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BACKGROUND: Effective utilization of plant protection UAVs in peanut cultivation management necessitates a comprehensive grasp of how application volume rates and pesticides influence peanut leaf spot and rust control. This study aimed to compare the effects of application volume rates and pesticides on droplet deposition, disease, leaf retention rate and peanut yield. A T20 plant protection unmanned aerial vehicle (UAV) sprayer was used to apply four various pesticide doses. In comparison, a knapsack sprayer was used to spray with an application volume rate of 450 L ha-1. RESULTS: The results showed a significant difference in droplet deposition between the plant protection UAVs and the electric knapsack sprayer. In the pesticide treatment with an application volume rate of 15.0 L ha-1, there was no significant difference in the deposition on the peanut canopy of each pesticide treatment, but there was a significant difference in the deposition on the ground in the treatment with adding vegetable oil adjuvant. The treatment with added vegetable oil additives showed the worst performance. The treatment with an application volume rate of 22.5 L ha-1 showed the best performance, with the leaf spot control effect being only 0.3% lower than that of the electric knapsack sprayer. CONCLUSION: Plant protection UAV spraying is feasible to control peanut diseases. Considering the operational effectiveness of the plant protection UAV and application volume rate, it is recommended to use an application volume rate of 22.5 L ha-1 without adding vegetable oil adjuvants for field operations. © 2024 Society of Chemical Industry.
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Arachis , Enfermedades de las Plantas , Enfermedades de las Plantas/prevención & control , Plaguicidas , Protección de Cultivos/métodosRESUMEN
Background: Standardized assessments of clinical complete response (cCR) to neoadjuvant chemoradiotherapy (nCRT) for rectal cancer have been established, but their utility and accuracy remain unclear. This study aimed to evaluate the clinical diagnostic value of rectal magnetic resonance imaging (MRI) and endorectal ultrasonography (ERUS) for the determination of cCRs after neoadjuvant immunotherapy and to investigate the concordance between cCR and pathological complete response (pCR). Methods: Ninety-four patients with rectal cancer treated with neoadjuvant radiotherapy with or without immunotherapy were included. The sensitivity, specificity, and accuracy of each evaluation method were calculated. Results: Combined MRI and ERUS assessments found cCR in seven of the 94 patients in our cohort. In the non-immunotherapy group, the sensitivity, specificity, and accuracy of MRI for diagnosing cCR were 50.0%, 85.2%, and 77.1%, respectively, whereas those of ERUS were 50.0%, 92.6%, and 82.9%, respectively; those of combined MRI and ERUS were 25.0%, 96.3%, and 87.5%, respectively. In the immunotherapy group, the sensitivity, specificity, and accuracy with which MRI identified CR were 51.7%, 76.7%, and 64.4%, respectively; those of ERUS were 13.8%, 90.0%, and 52.5%, respectively, and those of combined MRI and ERUS were 10.3%, 96.7%, and 54.2%, respectively. We also found that 32 of 37 patients with pCR did not meet the cCR evaluation criteria. Of these pCR patients, 78.4% (29/37) received immunotherapy. In the entire cohort, there were five pCRs among the seven cCRs. Of the four cCRs that occurred in the immunotherapy group, three were pCRs. Conclusions: Rectal MRI and/or ERUS did not provide sufficiently accurate assessments of cCR in patients with rectal cancer receiving neoadjuvant therapy, especially immunotherapy, and cCR did not predict pCR.
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Background: Post-translational modification by Small Ubiquitin-like MOdifier (SUMO) is an important mechanism to regulate protein activity, protein stability, and localization of substrates. Zbtb21 is a zinc finger and BTB (Broad-complex, Tram-track and Bric à brac) domain-containing transcription factor. Bioinformatic prediction suggests several putative SUMOylated sites in Zbtb21 protein. Methods: Two evolutionarily conserved lysine residues in Zbtb21 protein were mutated alone or in combination to disrupt the binding with SUMO molecules. Western blot and co-immunoprecipitation analyses were performed to detect the SUMOylation state of wild type and mutant Zbtb21 proteins, respectively. Luciferase reporter assays were conducted to evaluate their transcription activities. Meanwhile, immunofluorescence staining was carried out to show their sub-nuclear localizations. Finally, co-immunoprecipitation was performed to detect the interaction between Zbtb21 and its partners. Results: Phylogenetically conserved lysines 419 and 845 of zebrafish Zbtb21 protein can be conjugated with SUMO molecules. SUMOylation does not affect the subcellular localization and protein stability of Zbtb21, as well as the interaction with Zbtb14 or Zbtb21. Nevertheless, luciferase reporter assays revealed that Zbtb21 is a dual-function transcription factor which exerts activation or repression effect on different promoters, and SUMOylation can modulate the transcriptional activity of Zbtb21 in regulating downstream target genes. Hence, Zbtb21 is identified as a novel substrate of SUMOylation, which would be important for its function. Conclusions: Zebrafish Zbtb21 protein can be SUMOylated on lysines 419 and 845, which is evolutionary conserved. SUMOylation affects the dual role of Zbtb21 on transcription.
