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1.
Math Biosci Eng ; 21(2): 2856-2878, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38454710

RESUMO

Three-dimensional path planning refers to determining an optimal path in a three-dimensional space with obstacles, so that the path is as close to the target location as possible, while meeting some other constraints, including distance, altitude, threat area, flight time, energy consumption, and so on. Although the bald eagle search algorithm has the characteristics of simplicity, few control parameters, and strong global search capabilities, it has not yet been applied to complex three-dimensional path planning problems. In order to broaden the application scenarios and scope of the algorithm and solve the path planning problem in three-dimensional space, we present a study where five three-dimensional geographical environments are simulated to represent real-life unmanned aerial vehicles flying scenarios. These maps effectively test the algorithm's ability to handle various terrains, including extreme environments. The experimental results have verified the excellent performance of the BES algorithm, which can quickly, stably, and effectively solve complex three-dimensional path planning problems, making it highly competitive in this field.

2.
Nutrients ; 16(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38474882

RESUMO

Previous studies have shown that advanced glycation end products (AGEs) are implicated in the occurrence and progression of numerous diseases, with dietary AGEs being particularly associated with intestinal disorders. In this study, methylglyoxal-beta-lactoglobulin AGEs (MGO-ß-LG AGEs) were utilized as the exclusive nitrogen source to investigate the interaction between protein-bound AGEs and human gut microbiota. The high-resolution mass spectrometry analysis of alterations in peptides containing AGEs within metabolites before and after fermentation elucidated the capacity of intestinal microorganisms to enzymatically hydrolyze long-chain AGEs into short-chain counterparts. The 16S rRNA sequencing revealed Klebsiella, Lactobacillus, Escherichia-Shigella, and other genera as dominant microbiota at different fermentation times. A total of 187 potential strains of AGE-metabolizing bacteria were isolated from the fermentation broth at various time points. Notably, one strain of Klebsiella exhibited the most robust growth capacity when AGEs served as the sole nitrogen source. Subsequently, proteomics was employed to compare the changes in protein levels of Klebsiella X15 following cultivation in unmodified proteins and proteins modified with AGEs. This analysis unveiled a remodeled amino acid and energy metabolism pathway in Klebsiella in response to AGEs, indicating that Klebsiella may possess a metabolic pathway specifically tailored to AGEs. This study found that fermenting AGEs in healthy human intestinal microbiota altered the bacterial microbiota structure, especially by increasing Klebsiella proliferation, which could be a key factor in AGEs' role in causing diseases, particularly intestinal inflammation.


Assuntos
Produtos Finais de Glicação Avançada , Aldeído Pirúvico , Humanos , Produtos Finais de Glicação Avançada/metabolismo , RNA Ribossômico 16S , Aldeído Pirúvico/química , Bactérias/metabolismo , Nitrogênio
3.
Plants (Basel) ; 13(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38475591

RESUMO

Wx is the key gene that controls amylose content (AC), and various alleles have been found in rice populations. Wxb is the major allele in japonica and produces moderate AC (15~18%). It was recently found that editing the promoter of Wx could produce a series of alleles that have different Wx activities. Although some studies have edited the promoter, few studies have focused on the natural variations in Wx. Here, we used the Rice3K database to investigate variations in the Wx promoter and found that the allele Wx1764178 (A/G) has a higher LD (linkage disequilibrium) with the two key SNPs (1765751, T/G; 1768006, A/C), which could produce different Wx alleles and influence AC, as reported previously. Further study showed that the Wx1764178 allele (A/G) is functional and influences the expression of Wx positively. Editing the A allele using CRISPR‒Cas9 produced 36 and 3 bp deletions and caused a decrease in the expression of Wx. The apparent amylose content (AAC) in the edited lines was decreased by 7.09% and 11.50% compared with that of the wild type, which was the japonica variety Nipponbare with Wxb and the A allele at 1764178, while a complementary line with the G allele showed a lower AAC than the A allele with no effect on other agronomic traits. The AAC of the edited lines showed a higher increase than that of the wild type (Nipponbare, Wxb) in low-nitrogen conditions relative to high-nitrogen conditions. We also developed a dCAPS marker to identify the allele and found that the G allele has widely been used (82.95%) in japonica-bred varieties from Jiangsu Province, China. Overall, we found a functional allele (Wx1764178, A/G) in the Wx promoter that could affect AAC in japonica cultivars and be developed as markers for quality improvement in rice breeding programs.

