Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 416
Filtrar
1.
Nat Microbiol ; 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39424982

RESUMEN

Enteroviruses contain multiple serotypes and can cause severe neurological complications. The intricate life cycle of enteroviruses involving dynamic virus-receptor interaction hampers the development of broad therapeutics and vaccines. Here, using function-based screening, we identify a broadly therapeutic antibody h1A6.2 that potently protects mice in lethal models of infection with both enterovirus A71 and coxsackievirus A16 through multiple mechanisms, including inhibition of the virion-SCARB2 interactions and monocyte/macrophage-dependent Fc effector functions. h1A6.2 mitigates inflammation and improves intramuscular mechanics, which are associated with diminished innate immune signalling and preserved tissue repair. Moreover, cryogenic electron microscopy structures delineate an adaptive binding of h1A6.2 to the flexible and dynamic nature of the VP2 EF loop with a binding angle mimicking the SCARB2 receptor. The coordinated binding mode results in efficient binding of h1A6.2 to all viral particle types and facilitates broad neutralization of enterovirus, therefore informing a promising target for the structure-guided design of pan-enterovirus vaccine.

2.
Quant Imaging Med Surg ; 14(10): 7640-7653, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39429567

RESUMEN

Background: Photorefractive intrastromal corneal cross-linking (PiXL) treatment corrects myopia by enhancing localized central corneal biomechanics. However, the dose-effect relationship between the changes in corneal biomechanics and alterations in corneal curvature resulting from this treatment remain unclear. We therefore developed an acoustic radiation force optical coherence elastography (ARF-OCE) technique to investigate the dose-effect relationship in PiXL. Methods: ARF-OCE measurements and corneal topography were performed 3 days before and 1 week after PiXL treatment. Depth-resolved Young's modulus images of the in vivo corneas were obtained based on the phase velocity of the Lamb wave. PiXL treatments with five ultraviolet-A (UVA) energy doses (5.4, 15, 25, 35, and 45 J/cm2) were administered to rabbit corneas in vivo (n=15). Results: The percentage change in Young's modulus (ΔE%) of the cornea increased from 0.26 to 1.71 as the UVA energy dose increased from group I (5.4 J/cm2) to group V (45 J/cm2). Meanwhile, the change in the mean keratometry (ΔKm ) of the cornea increased from 0.40 to 2.10 diopters (D) as the UVA energy dose increased from group I to group IV (35 J/cm2). Furthermore, a statistically significant positive correlation was observed between ΔE% and ΔKm in groups I to IV. Conclusions: With increasing UVA energy dose, the corneal Young's modulus significantly increased. Given the observed correlation, ΔE% holds promise as a new quantitative biomechanical parameter for determining the dose-effect relationship in PiXL treatment. It should be emphasized that there may be an inflection point of ΔE%, at which corneal keratometry ceases to flatten and begins to increase. The ARF-OCE system has demonstrated its efficacy in quantitatively assessing changes in corneal biomechanics in vivo following PiXL treatment. This technique has great potential in facilitating the quantitative determination of the dose-effect relationship in PiXL treatment.