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Sumoilación , Proteínas de Pez Cebra , Pez Cebra , Sumoilación/genética , Animales , Pez Cebra/genética , Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Transcripción Genética/genética , HumanosRESUMEN
The condensation of acetyl-CoA with malonyl-acyl carrier protein (ACP) by ß-ketoacyl-ACP synthase III (KAS III, FabH) and decarboxylation of malonyl-ACP by malonyl-ACP decarboxylase are the two pathways that initiate bacterial fatty acid synthesis (FAS) in Escherichia coli. In addition to these two routes, we report that Pseudomonas putida F1 ß-ketoacyl-ACP synthase I (FabB), in addition to playing a key role in fatty acid elongation, also initiates FAS in vivo. We report that although two P. putida F1 fabH genes (PpfabH1 and PpfabH2) both encode functional KAS III enzymes, neither is essential for growth. PpFabH1 is a canonical KAS III similar to E. coli FabH whereas PpFabH2 catalyzes condensation of malonyl-ACP with short- and medium-chain length acyl-CoAs. Since these two KAS III enzymes are not essential for FAS in P. putida F1, we sought the P. putida initiation enzyme and unexpectedly found that it was FabB, the elongation enzyme of the oxygen-independent unsaturated fatty acid pathway. P. putida FabB decarboxylates malonyl-ACP and condenses the acetyl-ACP product with malonyl-ACP for initiation of FAS. These data show that P. putida FabB, unlike the paradigm E. coli FabB, can catalyze the initiation reaction in FAS.
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3-Oxoacil-(Proteína Transportadora de Acil) Sintasa , Pseudomonas putida , 3-Oxoacil-(Proteína Transportadora de Acil) Sintasa/genética , 3-Oxoacil-(Proteína Transportadora de Acil) Sintasa/metabolismo , Proteína Transportadora de Acilo/metabolismo , Escherichia coli/metabolismo , Elongasas de Ácidos Grasos/genética , Elongasas de Ácidos Grasos/metabolismo , Ácidos Grasos , Glucógeno Sintasa , Pseudomonas putida/genética , Pseudomonas putida/metabolismoRESUMEN
[This corrects the article DOI: 10.3892/etm.2019.7253.].
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Neutrophils are key component of the innate immune system in vertebrates. Diverse transcription factors and cofactors act in a well-coordinated manner to ensure proper neutrophil development. Dysregulation of the transcriptional program triggering neutrophil differentiation is associated with various human hematologic disorders such as neutropenia, neutrophilia, and leukemia. In the current study we show the zinc finger protein Znf687 is a lineage-preferential transcription factor, whose deficiency leads to an impaired neutrophil development in zebrafish. Mechanistically, Znf687 functions as a negative regulator of gfi1aa, a pivotal modulator in terminal granulopoiesis, to regulate neutrophil maturation. Moreover, we found BRD4, an important epigenetic regulator, directly interacts with ZNF687 in neutrophils. Deficiency of brd4 results in similar defective neutrophil development as observed in znf687 mutant zebrafish. Biochemical and genetic analyses further reveal that instead of serving as a canonical transcriptional coactivator, Brd4 directly interacts and bridges Znf687 and Smrt nuclear corepressor on gfi1aa gene's promoter to exert transcription repression. In addition, the ZNF687-BRD4-SMRT-GFI1 transcriptional regulatory network is evolutionary conserved in higher vertebrate. Overall, our work indicates Znf687 and Brd4 are two novel master regulators in promoting terminal granulopoiesis.
