Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 571
Filtrar
1.
Bioorg Chem ; 151: 107700, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39128245

RESUMO

A series of pyrimidine-2,4-diamine analogues were designed and synthesized. Their anticancer activity and the underlying mechanism against colorectal cancer (CRC) HCT116 cells and non-small cell lung cancer (NSCLC) A549 cells were investigated. The results demonstrated that the active compound Y18 significantly inhibited cancer cell proliferation by inducing robust cell cycle arrest and cell senescence through the persistence of DNA damage. Additionally, Y18 exhibited significant inhibitory effects on the adhesion, migration and invasion of cancer cells in vitro. Mechanistically, Y18 achieved these anticancer activities by suppressing GTSE1 transcription and expression. Y18 also effectively inhibited tumor growth in vivo with minimal side effects. Furthermore, Y18 exhibited a suitable half-life and oral bioavailability (16.27%), with limited inhibitory activity on CYP isoforms. Taken together, these results suggested that Y18 could be a potential chemotherapeutic drug for cancer treatment, particularly in cases of GTSE1 overexpressed cancers.

2.
PLoS One ; 19(8): e0307280, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39146329

RESUMO

Proposed is a Satellite network cache placement strategy (PNCCP) based on popularity and node cooperation to address the issue of significant delays in end-to-end connectivity due to instability among satellites. Initially, the strategy employs spectral clustering algorithm to partition the satellite network's topology, limiting the retrieval scope of content and reducing unnecessary propagation delays. Within each partition, a cache collaboration open mechanism among satellites is devised to share cache resources, utilizing the proximity of neighboring nodes to share popular content and cache space. Furthermore, the data naming network (NDN) cache model is enhanced and integrated with the open mechanism, with an update mechanism designed to address the invalidation caused by the dynamic nature of satellite networks. Finally, aiming to minimize users' average retrieval delay, the artificial bee colony algorithm is employed to solve the optimal cache placement problem. Simulation results demonstrate that compared to three contrasting cache strategies, the proposed strategy reduces user content retrieval delays, improves cache hit rates, and holds an advantage in reducing request hop counts.


Assuntos
Algoritmos , Redes de Comunicação de Computadores , Simulação por Computador , Humanos , Modelos Teóricos
3.
J Environ Manage ; 367: 121979, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39088904

RESUMO

Cadmium (Cd) is readily absorbed by tobacco and accumulates in the human body through smoke inhalation, posing threat to human health. While there have been many studies on the negative impact of cadmium in tobacco on human health, the specific adaptive mechanism of tobacco roots to cadmium stress is not well understood. In order to comprehensively investigate the effects of Cd stress on the root system of tobacco, the combination of transcriptomic, biochemical, and physiological methods was utilized. In this study, tobacco growth was significantly inhibited by 50 µM of Cd, which was mainly attributed to the destruction of root cellular structure. By comparing the transcriptome between CK and Cd treatment, there were 3232 up-regulated deferentially expressed genes (DEGs) and 3278 down-regulated DEGs. The obvious differential expression of genes related to the nitrogen metabolism, metal transporters and the transcription factors families. In order to mitigate the harmful effects of Cd, the root system enhances Cd accumulation in the cell wall, thereby reducing the Cd content in the cytoplasm. This result may be mediated by plant hormones and transcription factor (TF). Correlational statistical analysis revealed significant negative correlations between IAA and GA with cadmium accumulation, indicated by correlation coefficients of -0.91 and -0.93, respectively. Conversely, ABA exhibited a positive correlation with a coefficient of 0.96. In addition, it was anticipated that 3 WRKY TFs would lead to a reduction in Cd accumulation. Our research provides a theoretical basis for the systematic study of the specific physiological processes of plant roots under Cd stress.