4.
Huan Jing Ke Xue ; 45(2): 1049-1057, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471942

RESUMO

Risk assessment is a critical part of risk management for contaminated sites. However, in the specific management practice of As-contaminated sites, it is difficult to obtain realistic health risks for contaminated sites based on the total amount of pollutants and determined values of the model, thus preventing the control requirements of later remediation to be met. An increasing number of studies have recently been conducting risk assessments by considering bioavailability, modification parameters, and combined probabilistic models. To improve the accuracy of risk assessment results, taking a large As-contaminated site as a case, 432 sampling sites were set up and collected at different depths to analyze the level and distribution characteristics of As pollution, and probabilistic risk assessment was conducted with the modification of model parameters through literature research and Monte Carlo simulation. Then, the impact of traditional methods and probabilistic methods on health risk assessment was explored in comparison. The results indicated that ω(As) in the top soil of the study area ranged from 2.70-97.0 mg·kg-1, with a spatial variation coefficient of 0.61 and weaker spatial continuity. The carcinogenic risk and hazard index obtained by the traditional risk assessment method were 2.12E-4 and 8.36, respectively, which obviously overestimated the actual risk level and were not conductive to the refined management of As-contaminated sites. Combined with modification of model parameters and probabilistic risk assessment, the non-carcinogenic risk for adults and children was found to be at an acceptable level, and the carcinogenic risk was reduced by nearly an order of magnitude compared to that in the conventional method. Considering the relative biological effectiveness (RBA) of As, the 95% quantile of the total carcinogenic risk was 1.24E-5, a reduction of up to 36.41% compared to the uncorrected corresponding risk value of 1.95E-5. The carcinogenic risk of soil As for adults and children in the study area exceeded acceptable risk levels 1E-6, with oral ingestion of soil being the primary route of exposure. In addition, the results of the sensitivity analysis of the parameters showed that As concentration, daily oral ingestion rate of soils, and exposure duration of children had relatively larger effects for health risks. This work will provide a methodological and theoretical basis for achieving accurate risk assessment of As-contaminated sites and provide concepts for refined risk management.


Assuntos
Arsênio , Metais Pesados , Poluentes do Solo , Adulto , Criança , Humanos , Arsênio/análise , Método de Monte Carlo , Medição de Risco/métodos , Poluição Ambiental/análise , Solo , Carcinógenos/análise , Poluentes do Solo/análise , Monitoramento Ambiental , China , Metais Pesados/análise
5.
Environ Pollut ; 348: 123826, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38513941

RESUMO

As an important psychoactive substance, cotinine is ubiquitous in aquatic environment and poses a threat to aquatic organisms. However, the mechanism of its adverse health impacts remains unclear. We evaluated the effects of cotinine exposure at environmentally relevant concentrations on the development and locomotor behavior of zebrafish (Danio rerio) larvae using neurotransmitters and whole endogenous metabolism. Mild developmental toxicity and significant neurobehavior disorder, such as spontaneous movement (1-1000 µg/L), 48 hpf tactile response (50, 100, and 1000 µg/L), and 144 hpf swimming speed (1, 10, 100, 500, and 1000 µg/L), were observed in zebrafish. Exposure to cotinine led to significant alterations in 11 neurotransmitters, including homogentisic acid, serotonin, glutamic acid and aspartic acid, etc. 298 metabolites were identified and two pathways - linoleic acid metabolism and taurine and hypotaurine metabolism - were delineated. In addition, amino acid neurotransmitters were significantly correlated with metabolites such as arachidonic acid as well as its derivatives, steroidal compounds, and amino acids. Serotonin demonstrates a noteworthy correlation with 31 out of 40 differentially expressed neurotransmitters, encompassing lipids, amino acids, and other compounds. These novel findings contribute to a comprehensive understanding of the ecological risks associated with cotinine contamination in surface waters.