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Neutrófilos , Factores de Transcripción , Animales , Proteínas que Contienen Bromodominio , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Neutrófilos/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Pez Cebra/metabolismoRESUMEN
The last step of the initiation phase of fatty acid biosynthesis in most bacteria is catalyzed by the 3-ketoacyl-acyl carrier protein (ACP) synthase III (FabH). Pseudomonas syringae pv. syringae strain B728a encodes two FabH homologs, Psyr_3467 and Psyr_3830, which we designated PssFabH1 and PssFabH2, respectively. Here, we explored the roles of these two 3-ketoacyl-ACP synthase (KAS) III proteins. We found that PssFabH1 is similar to the Escherichia coli FabH in using acetyl-acetyl-coenzyme A (CoA ) as a substrate in vitro, whereas PssFabH2 uses acyl-CoAs (C4-C10) or acyl-ACPs (C6-C10). Mutant analysis showed that neither KAS III protein is essential for the de novo fatty acid synthesis and cell growth. Loss of PssFabH1 reduced the production of an acyl homoserine lactone (AHL) quorum-sensing signal, and this production was partially restored by overexpressing FabH homologs from other bacteria. AHL production was also restored by inhibiting fatty acid elongation and providing exogenous butyric acid. Deletion of PssFabH1 supports the redirection of acyl-ACP toward biosurfactant synthesis, which in turn enhances swarming motility. Our study revealed that PssFabH1 is an atypical KAS III protein that represents a new KAS III clade that functions in providing a critical fatty acid precursor, butyryl-ACP, for AHL synthesis.IMPORTANCEAcyl homoserine lactones (AHLs) are important quorum-sensing compounds in Gram-negative bacteria. Although their formation requires acylated acyl carrier proteins (ACPs), how the acylated intermediate is shunted from cellular fatty acid synthesis to AHL synthesis is not known. Here, we provide in vivo evidence that Pseudomonas syringae strain B728a uses the enzyme PssFabH1 to provide the critical fatty acid precursor butyryl-ACP for AHL synthesis. Loss of PssFabH1 reduces the diversion of butyryl-ACP to AHL, enabling the accumulation of acyl-ACP for synthesis of biosurfactants that contribute to bacterial swarming motility. We report that PssFabH1 and PssFabH2 each encode a 3-ketoacyl-acyl carrier protein synthase (KAS) III in P. syringae B728a. Whereas PssFabH2 is able to function in redirecting intermediates from ß-oxidation to fatty acid synthesis, PssFabH1 is an atypical KAS III protein that represents a new KAS III clade based on its sequence, non-involvement in cell growth, and novel role in AHL synthesis.
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3-Oxoacil-(Proteína Transportadora de Acil) Sintasa , Acil-Butirolactonas , Pseudomonas syringae/genética , Pseudomonas syringae/metabolismo , 3-Oxoacil-(Proteína Transportadora de Acil) Sintasa/genética , 3-Oxoacil-(Proteína Transportadora de Acil) Sintasa/química , 3-Oxoacil-(Proteína Transportadora de Acil) Sintasa/metabolismo , Ácidos Grasos/metabolismo , Bacterias/metabolismo , Escherichia coli/metabolismo , Acetilcoenzima A/metabolismoRESUMEN
PURPOSE: Several studies have demonstrated the effectiveness of anti-angiogenic drugs in combination with immune checkpoint inhibitors (ICIs) in patients with microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC). However, whether combination radiotherapy (RT) can further improve the prognosis of mCRC patients after second-line treatment remains to be explored. METHODS: Retrospective analysis of data from mCRC patients who received anti-angiogenic targeted therapy (TT) and immunotherapy (IT) with or without RT after the failure of standard therapy. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated. RESULTS: A total of 82 patients who received TT + IT were analyzed. For RT group (n = 42) versus NRT group (n = 40), ORR was 21.4% (9/42) versus 5.0% (2/40); DCR was 83.8% (35/42) versus 65.0% (26/40). Compared with NRT group, RT improved PFS (median: 5.0 vs. 3.6 months; p = 0.04) and OS (median: 15.2 vs. 7.2 months; p = 0.01). In addition, in the population receiving RT, the PFS of RT sequential/simultaneous TT + IT was superior to TT + IT sequential RT (median: 7.1 vs. 6.2 vs. 3.5 months, p = 0.004). Multivariate analysis suggested RT was an independent prognostic factor for PFS and OS. No treatment-related deaths were reported. CONCLUSIONS: Compared with TT + IT, RT combined with TT + IT improved survival outcomes in MSS/pMMR mCRC patients, with manageable toxicity. RT sequential/simultaneous TT + IT treatment is expected to be the optimal strategy for MSS/PMMR mCRC.