3.
Int Immunopharmacol ; 143(Pt 2): 113397, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39461237

RESUMEN

BACKGROUND: Exosomes derived from primary chondrogenic stem/progenitor cells (CSPCs-EXOs) show promise in cartilage repair due to their immunomodulatory and regenerative properties. However, their specific therapeutic potential in osteoarthritis (OA), especially in modulating immune responses and enhancing chondrocyte function, requires further exploration. This study aims to clarify CSPCs-EXOs' effects on OA by investigating their role in chondrocyte proliferation, migration, inflammation inhibition, and cartilage regeneration. METHODS: A rat model of osteoarthritis was established using monosodium iodoacetate (MIA). CSPCs-EXOs were isolated and characterized before being administered to the OA rats. Comprehensive transcriptomic analysis was conducted to identify differentially expressed genes (DEGs) and signaling pathways influenced by CSPCs-EXOs. Histopathological evaluation of cartilage tissue, immunohistochemistry, and in vitro assays were performed to assess chondrocyte proliferation, migration, inflammation, and intracellular environmental changes. RESULTS: CSPCs-EXOs treatment significantly reduced OA-induced cartilage damage, shown by improved histopathological features, increased chondrocyte proliferation, migration, and enhanced cartilage matrix integrity. CSPCs-EXOs uniquely modulated immune pathways and enhanced cellular repair, setting them apart from traditional treatments. Transcriptomic analysis revealed regulation of immune response, inflammation, oxidative stress, and DNA repair pathways. CSPCs-EXOs downregulated inflammatory cytokines (TNF, IL-17) and upregulated pathways for cellular proliferation, migration, and metabolism. They also altered splicing patterns of DNA repair enzymes, indicating a role in boosting repair mechanisms. CONCLUSIONS: CSPCs-EXOs promote cartilage repair in osteoarthritis by modulating immune responses, inhibiting inflammation, and improving the intracellular environment. These findings emphasize their innovative therapeutic potential and offer key insights into their regenerative mechanisms, positioning CSPCs-EXOs as a promising strategy for OA treatment and a foundation for future clinical applications in cartilage tissue engineering and regenerative medicine.

4.
ACS Nano ; 18(42): 29203-29213, 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39378139

RESUMEN

Long afterglow materials based on carbon dots (CDs) have attracted extensive attention in the field of optics due to their low cost and nontoxic properties. However, the targeted synthesis of specific properties of complex and unknown structures such as CDs remains a daunting challenge. In this study, the powerful nonlinear fitting ability of machine learning was used to explore the afterglow properties of CDs. The XGBoost algorithm demonstrates high prediction accuracy in determining the optimal excitation wavelength, optimal emission wavelength, and afterglow lifetime. Using Bayesian optimization, we screened and synthesized the CDs-based long afterglow materials with the longest lifetime reported so far by a one-step microwave method. By combining quantum chemical calculations with experimental data, we revealed the structure-function relationship between CDs and their precursors through electron-hole analysis. These results show that machine learning can establish nonlinear correlations between precursors and materials with unknown structures, clarify their intrinsic relationships, simplify the material design process, and thus accelerate the development of advanced materials.

6.
Sci Rep ; 14(1): 24317, 2024 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-39414922

RESUMEN

Corticosteroids have always been recommended for severe cases of COVID-19. However, the efficacy of treatment with corticosteroids for COVID-19 during the SARS-CoV-2 omicron outbreak in China has not been reported. Clinical data from 406 patients hospitalized for severe/critical COVID-19 from December 2022 to January 2023 at six hospitals in Chongqing were retrospectively analyzed. The primary outcome was all-cause mortality at 28 days in the groups with and without corticosteroids treatment after propensity score matching (PSM). Secondary outcomes were to compare in-hospital mortality and length of survival time with corticosteroids and those without corticosteroids. This study included 406 patients with severe or critical COVID-19, divided into the corticosteroids group (231, 56.9%) and non-corticosteroids group (175, 43.1%). After PSM, the use of corticosteroids did not reduce all-cause mortality at 28 days (42.5% vs. 39.1%). Univariate analysis showed that corticosteroids were not associated with improved all-cause mortality at 28 days [hazard ratio (HR), 1.019; 95% confidence interval (CI), 0.639-1.623; p = 0.938]. Multivariate analysis showed similar results (HR, 1.047; 95% CI, 0.633-1.732; p = 0.858). Among non-survivors, the survival time was significantly larger in those who received corticosteroids compared with the non-corticosteroid users [median 13 (IQR 6.5-15.5) vs. 6 (4-11.25), p = 0.007]. The use of systemic corticosteroids in severe/critical COVID-19 may provide certain potential survival benefits but does not improve prognosis.