Assuntos
Cádmio , Reguladores de Crescimento de Plantas , Fatores de Transcrição , Transcriptoma , Cádmio/toxicidade , Cádmio/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Transcriptoma/efeitos dos fármacos , Reguladores de Crescimento de Plantas/metabolismo , Nicotiana/genética , Nicotiana/efeitos dos fármacos , Estresse Fisiológico , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos
4.
Plant Foods Hum Nutr ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150636

RESUMO

The fruit of the jujube tree is high in nutrients and has various health benefits. China is a major producer of jujube, and it is now cultivated all around the world. Numerous studies have demonstrated the nutritional value and potential health advantages of bioactive compounds found in the jujube tree. Furthermore, the jujube tree has a remarkable 7000-year agricultural history. The jujube plant has developed a rich gene pool, making it a valuable resource for germplasm. Different studies have focused on the developmental stages of jujube fruits to identify the optimal time for harvest and to assess the changes in their bioactive natural compounds or products during the process of development but the molecular mechanism underlying the production of bioactive natural products in Z. jujuba is still poorly understood. Moreover, the potential differential expressed genes (DEGs) identified as responsible for the synthesis of these compounds should be further functionally verified. It has been noticed that the contents of total flavonoids, total phenolic, and vitamin C increase significantly during the ripening process, while the contents of soluble sugars and organic acids decrease gradually. In this review, we have also scrutinized the challenges that hinder the utilization of jujube fruit resources and suggested potential areas for further research. As such, our review serves as a valuable resource for the future development of jujube-based nutritional compounds and the incorporation of their nutritional elements into the functional foods industry.

5.
Plant Cell Environ ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39119795

RESUMO

Phytoplasmas can induce complex and substantial phenotypic changes in their hosts in ways that favour their colonisation, but the mechanisms underlying these changes remain largely unknown. Jujube witches' broom (JWB) disease is a typical phytoplasma disease causing great economic loss in Chinese jujube (Ziziphus jujuba Mill.). Here, we reported an effector, PHYL1JWB from Candidatus Phytoplasma ziziphi, which implicated in inducing abnormal floral organogenesis. Utilising a combination of in vivo and in vitro methods, we investigated the influence of PHYL1JWB on the proteins associated with floral development. Our findings reveal that PHYL1JWB facilitates the proteasome-mediated degradation of essential flower morphogenetic regulators, including AP1, SEP1, SEP2, SEP3, SEP4, CAL, and AGL6, through a distinctive pathway that is dependent on the activity of the 26S proteasome, thus obviating the requirement for lysine ubiquitination of the substrates. Further, the Y2H analysis showed that the leucine at position 75th in second α helix of PHYL1JWB is fundamental for the interactions of PHYL1JWB with AP1 and SEP1-4 in jujube and Arabidopsis. Our research carry profound implications for elucidating the contribution of PHYL1JWB to the aberrant floral development in diseased jujube, and help to establish a robust theoretical underpinning for the prophylaxis and therapy of JWB disease.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38972436

RESUMO

BACKGROUND: There are limited clinical data regarding the additional yields of random biopsies (RBs) during colorectal cancer surveillance in patients with inflammatory bowel disease. To assess the additional yield of RB, a systematic review and meta-analysis was conducted. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies investigating the preferred colonoscopy surveillance approach for inflammatory bowel disease patients. The additional yield, detection rate, procedure time, and withdrawal time were pooled. RESULTS: Thirty-seven studies (48 arms) were included in the meta-analysis with 9051 patients. The additional yields of RB were 10.34% in per-patient analysis and 16.20% in per-lesion analysis. The detection rates were 1.31% and 2.82% in per-patient and per-lesion analysis, respectively. Subgroup analysis showed a decline in additional yields from 14.43% to 0.42% in the per-patient analysis and from 19.20% to 5.32% in the per-lesion analysis for studies initiated before and after 2011. In per-patient analysis, the additional yields were 4.83%, 10.29%, and 56.05% for primary sclerosing cholangitis (PSC) proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 0.56%, 1.40%, and 19.45%. In the per-lesion analysis, additional yields were 11.23%, 21.06%, and 45.22% for PSC proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 2.09%, 3.58%, and 16.24%. CONCLUSIONS: The additional yields of RB were 10.34% and 16.20% for per-patient and per-lesion analyses, respectively. Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating RB in the standard colonoscopy surveillance for inflammatory bowel disease patients, especially in those with PSC.