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Inhibidores de la Angiogénesis , Neoplasias Colorrectales , Inhibidores de Puntos de Control Inmunológico , Humanos , Masculino , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Femenino , Persona de Mediana Edad , Inhibidores de la Angiogénesis/uso terapéutico , Estudios Retrospectivos , Anciano , Adulto , Reparación de la Incompatibilidad de ADN , Inestabilidad de Microsatélites , Anciano de 80 o más Años , Quimioradioterapia/métodos , Quimioradioterapia/efectos adversos , Supervivencia sin ProgresiónRESUMEN
Background: Stenotrophomonas maltophilia is a multidrug-resistant (MDR) opportunistic pathogen with high resistance to most clinically used antimicrobials. The dissemination of MDR S. maltophilia and difficult treatment of its infection in clinical settings are global issues. Methods: To provide more genetic information on S. maltophilia and find a better treatment strategy, we isolated five S. maltophilia, SMYN41-SMYN45, from a Chinese community that were subjected to antibiotic susceptibility testing, biofilm formation assay, and whole-genome sequencing. Whole-genome sequences were compared with other thirty-seven S. maltophilia sequences. Results: The five S. maltophilia strains had similar antibiotic resistance profiles and were resistant to ß-lactams, aminoglycosides, and macrolides. They showed similar antimicrobial resistance (AMR) genes, including various efflux pumps, ß-lactamase resistance genes (blaL1/2), aminoglycoside resistance genes [aac(6'), aph(3'/6)], and macrolide-resistant gene (MacB). Genome sequencing analysis revealed that SMYN41-SMYN45 belonged to sequence type 925 (ST925), ST926, ST926, ST31, and ST928, respectively, and three new STs were identified (ST925, ST926, and ST928). Conclusion: This study provides genetic information by comparing genome sequences of several S. maltophilia isolates from a community of various origins, with the aim of optimizing empirical antibiotic medication and contributing to worldwide efforts to tackle antibiotic resistance.
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Antiinfecciosos , Infecciones por Bacterias Gramnegativas , Stenotrophomonas maltophilia , Humanos , Stenotrophomonas maltophilia/genética , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Farmacorresistencia Microbiana , Genómica , Pruebas de Sensibilidad MicrobianaRESUMEN
The physical properties, free amino acids, and metabolites of Beijing-You chicken (BYC) breast meat aged 90, 120, and 150 days were analyzed to investigate the flavor changes with age. The shear force and intramuscular fat increased from 90 to 120 days significantly. The contents of total free amino acids and essential amino acids decreased from 90 to 120 days significantly. No significant differences were detected between 120 and 150 days. The contents of sweet amino acids, bitter amino acids, and umami amino acids showed no significant differences between different ages. In addition, GC-MS and LC-MS were integrated for metabolite detection in breast meat. A total of 128, 142, and 88 differential metabolites were identified in the comparison groups of 120 d vs. 90 d, 150 d vs. 90 d, and 150 d vs. 120 d. Amino acids and lipids were the main differential metabolites. The pathway analysis showed that arginine biosynthesis, histidine metabolism, purine metabolism, and cysteine and methionine metabolism were the main pathways involved in flavor formation during BYC development. It was also found that the metabolites associated with flavor, such as methionine, cysteine, glucose, anserine, arachidonic acid, and glycerol 1-phosphate, were significantly affected by age.