Asunto(s)
Corticoesteroides , Tratamiento Farmacológico de COVID-19 , COVID-19 , Mortalidad Hospitalaria , Hospitalización , SARS-CoV-2 , Humanos , Masculino , Femenino , Estudios Retrospectivos , China/epidemiología , Corticoesteroides/uso terapéutico , Persona de Mediana Edad , Anciano , COVID-19/mortalidad , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/aislamiento & purificación , Puntaje de Propensión , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Adulto
7.
Medicine (Baltimore) ; 103(36): e39451, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39252291

RESUMEN

Previous studies have reported correlations between metabolic factors and abdominal aortic calcification (AAC). However, the causal relationship between blood metabolites and AAC remains to be fully explored. We employed bidirectional two-sample Mendelian randomization (MR) to investigate the potential causal relationships between 486 blood metabolites and AAC. The inverse variance weighted method was primarily utilized for MR analysis, and the MR-Egger, weighted median, and Robust Adjusted Profile Score methods were used for supplementary analysis. Sensitivity analyses were conducted using Radial MR, MR-PRESSO, Cochran Q test, MR-Egger intercept, and leave-one-out analysis to evaluate the heterogeneity and pleiotropy. Furthermore, the Steiger test and linkage disequilibrium score regression were used to assess genetic correlation and directionality. Multivariable MR analysis was performed to evaluate the direct effect of metabolites on AAC. Through rigorous screening, we identified 6 metabolites with presumed causal effects on AAC: 4-methyl-2-oxopentanoate (effect size [ES] 0.46, 95% confidence interval [CI]: 0.10-0.82), erythrose (ES -0.35, 95% CI: -0.59 to -0.11), 10-undecenoate (11:1n1) (ES 0.14, 95% CI: 0.03-0.25), 1-myristoylglycerophosphocholine (ES 0.31, 95% CI: 0.11-0.50), glycerol 2-phosphate (ES 0.20, 95% CI: 0.04-0.37), and the unidentified metabolite X-11469 (ES 0.19, 95% CI: 0.08-0.30). Multivariable MR analysis revealed that genetically predicted erythrose, 10-undecenoate, 1-myristoylglycerophosphocholine, and X-11469 could directly affect AAC independent of other metabolites. Reverse MR analysis revealed an alteration in 12 blood metabolites due to AAC, including caffeine, 1,7-dimethylurate, arachidonic acid, and 1-arachidonoylglycerophosphocholine. This study provides evidence supporting a causal relationship between metabolites and AAC. These findings help elucidate the underlying biological mechanisms of AAC and may offer insights into screening, prevention, and treatment approaches.


Asunto(s)
Aorta Abdominal , Análisis de la Aleatorización Mendeliana , Calcificación Vascular , Humanos , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Calcificación Vascular/sangre , Calcificación Vascular/genética , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/sangre
8.
Discov Oncol ; 15(1): 470, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39331252

RESUMEN

Lung adenocarcinoma (LUAD), a prevalent type of non-small cell lung cancer (NSCLC), was known for its diversity and intricate tumor microenvironment (TME). Comprehending the interaction among human immune-related genes (IRGs) and the TME is vital in the creation of accurate predictive models and specific treatments. We created a risk score based on IRGs and designed a nomogram to predict the prognosis of LUAD accurately. This involved a thorough examination of TME and the infiltration of immune cells in both high-risk and low-risk LUAD groups. Furthermore, the examination of the association between characteristic genes (BIRC5 and BMP5) and immune cells, along with immune checkpoints in the TME, was also conducted. The findings of our research unveiled unique immune profiles and interactions among individuals in the high- and low-risk categories, which contribute to variations in prognosis. LUAD demonstrated significant associations between BIRC5, BMP5, immune cells, and checkpoints, suggesting their involvement in disease advancement and resistance to medication. Furthermore, by correlating our findings with a multidrug database, we identified specific LUAD patient subsets that might benefit from tailored treatments. Our study establishes a groundbreaking prognostic model for LUAD, which not only underscores the importance of the immune context in LUAD but also paves the way for advancing precision medicine strategies in this complex malignancy.