7.
Plant Physiol Biochem ; 215: 108977, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39084167

RESUMO

Silicon (Si) can significantly improve the salt tolerance of plants, but its mechanism remains unclear. In this study, role of abscisic acid (ABA) in Si derived salt resistance in tobacco seedling was investigated. Under salt stress, the photosynthetic rate, stomatal conductance, and transpiration rate of tobacco seedlings were reduced by 86.17%, 80.63%, and 67.54% respectively, resulting in a decrease in biomass. The application of Si found to mitigate these stress-induced markers. However, positive role of Si was mainly attributed to the enhanced expression of aquaporin genes, which helped in enhancing root hydraulic conductance (Lpr) and ultimately maintaining the leaf relative water content (RWC). Moreover, sodium tungstate, an ABA biosynthesis inhibitor, was used to test the role of ABA on Si-regulating Lpr. The results indicated that the improvement of Lpr by Si was diminished in the presence of ABA inhibitor. In addition, it was observed that the ABA content was increased due to the Si-upregulated of ABA biosynthesis genes, namely NtNCED1 and NtNCED5. Conversely, the expression of ABA metabolism gene NtCYP7O7A was found to be reduced by Si. Together, this study suggested that Si increased ABA content, leading to enhanced efficiency of water uptake by the roots, ultimately facilitating an adequate water supply to maintain leaf water balance. As a result, there was an improvement in salt resistance in tobacco seedling.

8.
Sci Rep ; 14(1): 16315, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009661

RESUMO

In this article, we investigated the solitary wave solutions of the KdV-mKdV equation using Hirota's bilinear method. Closed-form analytical single and multiple solitary wave solutions were obtained. Through qualitative methods and the analysis of solitary waveforms, we discovered that in addition to sech-type solitary waves, the system also contains Sech 2 -type solitary waves. By employing the trial functions method, we obtained a single Sech 2 -type solitary wave and verified its existence and stability using the split-Step Fourier Transform method. Furthermore, we use the collision of two Sech 2 -type single solitary waves to excite a stable Sech 2 -type double solitary wave. Similarly, we excite a stable triple solitary wave with three Sech 2 -type single solitary waves. This method can also be used to excite stable multiple solitary waves. It is shown that these solitary wave solutions enrich the dynamic behavior of the KdV-mKdV equation and provide methods for solving Sech 2 -type solitary waves, which hold significant theoretical value.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38904989

RESUMO

TwoGram-stain-positive and rod-shaped actinomycetes (strains CDC186T and CDC192) were isolated from sputum samples of a patient in Chongqing, PR China, and were investigated to determine their taxonomic status. The results of phylogenetic analysis based on the 16S rRNA gene indicated that CDC186T and CDC192 represented members of the genus Nocardia, and the sequence similarity with Nocardia beijingensis DSM 44636T was the highest, at 99.71 and 99.78 %, respectively. The DNA G+C content of both CDC186T and CDC192 was 69.1 %. Genomic diversity analysis revealed that the average nucleotide identity and in silico DNA‒DNA hybridisation values between the two novel strains and closely related species were significantly below the thresholds of 95-96 and 70 %, respectively, but these values between the two novel strains were 99.96 and 99.90 %, respectively. The phylogenetic relationship based on the dapb1 gene and the single-copy core genes further indicated that the two novel strains were clustered in separate branch adjacent to N. beijingensis DSM 44636T. Growth occurred within the ranges of 20-42 °C, pH 6.0-9.0 and NaCl concentrations of 0.5-4.5 % (w/v). The major fatty acids of CDC186T and CDC192 were C16 : 0 and C18 : 0 10-methyl [tuberculostearic acid (TBSA)]. The predominant respiratory menaquinone was MK-9. The polar lipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannoside, one unidentified glycolipid, one unidentified phospholipid and one unidentified phosphoglycolipid. All the genomes of the studied strains were annotated with virulence factor (VF)-associated genes homologous to those of Mycobacterium tuberculosis, and the results of susceptibility testing indicated that CDC186T and CDC192 were resistant to amoxicillin-clavulanic acid and tigecycline. On the basis of chemotaxonomic characteristics and the results of phylogenetic analyses, strains CDC186T and CDC192 represent a novel species within the genus Nocardia, for which the name Nocardia implantans sp. nov. is proposed. The type strain is CDC186T (=GDMCC 4.206T= JCM 34959T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Nocardiose , Nocardia , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Escarro , Nocardia/isolamento & purificação , Nocardia/genética , Nocardia/classificação , Humanos , RNA Ribossômico 16S/genética , China , DNA Bacteriano/genética , Ácidos Graxos/análise , Ácidos Graxos/química , Nocardiose/microbiologia , Escarro/microbiologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Genoma Bacteriano
10.
Elife ; 132024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904661