6.
Public Health ; 229: 144-150, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38442596

RESUMO

OBJECTIVES: The aim of this study was to evaluate the individual and combined effects of maternal smoking during pregnancy (MSDP) and personal smoking on mortality and life expectancy. STUDY DESIGN: A prospective cohort study based on the UK Biobank, with a median follow-up of 12.47 years. METHODS: This study employed multivariate Cox regression to determine the relative risks of mortality from all causes and specific diseases according to maternal and/or personal smoking status and pack-years of smoking (0, 1-20, 21-30, >30). Additionally, this study estimated the additive interaction between the two exposures. Life table analyses were performed using the estimated age-specific mortality rates to forecast life expectancy. RESULTS: Results indicated that MSDP elevated the risk of all-cause mortality (HR = 1.12, 95% CI: 1.09-1.15) and mortality due to neoplasms (HR = 1.10, 95% CI: 1.06-1.12), circulatory (HR = 1.13, 95% CI: 1.06-1.19), respiratory (HR = 1.27, 95% CI: 1.16-1.40) and digestive system diseases (HR = 1.22, 95% CI: 1.08-1.38). Notably, both multiplicative and additive interactions were observed between maternal and personal smoking, with Relative Excess Risk due to Interaction (RERI) values for mortality from all causes, neoplasms, circulatory, and respiratory diseases being 0.21, 0.22, 0.16, and 0.76, respectively. This study also found a trend towards shorter gained life expectancy when maternal smoking and increasing pack-years of personal smoking were combined. CONCLUSIONS: In this cohort study of UK Biobank, MSDP was associated with an increased risk of all-cause mortality and reduced life expectancy, suggesting that quitting smoking during pregnancy might have health and longevity benefits for both generations.


Assuntos
Expectativa de Vida , Neoplasias , Feminino , Gravidez , Humanos , Causas de Morte , Estudos de Coortes , Estudos Prospectivos , Fumar/efeitos adversos , Fatores de Risco
7.
Chemosphere ; 355: 141776, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38522667

RESUMO

The efficient removal of phosphate from water environments was extremely significant to control eutrophication of water bodies and prevent further deterioration of water quality. In this study, oxygen vacancy-rich magnesium oxide (OV-MgO) microspheres were synthesized by a simple solvothermal method coupling high-temperature calcination. The effects of adsorbent dosage, contact time, initial pH and coexisting components on phosphate adsorption performance were examined. The physicochemical properties of OV-MgO microspheres and the phosphate removal mechanisms were analyzed by various characterization techniques. The maximum adsorption capacity predicted by the Sips isotherm model was 379.7 mg P/g for OV-MgO microspheres. The phosphate adsorption in this study had a fast adsorption kinetics and a high selectivity. OV-MgO microspheres had a good acid resistance for phosphate adsorption, but their adsorption capacity decreased under alkaline conditions. The electrostatic attraction, ligand exchange, surface precipitation, inner-sphere surface complexation and oxygen vacancy capture were mainly responsible for efficient removal of phosphate from aqueous solutions. This study probably promoted the development of oxygen vacancy-rich metal (hydr)oxides with potential application prospects.