9.
Mar Life Sci Technol ; 6(3): 475-487, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39219683

RESUMEN

Vaccines are one of the most practical means to stop the spreading of Aeromonas veronii in aquaculture. In this study, virulence factor aerolysin mutant NTaer which has lost its hemolytic activity was used as a target antigen. Pichia pastoris constitutive secretory expression NTaer (GS115-NTaer) was used as a potential safe oral vaccine to evaluate its effectiveness on zebrafish immunity. The result shows that vaccination of GS115- NTaer for four weeks did not affect the growth performance of the host, while eliciting an effective immune protective response. Compared with the control group, the GS115-NTaer could significantly up-regulate the relative expression level of the intestinal tight junction protein 1α (TJP1α) gene, and significantly increased the contents of lysozyme (LYZ), complement C3 and C4 in the gut, indicating that the innate immune response of the fish was activated. The relative gene expression levels of macrophage-expressed gene 1 (MPEG1) and T cell receptor (TCR-α) in the gut, and MPEG1, CD4, CD8, TCR-α, GATA3, and T-bet in the spleen were all increased significantly, indicating that the cellular immune response of the fish was activated. Furthermore, the contents of serum IgM and intestinal mucosa IgZ antibodies were significantly increased, which showed that humoral immunity was also activated. Moreover, inoculation with GS115-NTaer significantly changed the structure of gut microbiota. In particular, the relative ratio of (Firmicutes + Fusobacteriota + Bacteroidota)/Proteobacteria was significantly higher than that of the control and GS115 groups. Lastly, the vaccinated fish were challenged with A. veronii, and the relative percent survival of GS115 and the GS115-NTear groups was 14.28% and 33.43%. This improvement of immunity was not only due to the specific immune response but also attributed to the improvement of innate immunity and the gut microbiota which was demonstrated by the germ-free zebrafish model. Collectively, this study provides information on the effectiveness of GS115-NTear as an oral vaccine for the green prevention and control of A. veronii infection in fish aquaculture.

10.
Mater Horiz ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39233605

RESUMEN

Nowadays, thousands of energetic materials have been synthesized, but only a few compounds meet all the high standards of detonation performance comparable to that of the widely used military explosive RDX, thermal stability comparable to that of the most widely used heat-resistant explosive HNS, and impact sensitivity comparable to that of the traditional explosive TNT. Also, as a goal, a novel and unexpected one-step method for constructing the furoxan-bridged energetic compound 3,4-bis(3,8-dinitropyrazolo[5,1-c][1,2,4]triazin-4-amino-7-yl)-1,2,5-oxadiazole 2-oxide (OTF) has been achieved under the conventional TFA/100% HNO3 nitration reaction system from the acetic acid intermediate. In this work, OTF with a high density of 1.90 g cm-3, the highest decomposition temperature of 310 °C (onset) among furoxan-based high explosives to date, superior detonation velocity (DV: 9109 m s-1), and low sensitivity (IS: 25 J) is reported. This work is a giant step forward in the development of advanced high-energy heat-resistant explosives and could improve future possibilities for the design of furoxan-based energetic materials.

11.
Chem Commun (Camb) ; 60(76): 10588-10591, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39235278

RESUMEN

In this paper, three neutral heterocycle-triazolotriazine compounds featuring multiple amino groups and nitro groups were designed and synthesized. Among them, compounds 2 and 6 exhibit high detonation performance (Dv = 8180 m s-1, 8650 m s-1; P = 26.40 GPa, 31.5 GPa), low sensitivities (IS > 40 J, FS > 360 N) and high thermal stabilities (Td = 319 °C, 320 °C) suggesting their potential as alternatives to the traditional thermal-stable explosive HNS (Dv = 7612 m s-1, P = 24.3 GPa, IS = 5 J, FS = 240 N; Td = 318 °C). Meanwhile, compound 4 displays excellent properties (Dv = 8810 m s-1, IS = 15 J, FS = 240 N, Td = 215 °C, ρ = 1.84 g cm-3) which is superior to traditional explosive RDX (Dv = 8795 m s-1, IS = 7.5 J, FS = 120 N, Td = 208 °C, ρ = 1.80 g cm-3) making it a promising candidate as a novel secondary explosive. This research not only advances the field of triazolotriazine-based energetic materials but also explores their potential applications as heat-resistant or high-energy explosives.