RESUMO

The success of an organism depends on the molecular and ecological adaptations that promote its beneficial fitness. Parasitoids are valuable biocontrol agents for successfully managing agricultural pests, and they have evolved diversified strategies to adapt to both the physiological condition of hosts and the competition of other parasitoids. Here, we deconstructed the parasitic strategies in a highly successful parasitoid, Trichopria drosophilae, which parasitizes a broad range of Drosophila hosts, including the globally invasive species D. suzukii. We found that T. drosophilae had developed specialized venom proteins that arrest host development to obtain more nutrients via secreting tissue inhibitors of metalloproteinases (TIMPs), as well as a unique type of cell-teratocytes-that digest host tissues for feeding by releasing trypsin proteins. In addition to the molecular adaptations that optimize nutritional uptake, this pupal parasitoid has evolved ecologically adaptive strategies including the conditional tolerance of intraspecific competition to enhance parasitic success in older hosts and the obligate avoidance of interspecific competition with larval parasitoids. Our study not only demystifies how parasitoids weaponize themselves to colonize formidable hosts but also provided empirical evidence of the intricate coordination between the molecular and ecological adaptations that drive evolutionary success.


Assuntos
Adaptação Fisiológica , Drosophila , Interações Hospedeiro-Parasita , Vespas , Animais , Vespas/fisiologia , Drosophila/parasitologia , Pupa/parasitologia , Larva/parasitologia , Larva/metabolismo
11.
Sci Rep ; 14(1): 12950, 2024 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839805

RESUMO

Endophytes have been shown to promote plant growth and health. In the present study, a Bacillus velezensis CH1 (CH1) strain was isolated and identified from high-quality oats, which was capable of producing indole-3-acetic acid (IAA) and strong biofilms, and capabilities in the nitrogen-fixing and iron carriers. CH1 has a 3920 kb chromosome with 47.3% GC content and 3776 code genes. Compared genome analysis showed that the largest proportion of the COG database was metabolism-related (44.79%), and 1135 out of 1508 genes were associated with the function "biosynthesis, transport, and catabolism of secondary metabolites." Furthermore, thirteen gene clusters had been identified in CH1, which were responsible for the synthesis of fifteen secondary metabolites that exhibit antifungal and antibacterial properties. Additionally, the strain harbors genes involved in plant growth promotion, such as seven putative genes for IAA production, spermidine and polyamine synthase genes, along with multiple membrane-associated genes. The enrichment of these functions was strong evidence of the antimicrobial properties of strain CH1, which has the potential to be a biofertilizer for promoting oat growth and disease resistance.


Assuntos
Avena , Bacillus , Ácidos Indolacéticos , Bacillus/genética , Bacillus/metabolismo , Bacillus/isolamento & purificação , Avena/microbiologia , Avena/crescimento & desenvolvimento , Ácidos Indolacéticos/metabolismo , Biofilmes/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Fixação de Nitrogênio , Filogenia , Endófitos/isolamento & purificação , Endófitos/metabolismo , Endófitos/genética , Genoma Bacteriano
12.
J Nutr ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880175

RESUMO

BACKGROUND: The incongruity between dietary patterns and the circadian clock poses an elevated risk for metabolic health issues, particularly obesity and associated metabolic disorders. The intestinal microflora engages in regulating various physiological functions of the host through its metabolites. OBJECTIVES: This study aimed to investigate the impact of reversed feeding schedules during the day and night on intestinal flora and lipid metabolism in high-fat diet-induced obese mice. METHODS: Mice aged 8-10 wk were subjected to either daytime or nighttime feeding and were administered a control or high-fat diet for 18 wk. At the end of the experiment, various assessments were conducted, including analysis of serum biochemic indices, histologic examination, evaluation of gene and protein expression in adipose tissue, and scrutiny of changes in intestinal microbial composition. RESULTS: The results showed that day-night reversed feeding caused an increase in fasting blood glucose and exacerbated the high-fat diet-induced weight gain and lipid abnormalities. The mRNA expression levels of Leptin and Dgat1 were increased by day-night reversed feeding, which also reduced the expression level of adiponectin under the high-fat diet. Additionally, there was a significant increase in the protein concentrations of PPARγ, SREBP1c, and CD36. Inverted feeding schedules led to a reduction in intestinal microbial diversity, an increase in the abundance of inflammation-related bacteria, such as Coriobacteriaceae_UCG-002, and a suppression of beneficial bacteria, including Akkermansia, Candidatus_Saccharimonas, Anaeroplasma, Bifidobacterium, Carnobacterium, and Odoribacter. Acinetobacter exhibited a significant negative correlation with Leptin and Fasn, suggesting potential involvement in the regulation of lipid metabolism. CONCLUSIONS: The results elucidated the abnormalities of lipid metabolism and intestinal flora caused by day-night reversed feeding, which exacerbates the adverse effects of a high-fat diet on lipid metabolism and intestinal microflora. This reversal in feeding patterns may disrupt both intestinal and lipid metabolism homeostasis by altering the composition and abundance of intestinal microflora in mice.