8.
Environ Res ; 251(Pt 1): 118602, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38431072

RESUMO

Short-chain chlorinated paraffins (SCCPs), a class of persistent organic pollutants, have been found to cause diverse organ and systemic toxicity. However, little is known about their neurotoxic effects. In this study, we exposed BV2, a mouse microglia cell line, to environmentally relevant concentration of SCCPs (1 µg/L, 10 µg/L, 100 µg/L) for 24 h to investigate their impacts on the nervous system. Our observations revealed that SCCPs induced the activation of BV2 microglia, as indicated by altered morphology, stimulated cell proliferation, enhanced phagocytic and migratory capabilities. Analysis at the mRNA level confirmed the activation status, with the downregulation of TMEM119 and Tgfbr1, and upregulation of Iba1 and CD11b. The upregulated expression of genes such as cenpe, mki67, Axl, APOE and LPL also validated alterations in cell functions. Moreover, BV2 microglia presented an M2 alternative phenotype upon SCCPs exposure, substantiated by the reduction of NF-κB, TNF-α, IL-1ß, and the elevation of TGF-ß. Additionally, SCCPs caused lipid metabolic changes in BV2 microglia, characterized by the upregulations of long-chain fatty acids and acylcarnitines, reflecting an enhancement of ß-oxidation. This aligns with our findings of increased ATP production upon SCCPs exposure. Intriguingly, cell activation coincided with elevated levels of omega-3 polyunsaturated fatty acids. Furthermore, activated microglial medium remarkably altered the proliferation and differentiation of mouse neural stem cells. Collectively, exposure to environmentally relevant concentrations of SCCPs resulted in activation and lipid metabolic alterations in BV2 microglia, potentially impacting neurogenesis. These findings provide valuable insights for further research on the neurotoxic effect of SCCPs.

9.
J Hazard Mater ; 470: 134143, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38554507

RESUMO

To address time-consuming and efficiency-limited challenges in conventional zero-valent iron (ZVI, Fe0) reduction or biotransformation for perfluorooctanoic acid (PFOA) treatment, two calcium alginate-embedded amendments (biochar-immobilized PFOA-degrading bacteria (CB) and ZVI (CZ)) were developed to construct microbe-Fe0 high-rate interaction systems. Interaction mechanisms and key metabolic pathways were systematically explored using metagenomics and a multi-process coupling model for PFOA under microbe-Fe0 interaction. Compared to Fe0 (0.0076 day-1) or microbe (0.0172 day-1) systems, the PFOA removal rate (0.0426 day-1) increased by 1.5 to 4.6 folds in the batch microbe-Fe0 interaction system. Moreover, Pseudomonas accelerated the transformation of Fe0 into Fe3+, which profoundly impacted PFOA transport and fate. Model results demonstrated microbe-Fe0 interaction improved retardation effect for PFOA in columns, with decreased dispersivity a (0.48 to 0.20 cm), increased reaction rate λ (0.15 to 0.22 h-1), distribution coefficient Kd (0.22 to 0.46 cm3∙g-1), and fraction f´(52 % to 60 %) of first-order kinetic sorption of PFOA in microbe-Fe0 interaction column system. Moreover, intermediates analysis showed that microbe-Fe0 interaction diversified PFOA reaction pathways. Three key metabolic pathways (ko00362, ko00626, ko00361), eight functional genes, and corresponding enzymes for PFOA degradation were identified. These findings provide insights into microbe-Fe0 "neural network-type" interaction by unveiling biotransformation and mineral transformation mechanisms for efficient PFOA treatment.

10.
J Hazard Mater ; 469: 133920, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38457972

RESUMO

Studies on the role of the gut microbiota in the associations between per- and polyfluoroalkyl substance (PFAS) exposure and adverse neurodevelopment are limited. Umbilical cord serum and faeces samples were collected from children, and the Strengths and Difficulties Questionnaire (SDQ) was conducted. Generalized linear models, linear mixed-effects models, multivariate analysis by linear models and microbiome regression-based kernel association tests were used to evaluate the associations among PFAS exposure, the gut microbiota, and neurobehavioural development. Perfluorohexane sulfonic acid (PFHxS) exposure was associated with increased scores for conduct problems and externalizing problems, as well as altered gut microbiota alpha and beta diversity. PFHxS concentrations were associated with higher relative abundances of Enterococcus spp. but lower relative abundances of several short-chain fatty acid-producing genera (e.g., Ruminococcus gauvreauii group spp.). PFHxS exposure was also associated with increased oxidative phosphorylation. Alpha and beta diversity were found significantly associated with conduct problems and externalizing problems. Ruminococcus gauvreauii group spp. abundance was positively correlated with prosocial behavior scores. Increased alpha diversity played a mediating role in the associations of PFHxS exposure with conduct problems. Our results suggest that the gut microbiota might play an important role in PFAS neurotoxicity, which may have implications for PFAS control.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Microbioma Gastrointestinal , Ácidos Sulfônicos , Criança , Feminino , Gravidez , Humanos , Disbiose/induzido quimicamente , Ruminococcus , Fluorocarbonos/toxicidade , Poluentes Ambientais/toxicidade
11.
Case Rep Oncol ; 17(1): 361-369, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38415271