12.
Org Lett ; 26(38): 8045-8050, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39291907

RESUMEN

Nitrogen-rich energetic materials have been the focus of a few studies on their isomers. Novel nitrogen-rich energetic compounds TZ, DTZ, and NTZ were synthesized through simple steps. The hydrogen bond networks significantly enhanced their properties (TZ, Td = 290 °C and Dv = 8370 m s-1; DTZ, Td = 282 °C and Dv = 8392 m s-1; and NTZ, Td = 272 °C and Dv = 8762 m s-1), which are superior to their isomers. This realized a balance between the energy and stability of polycyclic tetrazoles, providing insights for high-performance energetic materials.

13.
Org Lett ; 26(39): 8430-8434, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39311441

RESUMEN

Here, azo-fused dinitramino energetic compound 5,5'-dinitramino-8,8'-azo-1,2,5-oxadiazolo[3,4-e][1,2,4]triazolo[4,3-a]pyrazine (4) and its energetic salts 5-7 have been prepared. Azo-fused dinitramino compound 4 exhibits excellent detonation performance (P = 36.13 GPa, and Dv = 9126 m s-1), which is obviously better than that of RDX (Dv = 8796 m s-1, and P = 33.60 GPa). In addition, the thermal stability of carbonyl compound 2 (Td = 325 °C) is similar to that of HNS (Td = 318 °C) and 2 exhibits better energy properties. These properties indicate that azo-dinitramino compound 4 has potential as a new secondary explosive, while carbonyl compound 2 also has potential as a new type of heat-resistant explosive.

14.
Discov Oncol ; 15(1): 348, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134820

RESUMEN

This review explores the intricate roles of metal ions-iron, copper, zinc, and selenium-in glioma pathogenesis and immune evasion. Dysregulated metal ion metabolism significantly contributes to glioma progression by inducing oxidative stress, promoting angiogenesis, and modulating immune cell functions. Iron accumulation enhances oxidative DNA damage, copper activates hypoxia-inducible factors to stimulate angiogenesis, zinc influences cell proliferation and apoptosis, and selenium modulates the tumor microenvironment through its antioxidant properties. These metal ions also facilitate immune escape by upregulating immune checkpoints and secreting immunosuppressive cytokines. Targeting metal ion pathways with therapeutic strategies such as chelating agents and metalloproteinase inhibitors, particularly in combination with conventional treatments like chemotherapy and immunotherapy, shows promise in improving treatment efficacy and overcoming resistance. Future research should leverage advanced bioinformatics and integrative methodologies to deepen the understanding of metal ion-immune interactions, ultimately identifying novel biomarkers and therapeutic targets to enhance glioma management and patient outcomes.

15.
Neuroradiology ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39172166

RESUMEN

OBJECTIVES: To evaluate the (1) successful surgery proportion in patients with clear structural lesions on MRI and single abnormality on 18F-fluorodeoxyglucose positron emission tomography/Magnetic resonance imaging (18F-FDG PET/MRI); (2) predictive value of 18F-FDG PET/MRI for postsurgical outcome in refractory epilepsy patients. METHODS: A retrospective study was conducted on 123 patients diagnosed with refractory epilepsy who underwent presurgical evaluation involving 18F-FDG PET/MRI and were followed for one-year post-surgery. Two neuroradiologists interpreted the PET/MRI images using visual analysis and an asymmetry index based on the standard uptake value. The Engel classification was used to assess surgical outcomes one-year post-surgery. Prognostic factors predicting post-surgical seizure outcomes were explored using univariate and binary logistic regression. RESULTS: Definitely single lesion abnormality was observed in 35.0% (43/123) of the patients on the MRI portion of PET/MRI. The proportion increased to 74.0% (91/123) when 18 F-FDG PET portion was added. About 75% (69/91) of patients displaying a clear-cut lesion on 18 F-FDG PET/MRI were classified as Engel Class I one-year post-surgery. The proportion of Engel Class I patients was not significantly different when comparing MRI-single lesion patients with MRI-negative, PET-single lesion patients one year after surgery (81.4% vs. 70.0%, P = 0.24). Binary logistic regression analysis revealed that the detection of a clear single lesion on 18 F-FDG PET/MRI was a strong positive predictor of a favorable surgical outcome (OR 3.518, 95% CI 1.363-9.077, p = 0.009). CONCLUSION: Single lesion detected on 18 F-FDG PET/MRI is useful to predict good surgical outcome for refractory epilepsy patients; Those patients should be considered as candidates for surgery.