13.
Ecotoxicol Environ Saf ; 281: 116596, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38896899

RESUMO

Cadmium (Cd), which accumulates in tobacco leaves, enters the human body through inhalation of smoke, causing harmful effects on health. Therefore, identifying the pivotal factors that govern the absorption and resistance of Cd in tobacco is crucial for mitigating the harmful impact of Cd. In the present study, four different Cd-sensitive varieties, namely, ZhongChuan208 (ZC) with resistance, ZhongYan100 (ZY), K326 with moderate resistance, and YunYan87 (YY) with sensitivity, were cultivated in hydroponic with different Cd concentrations (20 µM, 40 µM, 60 µM and 80 µM). The results indicated that plant growth was significantly decreased by Cd. Irrespective of the Cd concentration, ZC exhibited the highest biomass, while YY had the lowest biomass; ZY and K326 showed intermediate levels. Enzymatic (APX, CAT, POD) and nonenzymatic antioxidant (Pro, GSH) systems showed notable variations among varieties. The multifactor analysis suggested that the ZC and ZY varieties, with higher levels of Pro and GSH content, contribute to a decrease in the levels of MDA and ROS. Among all the Cd concentrations, ZC exhibited the lowest Cd accumulation, while YY showed the highest. Additionally, there were significant differences observed in Cd distribution and translocation factors among the four different varieties. In terms of Cd distribution, cell wall Cd accounted for the highest proportion of total Cd, and organelles had the lowest proportion. Among the varieties, ZC showed lower Cd levels in the cell wall, soluble fraction, and organelles. Conversely, YY exhibited the highest Cd accumulation in all tissues; K326 and ZY had intermediate levels. Translocation factors (TF) varied among the varieties under Cd stress, with ZC and ZY showing lower TF compared to YY and K326. This phenomenon mainly attributed to regulation of the NtNramp3 and NtNramp5 genes, which are responsible for the absorption and transport of Cd. This study provides a theoretical foundation for the selection and breeding of tobacco varieties that are resistant to or accumulate less Cd.


Assuntos
Nicotiana , Nicotiana/química , Nicotiana/genética , Nicotiana/crescimento & desenvolvimento , Nicotiana/metabolismo , Cádmio/toxicidade , Resistência a Medicamentos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Antioxidantes/metabolismo , Proteínas de Transporte de Cátions/metabolismo
14.
J Hazard Mater ; 476: 134905, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38941827

RESUMO

Numerous studies shown that silicon (Si) enhanced plants' resistance to cadmium (Cd). Most studies primarily focused on investigating the impact of Si on Cd accumulation. However, there is a lack of how Si enhanced Cd resistance through regulation of water balance. The study demonstrated that Si had a greater impact on increasing fresh weight compared to dry weight under Cd stress. This effect was mainly attributed to Si enhanced plant relative water content (RWC). Plant water content depends on the dynamic balance of water loss and water uptake. Our findings revealed that Si increased transpiration rate and stomatal conductance, leading to higher water loss. This, in turn, negatively impacted water content. The increased water content caused by Si could ascribe to improve root water uptake. The Si treatment significantly increased root hydraulic conductance (Lpr) by 131 % under Cd stress. This enhancement was attributed to Si upregulation genes expression of NtPIP1;1, NtPIP1;2, NtPIP1;3, and NtPIP2;1. Through meticulously designed scientific experiments, this study showed that Si enhanced AQP activity, leading to increased water content that diluted Cd concentration and ultimately improved plant Cd resistance. These findings offered fresh insights into the role of Si in bolstering plant resistance to Cd.