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BACKGROUND: Circulating cell-free DNA (cfDNA) is a pool of short DNA fragments mainly released from apoptotic hematopoietic cells. Nevertheless, the precise physiological process governing the DNA fragmentation and molecular profile of cfDNA remains obscure. To dissect the DNA fragmentation process, we use a human leukemia cell line HL60 undergoing apoptosis to analyze the size distribution of DNA fragments by shallow whole-genome sequencing (sWGS). Meanwhile, we also scrutinize the size profile of plasma cfDNA in 901 healthy human subjects and 38 dogs, as well as 438 patients with six common cancer types by sWGS. RESULTS: Distinct size distribution profiles were observed in the HL60 cell pellet and supernatant, suggesting fragmentation is a stepwise process. Meanwhile, C-end preference was seen in both intracellular and extracellular cfDNA fragments. Moreover, the cfDNA profiles are characteristic and conserved across mammals. Compared with healthy subjects, distinct cfDNA profiles with a higher proportion of short fragments and lower C-end preference were found in cancer patients. CONCLUSIONS: Our study provides new insight into fragmentomics of circulating cfDNA processing, which will be useful for early diagnosis of cancer and surveillance during cancer progression.
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Ácidos Nucleicos Libres de Células , Neoplasias , Humanos , Animales , Perros , Fragmentación del ADN , ADN , Apoptosis , MamíferosRESUMEN
Anthracnose caused by Colletotrichum scovillei is one of the most destructive diseases of chili worldwide. Florylpicoxamid is a new quinone inside inhibitor (QiI) fungicide, which shows intensively inhibitory activity against C. scovillei. Currently, florylpicoxamid is in the registration process to control chili anthracnose in China. This study investigated the risk of resistance and resistance genetic mechanism of C. scovillei to florylpicoxamid. Baseline sensitivity of 141C. scovillei isolates to florylpicoxamid was established with an average EC50 value of 0.2328 ± 0.0876 µg/mL. A total of seven stable florylpicoxamid-resistant mutants were obtained with resistance factors ranging from 41 to 276. The mutants showed similar or weaker traits in mycelial growth, sporulation, conidial germination and pathogenicity than their parental isolates. Generally, the resistance risk of C. scovillei to florylpicoxamid would be moderate. In addition, there was no cross-resistance between florylpicoxamid and the commercially available fungicides tested. A37V and S207L mutations in the cytochrome b protein were detected in four high-resistance and three moderate-resistance mutants, respectively, of which, S207L is a new mutation. Molecular docking showed that the two mutations conferred different resistance levels to florylpicoxamid. These results provide a new perspective for QiI fungicide-resistance mechanism and may help in the reasonable use of florylpicoxamid against chili anthracnose in the future.
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Fungicidas Industriales , Mutación Puntual , Citocromos b/genética , Simulación del Acoplamiento Molecular , Enfermedades de las Plantas , Fungicidas Industriales/farmacologíaRESUMEN
BACKGROUND: Activation of the NOTCH signaling pathway is associated with tumorigenesis. The aim of this study was to investigate NOTCH pathway gene functions and regulatory mechanisms in ovarian cancer (OC). METHODS: We conducted a bioinformatics analysis of publicly available datasets in order to identify potential NOTCH-related mechanisms, associated genes, biological pathways, and their relation to immune function. RESULTS: Significant differential expression of the NOTCH pathway genes DLL1, DLL3, DLL4, HES1, HEY1, JAG1, NOTCH2, NOTCH3, and NOTCH4 was observed between OC samples and normal controls. Low expression of DLL4 and of NOTCH4 in OC patients was associated with International Federation of Gynecology and Obstetrics (FIGO) stage (p <0.001 and p = 0.036, respectively), while high expression of NOTCH3 was associated with race (p = 0.039) and age (p = 0.044). JAG2 and NOTCH1 expression were significantly associated with progression-free interval (PFI) (p = 0.011 and p = 0.039, respectively). DLL1 (Hazard Ratio (HR): 2.096; 95% CI: 1.522-2.886, p < 0.001) and NOTCH1 (HR: 0.711; 95% CI: 0.514-0.983, p = 0.039) expression were independently associated with PFI in multivariate analysis. DLL1, DLL3, JAG1, JAG2, NOTCH3 and NOTCH4 expression could significantly differentiate OC from non-cancer samples. Genes associated with the NOTCH pathway were mainly enriched in five signaling pathways: the NOTCH signaling pathway, breast cancer, endocrine resistance, Th1 and Th2 cell differentiation, and oxidative phosphorylation. The expression of NOTCH pathway genes was significantly associated with immune cell infiltration. CONCLUSIONS: NOTCH pathway genes appear to play an important role in the progression of OC by regulating immune cells, endocrine resistance, Th1 and Th2 cell differentiation, and oxidative phosphorylation. JAG2 and NOTCH1 are potential biomarkers and therapeutic targets for the treatment of OC.
