefore, the molecular responses of Pyrus betuleafolia, the widely used rootstock in pear production, to drought and high temperatures require further study. Here, drought- or high-temperature-resistant seedlings were selected from many Pyrus betuleafolia seedlings. The leaf samples collected before and after drought or high-temperature treatment were used to perform RNA sequencing analysis. For drought treatment, a total of 11,731 differentially expressed genes (DEGs) were identified, including 4444 drought-induced genes and 7287 drought-inhibited genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these DEGs were more significantly enriched in plant hormone signal transduction, flavonoid biosynthesis, and glutathione metabolism. For high-temperature treatment, 9639 DEGs were identified, including 5493 significantly upregulated genes and 4146 significantly downregulated genes due to high-temperature stress. KEGG analysis showed that brassinosteroid biosynthesis, arginine metabolism, and proline metabolism were the most enriched pathways for high-temperature response. Meanwhile, the common genes that respond to both drought and high-temperature stress were subsequently identified, with a focus on responsive transcription factors, such as MYB, HSF, bZIP, and WRKY. These results reveal potential genes that function in drought or high-temperature resistance. This study provides a theoretical basis and gene resources for the genetic improvement and molecular breeding of pears.

20.
Sci Rep ; 14(1): 16910, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043783

RESUMEN

The characteristics and heterogeneity of coal pores are crucial for understanding the production mechanism of coalbed methane (CBM). In this study, coal samples with varying degrees of metamorphism (0.58% ≤ RO, max ≤ 3.44%) were collected. The characteristics of pore development and the heterogeneous properties of pores were revealed through low-temperature nitrogen adsorption (LTNA) and low-field nuclear magnetic resonance (NMR) experiments. The results indicate that pores with varying diameters exhibit favorable development in low-rank coals, along with favorable pores connectivity. The micropores composition of middle-rank coals was found to be 73.56%, however, the connectivity among transitional, meso, and macropores was observed to be poor. In high-rank coals, the proportion of micropores was 92.74%, with numerous micropores being closed or semi-closed. This resulted in inferior connectivity between micropores and transitional pores. As coal metamorphism progressed, the DL1 (characterizing the roughness of adsorption pores (AP) surface, ranging from 2.13 to 2.45) and DL2 (characterizing the complexity of AP structure, ranging from 2.56 to 2.77) initially decreased and then increased, whereas the DN (characterizing the heterogeneity of seepage pores (SP), ranging from 2.92 to 2.95) consistently improved. Furthermore, the roughness of pore surface and the complexity of pore structure in AP increased as the specific surface area and volume of pores increased. On the contrary, as the SP content increased, the uniformity of the pore structure improved. When the volume of SP remained constant, the complexity of the pore structure decreased due to increased pore connectivity.

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