Assuntos
Aquaporinas , Cádmio , Nicotiana , Raízes de Plantas , Plântula , Silício , Água , Cádmio/toxicidade , Silício/farmacologia , Silício/química , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Plântula/efeitos dos fármacos , Plântula/metabolismo , Nicotiana/efeitos dos fármacos , Nicotiana/metabolismo , Aquaporinas/metabolismo , Água/química , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Transpiração Vegetal/efeitos dos fármacos
15.
Artigo em Inglês | MEDLINE | ID: mdl-38713298

RESUMO

PURPOSE: The unsatisfactory efficacy of PD-L1 antibodies in glioblastoma (GBM) is largely due to the temporal and spatial heterogeneity of PD-L1 expression. Molecular imaging can enhance understanding of the tumor immune microenvironment and guide immunotherapy. However, highly sensitive imaging agents capable of effectively visualizing PD-L1 heterogeneity are limited. This study introduces a novel PET tracer, offering improved imaging of PD-L1 heterogeneity in GBM xenografts, with a comparative analysis to [18F]AlF-NOTA-WL12. METHODS: [18F]AlF-NOTA-PCP2 was synthesized with high purity and its affinity for PD-L1 was characterized using surface plasmon resonance (SPR) and cell binding assays. Its specificity for PD-L1 was evaluated both in vitro using various cell lines and in vivo with GBM xenograft models in NOD/SCID mice. PET/CT imaging was conducted to evaluate the tracer's biodistribution, pharmacokinetics, and ability to quantify tumoral spatial heterogeneity of PD-L1 expression. A focused comparative analysis between [18F]AlF-NOTA-PCP2 and [18F]AlF-NOTA-WL12 was conducted, examining binding affinity, biodistribution, pharmacokinetics, and imaging effectiveness in GBM xenografts. Additionally, human radiation dosimetry estimates compared the safety profiles of both tracers. RESULTS: [18F]AlF-NOTA-PCP2 demonstrated high radiochemical purity (> 95%) and a strong affinity for PD-L1, comparable to [18F]AlF-NOTA-WL12. In vitro and in vivo studies confirmed its specificity for PD-L1, with increased uptake in PD-L1 expressing cells and tumors. Toxicological profiles indicated no significant abnormalities in serum biochemical indicators or major organ tissues. MicroPET/CT imaging showed [18F]AlF-NOTA-PCP2's effectiveness in visualizing PD-L1 expression levels and spatial heterogeneity in GBM xenografts. Comparative studies revealed [18F]AlF-NOTA-PCP2's improved pharmacokinetic properties, including higher tumor-to-blood ratios and lower nonspecific liver uptake, as well as reduced radiation exposure compared to [18F]AlF-NOTA-WL12. CONCLUSION: [18F]AlF-NOTA-PCP2 distinguishes itself as an exceptionally sensitive PET/CT tracer, adept at non-invasively and accurately quantifying PD-L1 expression and its spatial heterogeneity in tumors, especially in GBM. Its favorable pharmacokinetic properties, safety profile, and high affinity for PD-L1 highlight its potential for enhancing the precision of cancer immunotherapy and guiding individualized treatment strategies. While promising, its clinical translation, especially in brain imaging, necessitates further validation in clinical trials.