RESUMO

Introduction: Cadonilimab (AK104) is an innovative human programmed cell death-1 (PD-1)/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody. Compared with the combination therapy of PD-1 and CTLA-4 blockers, less cellular toxicity of cadonilimab was significantly manifested. As one of the characteristic adverse effects of cadonilimab, infusion-related reactions (IRRs) represent fever, chills, rash, decreased blood pressure, and other symptoms. Case Presentation: Here, we documented seven cases of IRRs after the administration of cadonilimab. The symptoms of IRRs were relieved after the discontinuation of cadonilimab and the administration of diphenhydramine, dexamethasone, and cimetidine. Notably, 3 patients were able to tolerate the subsequent cadonilimab therapy under the pretreatment. Conclusion: In this study, we discovered that cadonilimab-related IRRs might be lessened or prevented by administering medication and the proper pretreatment and lowering the infusion rate.

12.
JMIR Public Health Surveill ; 10: e47453, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38315527

RESUMO

BACKGROUND: Cough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19. OBJECTIVE: The aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China. METHODS: In this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023. RESULTS: There were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94). CONCLUSIONS: Cough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.


Assuntos
Asma , COVID-19 , Doença das Coronárias , Diabetes Mellitus , Refluxo Gastroesofágico , Feminino , Humanos , Lactente , Masculino , SARS-CoV-2 , Estudos Transversais , Vacinas contra COVID-19 , COVID-19/complicações , COVID-19/epidemiologia , Tosse/epidemiologia , Fatores de Risco , China/epidemiologia , Asma/complicações , Asma/epidemiologia
13.
J Agric Food Chem ; 72(9): 4765-4776, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38393978

RESUMO

Akkermansia muciniphila is a potential candidate for ulcerative colitis prevention. Considering that it utilizes 2'-fucosyllactose (2'FL) for growth, 2'FL can be used to enrich the abundance of A. muciniphila in feces. However, whether the crosswalk between 2'FL and A. muciniphila can promote the intestinal colonization of A. muciniphila remains unclear. In this study, we explored the effect and the underlying mechanism of 2'FL on the colonization of A. muciniphila in vitro and in vivo as well as its alleviating effect on colitis. Our results revealed that 2'FL can serve as a carbon source of A. muciniphila to support the growth and increase cell-surface hydrophobicity and the expression of the genes coding fibronectin-binding autotransporter adhesin to promote the adhesion to Caco2/HT29 methotrexate (MTX) cells but not of galactooligosaccharides (GOS) and glucose. Moreover, 2'FL could increase the host mucin formation to promote the adhesion of A. muciniphila to Caco2/HT29 MTX cells but not of GOS and glucose. Furthermore, 2'FL could significantly increase the colonization of A. muciniphila in the gut to alleviate colitis in mice. Overall, the interplay between A. muciniphila and 2'FL is expected to provide an advantageous ecological niche for A. muciniphila so as to confer further health benefits against colitis.


Assuntos
Colite Ulcerativa , Trissacarídeos , Animais , Humanos , Camundongos , Akkermansia , Células CACO-2 , Colite Ulcerativa/metabolismo , Glucose/metabolismo
14.
iScience ; 27(2): 108815, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38322991

RESUMO

Hypoxia-induced pulmonary hypertension (HPH) is a fatal cardiovascular disease characterized by an elevation in pulmonary artery pressure, resulting in right ventricular dysfunction and eventual heart failure. Exploring the pathogenesis of HPH is crucial, and small noncoding RNAs (sncRNAs) are gaining recognition as potential regulators of cellular responses to hypoxia. In this study, we conducted a comprehensive analysis of sncRNA profiles in eight tissues of male HPH rats using high-throughput sequencing. Our study unveiled several sncRNAs, with the brain, kidney, and spleen exhibiting the highest abundance of microRNA (miRNA), tRNA-derived small RNA (tDR), and small nucleolar RNA (snoRNA), respectively. Moreover, we identified numerous tissue-specific and hypoxia-responsive sncRNAs, particularly miRNAs and tDRs. Interestingly, we observed arm switching in miRNAs under hypoxic conditions and a significant increase in the abundance of 5' tRNA-halves among the total tDRs during hypoxia. Overall, our study provides a comprehensive characterization of the sncRNA profiles in HPH rats.

15.
Plant Cell ; 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38299434

RESUMO

Proper anther dehiscence is essential for successful pollination and reproduction in angiosperms, and jasmonic acid (JA) is crucial for the process. However, the mechanisms underlying tight regulation of JA biosynthesis during anther development remain largely unknown. Here, we demonstrate that the rice (Oryza sativa L.) ERF-associated amphiphilic repression (EAR) motif-containing protein TCP INTERACTOR CONTAINING EAR MOTIF PROTEIN1 (OsTIE1) tightly regulates JA biosynthesis by repressing TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTORS (TCP) transcription factor OsTCP1/PCF5 during anther development. The loss of OsTIE1 function in Ostie1 mutants causes male sterility. The Ostie1 mutants display inviable pollen, early stamen filament elongation and precocious anther dehiscence. In addition, JA biosynthesis is activated earlier and JA abundance is precociously increased in Ostie1 anthers. OsTIE1 is expressed during anther development, and OsTIE1 is localized in nuclei and has transcriptional repression activity. OsTIE1 directly interacts with OsTCP1, and overexpression of OsTCP1 caused early anther dehiscence resembling that of Ostie1. JA biosynthesis genes including rice LIPOXYGENASE (OsLOX) are regulated by the OsTIE1-OsTCP1 complex. Our findings reveal that the OsTIE1-OsTCP1 module plays a critical role in anther development by finely tuning JA biosynthesis and provide a foundation for the generation of male sterile plants for hybrid seed production.

16.
17.
Eur J Nucl Med Mol Imaging ; 51(4): 978-990, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38049658

RESUMO

PURPOSE: A same-day PET imaging agent capable of measuring PD-L1 status in tumors is an important tool for optimizing PD-1 and PD-L1 treatments. Herein we describe the discovery and evaluation of a novel, fluorine-18 labeled macrocyclic peptide-based PET ligand for imaging PD-L1. METHODS: [18F]BMS-986229 was synthesized via copper mediated click-chemistry to yield a PD-L1 PET ligand with picomolar affinity and was tested as an in-vivo tool for assessing PD-L1 expression. RESULTS: Autoradiography showed an 8:1 binding ratio in L2987 (PD-L1 (+)) vs. HT-29 (PD-L1 (-)) tumor tissues, with >90% specific binding. Specific radioligand binding (>90%) was observed in human non-small-cell lung cancer (NSCLC) and cynomolgus monkey spleen tissues. Images of PD-L1 (+) tissues in primates were characterized by high signal-to-noise, with low background signal in non-expressing tissues. PET imaging enabled clear visualization of PD-L1 expression in a murine model in vivo, with 5-fold higher uptake in L2987 (PD-L1 (+)) than in control HT-29 (PD-L1 (-)) tumors. Moreover, this imaging agent was used to measure target engagement of PD-L1 inhibitors (peptide or mAb), in PD-L1 (+) tumors as high as 97%. CONCLUSION: A novel 18F-labeled macrocyclic peptide radioligand was developed for PET imaging of PD-L1 expressing tissues that demonstrated several advantages within a nonhuman primate model when compared directly to adnectin- or mAb-based ligands. Clinical studies are currently evaluating [18F]BMS-986229 to measure PD-L1 expression in tumors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Domínio de Fibronectina Tipo III , Radioisótopos de Flúor , Neoplasias Pulmonares , Proteínas Recombinantes , Humanos , Camundongos , Animais , Antígeno B7-H1/metabolismo , Ligantes , Macaca fascicularis/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Peptídeos/química
18.
Mol Imaging Biol ; 26(2): 301-309, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38123744