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Relevancia Clínica , Neoplasias Ováricas , Embarazo , Humanos , Femenino , Transducción de Señal/genética , Neoplasias Ováricas/genética , Proteínas de la Membrana/genética , Péptidos y Proteínas de Señalización IntracelularRESUMEN
T cell leukemia homeobox 2 (TLX2) plays an important role in some tumors. Bioinformatics and experimental validation represent a useful way to explore the mechanisms and functions of TLX2 gene in the cancer disease process from a pan cancer perspective. TLX2 was aberrantly expressed in pan cancer and cell lines and correlated with clinical stage. High TLX2 expression was significantly associated with poor overall survival in COAD, KIRC, OC, and UCS. The greatest frequency of TLX2 alterations in pan cancer was amplification. Alterations of NXF2B, MSLNL, PCGF1, INO80B-WBP1, LBX2-AS1, MRPL53, LBX2, TTC31, WDR54, and WBP1 co-occurred in the TLX2 alteration group. PFS was significantly shorter in the TLX2-altered group (n = 6) compared to the TLX2-unaltered group (n = 400). Methylation levels of TLX2 were high in 17 tumors. TLX2 expression was associated with MSI in seven tumors and TMB in five tumors. TLX2 expression was associated with immune infiltration and immune checkpoint genes. TLX2 may be associated with some pathways and chemoresistance. We constructed a possible competing endogenous RNA (ceRNA) network of LINC01010/miR-146a-5p/TLX2 in OC. TLX2 expression was significantly upregulated in ovarian cancer cell lines compared to ovarian epithelial cell lines. Aberrant expression of TLX2 in pan cancer may promote tumorigenesis and progression through different mechanisms. TLX2 may represent an important therapeutic target for human cancers.
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Neoplasias Ováricas , Humanos , Femenino , Pronóstico , Neoplasias Ováricas/genética , Carcinogénesis , BiomarcadoresRESUMEN
Chicken age contributes to the meat characteristics; however, knowledge regarding the pathways and proteins associated with meat quality and muscle development are still scarce, especially in chicken thigh meat. Hence, the objective of this study was to elucidate the intricate relationship between these traits by liquid chromatography mass spectrometry at three different ages. A total of 341 differential expressed proteins (DEPs) were screened out (fold change ≥ 1.50 or ≤0.67 and p < 0.05) among 45 thigh meat samples (15 samples per age) of Beijing-You chicken (BYC), collected at the age of 150, 300, or 450 days (D150, D300, and D450), respectively. Subsequently, based on the protein interaction network and Markov cluster algorithm (MCL) analyses, 91 DEPs were divided into 26 MCL clusters, which were associated with pathways of lipid transporter activity, nutrient reservoir activity, signaling pathways of PPAR and MAPK, focal adhesion, ECM-receptor interaction, the cell cycle, oocyte meiosis, ribosomes, taurine and hypotaurine metabolism, glutathione metabolism, muscle contraction, calcium signaling, nucleic acid binding, and spliceosomes. Overall, our data suggest that the thigh meat of BYC at D450 presents the most desirable nutritional value in the term of free amino acids (FAAs) and intramuscular fat (IMF), and a series of proteins and pathways associated with meat quality and development were identified. These findings also provide comprehensive insight regarding these traits across a wide age spectrum.
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Pseudomonas syringae (P. syringae) is a highly prevalent Gram-negative pathogen with over 60 pathogenic variants that cause yield losses of up to 80% in various crops. Traditional control methods mainly involve the application of antibiotics to inactivate pathogenic bacteria, but large-scale application of antibiotics has led to the development of bacterial resistance. Gram-negative pathogens including P. syringae commonly use the type III secretion system (T3SS) as a transport channel to deliver effector proteins into host cells, disrupting host defences and facilitating virulence, providing a novel target for antibacterial drug development. In this study, we constructed a high-throughput screening reporter system based on our previous work to screen for imidazole, oxazole and thiazole compounds. The screening indicated that the three compounds (II-14, II-15 and II-24) significantly inhibited hrpW and hrpL gene promoter activity without influencing the growth of P. syringae, and the inhibitory activity was better than that of the positive control sulforaphane (4-methylsulfinylbutyl isothiocyanate, SFN) at 50 µM. Three compounds suppressed the transcript levels of representative T3SS genes to different degrees, suggesting that the compounds may suppress the expression of T3SS by modulating the HrpR/S-HrpL regulatory pathway. Inoculation experiments indicated that all three compounds suppressed the pathogenicity of Pseudomonas syringae pv. tomato DC3000 in tomato and Pseudomonas syringae pv. phaseolicola 1448A in bean to varying degrees. One representative compound, II-15, significantly inhibited the secretion of the Pst DC3000 AvrPto effector protein. These findings provide a theoretical basis for the development of novel P. syringae T3SS inhibitors for application in disease prevention and control.
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Proteínas de Unión al ADN , Sistemas de Secreción Tipo III , Sistemas de Secreción Tipo III/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Pseudomonas syringae , Virulencia , Regulación Bacteriana de la Expresión Génica , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiologíaRESUMEN
The intranasal spray COVID-19 vaccine was made available for the first time in China, it is necessary to understand receivers' satisfaction and experience toward the vaccine to help optimize vaccination service. A self-administered multicenter cross-sectional questionnaire survey was conducted in Beijing, China, in December 2022. The vaccination experience was evaluated through three dimensions: immediate tolerance, smooth progress, and time-saving. Vaccine acceptability was measured by receivers' preference for the intranasal spray over intramuscular injection after vaccination and their recommendation willingness. Stepwise multinomial and binary logistic regression models were applied to investigate factors associated with vaccine acceptability. Among 10,452 participants included in the analysis, 92.6% felt no discomfort during the inoculation, 99.8% thought the vaccination process went well, and 89.4% deemed it a time-saving option. For vaccine acceptability, 5566 (53.3%) participants were willing to recommend the vaccine to others, 534 (5.1%) refused, and 4352 (41.6%) had not decided yet; 6142 (58.8%) participants preferred the intranasal spray, 873 (8.4%) preferred the intramuscular injection, and 3437 (32.9%) had no preferences. The most concerned aspects of the intranasal spray vaccine were vaccine effectiveness and safety. Receivers who perceived higher vaccine effectiveness or safety were more likely to recommend it to others (OR, 95%CI: 4.41, 3.24-6.00; 6.11, 4.52-8.27) or prefer it over intramuscular injection after vaccination (OR, 95%CI: 5.94, 4.62-7.65; 8.50, 6.70-10.78). Receivers showed good acceptability and experience toward the intranasal spray COVID-19 vaccine. Vaccine effectiveness and safety were the most concerned aspects, and corresponding publicity and education efforts may help improve vaccine acceptability.
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COVID-19 , Vacunas contra la Influenza , Orthomyxoviridae , Humanos , Vacunas contra la COVID-19 , Estudios Transversales , Beijing , COVID-19/prevención & control , China , VacunaciónRESUMEN
BACKGROUND: Bacterial wilt induced by Ralstonia solanacearum is regarded as one of the most devastating diseases. However, excessive and repeated use of the same bactericides has resulted in development of bacterial resistance. Targeting bacterial virulence factors, such as type III secretion system (T3SS), without inhibiting bacterial growth is a possible assay to discover new antimicrobial agents. RESULTS: In this work, identifying new T3SS inhibitors, a series of mandelic acid derivatives with 2-mercapto-1,3,4-thiazole moiety was synthesized. One of them, F-24, inhibited the transcription of hrpY gene significantly. The presence of this compound obviously attenuated hypersensitive response (HR) without inhibiting bacterial growth of R. solanacearum. The transcription levels of those typical T3SS genes were reduced to various degrees. The test of the ability of F-24 in protecting plants demonstrated that F-24 protected tomato plants against bacterial wilt without restricting the multiplication of R. solanacearum. The mechanism of this T3SS inhibition is through the PhcR-PhcA-PrhG-HrpB pathway. CONCULSION: The screened F-24 could inhibit R. solanacearum T3SS and showed better inhibitory activity than previously reported inhibitors without affecting the growth of the strain, and F-24 is a compound with good potential in the control of R. solanacearum. © 2023 Society of Chemical Industry.