16.
BMC Biol ; 22(1): 113, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750524

RESUMO

BACKGROUND: Protein posttranslational modifications (PTMs) are fast and early responses to environmental changes, including pathogen infection. Jujube witches' broom (JWB) is a phytoplasma disease causing great economic loss in jujube production. After phytoplasma infection, the transcriptional, translational, and metabolic levels in jujube were activated, enabling it to survive during phytoplasma invasion. However, no study has yet reported on PTMs in jujube. Lysine crotonylation (Kcr) and lysine succinylation (Ksu) have been popular studies in recent years and their function in plant phytoplasma-stress responses remains unclear. RESULTS: Here, 1656 crotonylated and 282 succinylated jujube proteins were first identified under phytoplasma-stress, of which 198 were simultaneously crotonylated and succinylated. Comparative analysis revealed that 656 proteins, 137 crotonylated and 43 succinylated proteins in jujube were regulated by phytoplasma infection, suggesting that Kcr was more universal than Ksu. Kcr differentially expressed proteins (DEPs) were related to ribosomes, photosynthetic and carbon metabolism, while Ksu DEPs were mainly involved in carbon metabolism, the TCA cycle and secondary metabolite biosynthesis. The crosstalk network among proteome, crotonylome and succinylome showed that DEPs related to ribosomal, peroxidases and glutathione redox were enriched. Among them, ZjPOD51 and ZjPHGPX2 significantly increased at the protein and Kcr level under phytoplasma-stress. Notably, 7 Kcr sites were identified in ZjPHGPX2, a unique antioxidant enzyme. After inhibitor nicotinamide (NAM) treatment, GPX enzyme activity in jujube seedlings was reduced. Further, site-directed mutagenesis of key Kcr modification sites K130 and/or K135 in ZjPHGPX2 significantly reduced its activity. CONCLUSIONS: This study firstly provided large-scale datasets of Kcr and Ksu in phytoplasma-infected jujube and revealed that Kcr modification in ZjPHGPX2 positively regulates its activity.


Assuntos
Phytoplasma , Doenças das Plantas , Proteínas de Plantas , Ziziphus , Ziziphus/microbiologia , Ziziphus/metabolismo , Phytoplasma/fisiologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Doenças das Plantas/microbiologia , Processamento de Proteína Pós-Traducional , Estresse Fisiológico , Lisina/metabolismo
17.
Plant Physiol Biochem ; 211: 108679, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38714127

RESUMO

Cold stress is a limiting stress factor that limits plant distribution and development; however, polyploid plants have specific characteristics such as higher resistance to abiotic stress, especially cold stress, that allow them to overcome this challenge. The cultivated cultivar Ziziphus jujuba Mill. 'Yueguang' (YG) and its autotetraploid counterpart 'Hongguang' (HG) exhibit differential cold tolerance. However, the underlying molecular mechanism and methods to enhance their cold tolerance remain unknown. Anatomical structure and physiological analysis indicated YG had a higher wood bark ratio, and xylem ratio under cold treatment compared to HG. However, the half-lethal temperature (LT50), cortex ratio, and malondialdehyde (MDA) content were significantly decreased in YG than HG, which indicated YG was cold tolerant than HG. Transcriptome analysis showed that 2084, 1725, 2888, and 2934 differentially expressed genes (DEGs) were identified in HC vs YC, H20 vs Y20, Y20 vs YC, and H20 vs HC treatment, respectively. Meanwhile, KEGG enrichment analysis of DEGs showed that several metabolic pathways, primarily plant hormone signal transduction and the MAPK signaling pathway, were involved in the differential regulation of cold tolerance between YG and HG. Furthermore, exogenous abscisic acid (ABA) and brassinolide (BR) treatments could improve their cold tolerance through increased SOD and POD activities, decreased relative electrical conductivity, and MDA content. All of these findings suggested that plant hormone signal transduction, particularly ABA and BR, might have an important role in the regulation of differential cold tolerance between YG and HG, laying the foundation for further improving cold tolerance in jujube and examining the molecular mechanisms underlying differences in cold tolerance among different ploidy cultivars.


Assuntos
Resposta ao Choque Frio , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Ziziphus , Ziziphus/genética , Ziziphus/fisiologia , Ziziphus/metabolismo , Resposta ao Choque Frio/genética , Transcriptoma/genética , Temperatura Baixa , Malondialdeído/metabolismo
18.
Sci Rep ; 14(1): 11506, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769108