RESUMO

PURPOSE: In cancer immunotherapy, the blockade of the interaction between programmed death-1 and its ligand (PD-1:PD-L1) has proven to be one of the most promising strategies. However, as mechanisms of resistance to PD-1/PD-L1 inhibition include variability in tumor cell PD-L1 expression in addition to standard tumor biopsy PD-L1 immunohistochemistry (IHC), a comprehensive and quantitative approach for measuring PD-L1 expression is required. Herein, we report the development and characterization of an 18F-PD-L1-binding macrocyclic peptide as a PET tracer for the comprehensive evaluation of tumor PD-L1 expression in cancer patients. PROCEDURES: 18F-BMS-986229 was characterized for PD-L1 expression assessment by autoradiography or PET imaging. 18F-BMS-986229 was utilized to evaluate tumor PD-L1 target engagement in competition with a macrocyclic peptide inhibitor of PD-L1 (BMS-986189) over a range of doses using PET imaging. A whole-body radiation dosimetry study of 18F-BMS-986229 in healthy non-human primates (NHPs) was performed. RESULTS: In vitro autoradiography showed an 8:1 binding ratio in L2987(PD-L1 +) vs. HT-29 (PD-L1-) tumors, more than 90% of which could be blocked with 1 nM of BMS-986189. Ex vivo autoradiography showed that 18F-BMS-986229 detection was penetrant over a series of sections spanning the entire L2987 tumor. In vivo PET imaging in mice demonstrated a 5:1 tracer uptake ratio (at 90-100 min after tracer administration) in L2987 vs. HT-29 tumors and demonstrated 83%-93% specific binding of BMS-986189 within those dose ranges. In a healthy NHP dosimetry study, the resultant whole-body effective dose was 0.025 mSv/MBq. CONCLUSION: 18F-BMS-986229 has been preclinically characterized and exhibits high target specificity, low background uptake, and a short blood half-life supportive of same day imaging in the clinic. As the PET tracer, 18F-BMS-986229 shows promise in the quantification of PD-L1 expression, and its use in monitoring longitudinal changes in patients may provide insights into PD-1:PD-L1 immuno-therapy treatment outcomes.


Assuntos
Antígeno B7-H1 , Neoplasias , Humanos , Animais , Camundongos , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1 , Tomografia por Emissão de Pósitrons/métodos , Radiometria , Peptídeos
19.
Langmuir ; 40(1): 827-836, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38150270

RESUMO

Heterogeneous Fenton-like catalysis is a widely used method for the degradation of organic pollutants. However, it still has some limitations such as low activity in the neutral condition, low conversion rates of metals with different valence states, and potential secondary metal pollution. In this study, a Fenton-like nanocatalyst was first created by generating ultrasmall copper nanoclusters (Cu NCs) on the surface of hydroxyapatite (HAp) through a process of doping followed by modification. This resulted in the formation of a composite nanocatalyst known as Cu NCs/HAp. With the help of hydrogen peroxide (H2O2), Cu NCs/HAp exhibits an outstanding Fenton-like catalytic performance by efficiently degrading organic dyes such as methylene blue under mild neutral conditions. The removal rate can reach over 83% within just 30 min, demonstrating ideal catalytic universality and stability. The improved Fenton-like catalytic performance of Cu NCs/HAp can be ascribed to the synergistic effect of the multivalent Cu species through two simultaneous reaction pathways. During route I, the embedded Cu NCs with a core-shell Cu0/Cu+ structure can undergo sequential oxidation to form Cu2+, which continuously activates H2O2 to generate hydroxyl radicals (•OH) and singlet oxygen (1O2). In route II, Cu2+ produced from route I and initially adsorbed on the surface of HAp can be reduced by H2O2, thus regenerating Cu+ species for route I and achieving a closed-loop reaction. This work has confirmed that Cu NCs loaded on HAp may be an alternative Fenton-like catalyst for degradation of organic pollutants and environmental remediation, opening up new avenues for potential applications of other Cu NCs in future water pollution control.

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