16.
EJNMMI Res ; 14(1): 69, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060564

RESUMEN

BACKGROUND: This study aims to evaluate the effect of various background reference regions on spinal 18F-FET PET imaging, with a focus on distinguishing between spinal tumors and myelitis. To enhance diagnostic accuracy, we investigated the pons and several other spinal cord area as potential references, given the challenges in interpreting spinal PET results. RESULTS: A retrospective analysis was conducted on 30 patients, 15 with cervical myelitis and 15 with cervical tumors, who underwent O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET/MR imaging. The stability of uptake across four regions, including the pons, C2, C2-C7, and T1-T3, was compared. The standardized uptake value ratio (SUVR) was then evaluated using various background regions, and their effectiveness in differentiating between spinal tumors and myelitis was compared. Additionally, we correlated the SUVR values derived from these regions with the Ki-67 proliferation index in tumor patients. The study found no significant difference in SUVmax (U = 110, p = 0.93) and SUVmean (U = 89, p = 0.35) values at lesion sites between myelitis and tumor patients. The pons had the highest average uptake (p < 0.001) compared to the other three regions. However, its coefficient of variation (CV) was significantly lower than that of the C2-C7 (p < 0.0001) and T1-T3 segments (p < 0.05). The SUVRmax values, calculated using the regions of pons, C2-C7 and T1-T3, were found to significantly differentiate between tumors and myelitis (p < 0.05). However, only the pons-based SUVRmean was able to significantly distinguish between the two groups (p < 0.05). Additionally, the pons-based SUVRmax (r = 0.63, p = 0.013) and SUVRmean (r = 0.67, p = 0.007) demonstrated a significant positive correlation with the Ki-67 index. CONCLUSIONS: This study suggests that the pons may be considered a suitable reference region for spinal 18F-FET PET imaging, which can improve the differentiation between spinal tumors and myelitis. The significant correlation between pons-based SUVR values and the Ki-67 index further highlights the potential of this approach in assessing tumor cell proliferation.

17.
RSC Adv ; 14(32): 23225-23231, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39045404

RESUMEN

Copper oxalate is typically synthesized through a precipitation reaction involving copper salts mixed with oxalic acid or oxalate solutions. However, in this study, we were successful in synthesizing well-formed square-like copper oxalate particles under liquid-phase conditions at ambient temperature and pressure using ascorbic acid as the source of the oxalic acid ligand. The addition of cationic surfactant cetyltrimethylammonium bromide (CTAB) caused the morphology of copper oxalate particles to undergo a transition from three-dimensional to two-dimensional. And the inhibition of the assembly of primary copper oxalate nanocrystals along the [001] direction became stronger with the increase of CTAB concentration. The impact of CTAB on the crystallization, growth, and self-assembly processes of primary copper oxalate nanocrystals was analysed using various testing methods. Based on these analyses, the possible mechanism of CTAB-induced synthesis of two-dimensional copper oxalate particles was finally proposed.

18.
J Agric Food Chem ; 72(28): 15474-15486, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38949855

RESUMEN

Corn ear rot and fumonisin caused by Fusarium verticillioides pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity based on naturally occurring lead xanthatin, a series of novel spiropiperidinyl-α-methylene-γ-butyrolactones were rationally designed and synthesized. The in vitro bioassay results indicated that compound 7c showed broad-spectrum in vitro activity with EC50 values falling from 3.51 to 24.10 µg/mL against Rhizoctonia solani and Alternaria solani, which was more active than the positive controls xanthatin and oxathiapiprolin. In addition, compound 7c also showed good antitoxic efficacy against fumonisin with a 48% inhibition rate even at a concentration of 20 µg/mL. Fluorescence quenching and the molecular docking validated both 7c and oxathiapiprolin targeting at FvoshC. RNA sequencing analysis discovered that FUM gene cluster and protein processing in endoplasmic reticulum were downregulated. Our studies have discovered spiropiperidinyl-α-methylene-γ-butyrolactone as a novel FvoshC target-based scaffold for fungicide lead with antitoxin activity.


Asunto(s)
Alternaria , Fungicidas Industriales , Fusarium , Simulación del Acoplamiento Molecular , Rhizoctonia , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Fungicidas Industriales/síntesis química , Alternaria/efectos de los fármacos , Fusarium/efectos de los fármacos , Rhizoctonia/efectos de los fármacos , Relación Estructura-Actividad , Enfermedades de las Plantas/microbiología , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , 4-Butirolactona/farmacología , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Receptores de Esteroides/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/química , Descubrimiento de Drogas , Zea mays/química , Zea mays/microbiología , Estructura Molecular
19.
Dalton Trans ; 53(30): 12641-12648, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39011720

RESUMEN

In recent years, with the development of deep coal mines and petroleum resources and the expansion of the aerospace industry, the pursuit of heat-resistant energetic materials with high thermal stability and high energy has been increasing. Bis(4-nitropyrazole) was employed as an energy bridge to link 1,2,4-triazole, thereby constructing a sophisticated tetracyclic framework in this study. A tetracyclic heat-resistant explosive 5,5'-(4,4'-dinitro-2H,2'H-[3,3'-bipyrazole]-5,5'-diyl)bis(4H-1,2,4-triazole-3,4-diamine) (3) and its derivatives 6-8 with excellent comprehensive performance have been successfully prepared. Particularly noteworthy is that compound 3 has a detonation velocity of 8604 m s-1, which exceeds that of the conventional heat-resistant explosive HNS with a velocity of 7164 m s-1. Furthermore, compound 3 has higher thermal stability (Td = 340 °C) than HNS (Td = 318 °C). In addition, the tetracyclic compound 3 also exhibited extraordinarily low sensitivity (IS > 40 J; FS > 360 N). These unique characteristics make it a potential candidate for novel heat-resistant and insensitive energetic materials.

20.
Sci Rep ; 14(1): 12667, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38831094

RESUMEN

The glutenite reservoir in an exploration area in eastern China is well-developed and holds significant exploration potential as an important oil and gas alternative layer. However, due to the influence of sedimentary characteristics, the glutenite reservoir exhibits strong lateral heterogeneity, significant vertical thickness variations, and low accuracy in reservoir space characterization, which affects the reasonable and effective deployment of development wells. Seismic data contains the three-dimensional spatial characteristics of geological bodies, but how to design a suitable transfer function to extract the nonlinear relationship between seismic data and reservoirs is crucial. At present, the transfer functions are concentrated in low-dimensional or high-dimensional fixed mathematical models, which cannot accurately describe the nonlinear relationship between seismic data and complex reservoirs, resulting in low spatial description accuracy of complex reservoirs. In this regard, this paper first utilizes a fusion method based on probability kernel to fuse seismic attributes such as wave impedance, effective bandwidth, and composite envelope difference. This provide a more intuitive reflection of the distribution characteristics of glutenite reservoirs. Moreover, a hybrid nonlinear transfer function is established to transform the fused attribute cube into an opaque attribute cube. Finally, the illumination model and ray casting method are used to perform voxel imaging of the glutenite reservoirs, brighten the detailed characteristics of reservoir space, and then form a set of methods for ' brightening reservoirs and darkening non-reservoirs ', which improves the spatial engraving accuracy of glutenite reservoirs.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...