RESUMO

The optimal design of groundwater circulation wells (GCWs) is challenging. The key to purifying groundwater using this technique is its proficiency and productivity. However, traditional numerical simulation methods are limited by long modeling times, random optimization schemes, and optimization results that are not comprehensive. To address these issues, this study introduced an innovative approach for the optimal design of a GCW using machine learning methods. The FloPy package was used to create and implement the MODFLOW and MODPATH models. Subsequently, the formulated models were employed to calculate the characteristic indicators of the effectiveness of the GCW operation, including the radius of influence (R) and the ratio of particle recovery (Pr). A detailed collection of 3000 datasets, including measures of operational efficiency and key elements in machine learning, was meticulously compiled into documents through model execution. The optimization models were trained and evaluated using multiple linear regression (MLR), artificial neural networks (ANN), and support vector machines (SVM). The models produced by the three approaches exhibited notable correlations between anticipated outcomes and datasets. For the optimal design of circulating well parameters, machine learning methods not only improve the optimization speed, but also expand the scope of parameter optimization. Consequently, these models were applied to optimize the configuration of the GCW at a site in Xi'an. The optimal scheme for R (Q = 293.17 m3/d, a = 6.09 m, L = 7.28 m) and optimal scheme for Pr (Q = 300 m3/d, a = 3.64 m, L = 1 m) were obtained. The combination of numerical simulations and machine learning is an effective tool for optimizing and predicting the GCW remediation effect.

19.
Heliyon ; 10(9): e30276, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38711667

RESUMO

Investigating oat tissue microflora during its different developmental stages is necessary for understanding its growth and anti-disease mechanism. In this study, 16S rDNA and ITS (Internally Transcribed Spacer) high-throughput sequencing technology were used to explore the microflora diversity of oat tissue. Twenty-seven samples of leaves, stems, and roots from three developmental stages, namely the seedling stage (SS), jointing stage (JS), and maturity stage (MS), underwent sequencing analysis. The analysis showed that 6480 operational taxonomic units (OTUs) were identified in the examined samples, of which 1698 were fungal and 4782 were bacterial. Furthermore, 126 OTUs were shared by fungi, mainly Ascomycota, Basidiomycota, and Mucoromycota at the phylum level, and 39 OTUs were shared by bacteria, mainly Actinobacteriota and Proteobacteria at the phylum level. The microbial diversity of oat tissue in the three developmental stages showed differences, and the α-diversity of the bacteria and ß-diversity of the bacteria and fungi in the roots were higher than those of the stems and leaves. Among the bacteria species, Thiiopseudomonas, Rikenellaceae RC9 gut group, and Brevibacterium were predominant in the leaves, MND1 was predominant in the roots, and Lactobacillus was predominant in the stems. Moreover, Brevibacterium maintained a stable state at all growth stages. In the fungal species, Phomatospora was dominant in the leaves, Kondoa was dominant in the roots, and Pyrenophora was dominant in the stems. All species with a high abundance were related to the growth process of oats and antagonistic bacteria. Furthermore, connection modules were denser in bacterial than in fungal populations. The samples were treated with superoxide dismutase and peroxidase. There were 42 strains associated with SOD (Superoxide dismutase), 60 strains associated with POD (Peroxidase), and 38 strains in total, which much higher than fungi. The network analysis showed that bacteria might have more dense connection modules than fungi, The number of bacterial connections to enzymes were much higher than that of fungi. Furthermore, these results provide a basis for further mechanistic research.

20.
ACS Nano ; 18(23): 15096-15106, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38810232

RESUMO

Silicon is the cornerstone of electronics and photonics. In this context, almost all integrated devices derived from two-dimensional (2D) materials stay rooted in silicon technology. However, as the growth substrate, silicon has long been thought to be a hindrance for growing 2D materials through bottom-up methods that require high growth temperatures, and thus, indirect routes are usually considered instead. Although promising growth of large-area 2D materials on silicon has been demonstrated, the direct growth of single-crystalline materials using low-thermal-budget synthesis methods remains challenging. Here, we report the room-temperature growth of millimeter-scale single-crystal 2D metal halides on silicon substrates with a hydroxyl-terminated surface. Theoretical calculations reveal that the activation energy for surface diffusion can be reduced by an order of magnitude by terminating the surface with hydroxyl groups, from which on-silicon growth is greatly facilitated at room temperature and enables a 4-order-of-magnitude increase in area. The high quality and uniformity of the resulting single crystals are further evidenced. The optoelectronic devices employing the as-grown materials show an ultralow dark current of 10-13 A and a high detectivity of 1013 Jones, thereby corroborating a weak-light detection ability. These results would point to a rich space of surface modulation that can be used to surmount current limitations and demonstrate a promising strategy for growing 2D materials directly on silicon at room temperature to produce large single crystals.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA