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1.
Molecules ; 28(4)2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36838884

RESUMEN

Fluoride ion (F-) is one of the most hazardous elements in potable water. Over intake of F- can give rise to dental fluorosis, kidney failure, or DNA damage. As a result, developing affordable, equipment-free and credible approaches for F- detection is an important task. In this work, a new three dimensional rare earth cluster-based metal-organic framework assembled from lanthanide Y(III) ion, and a linear multifunctional ligand 3-nitro-4,4'-biphenyldicarboxylic acid, formulated as {[Y(µ3-OH)]4[Y(µ3-OH)(µ2-H2O)0.25(H2O)0.5]4[µ4-nba]8}n (1), where H2nba = 3-nitro-4,4'-biphenyldicarboxylic acid, has been hydrothermally synthesized and characterized through infrared spectroscopy (IR), elemental and thermal analysis (EA), power X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SCXRD) analyses. X-ray diffraction structural analysis revealed that 1 crystallizes in tetragonal system with P4¯21m space group, and features a 3D framework with 1D square 18.07(3)2 Å2 channels running along the [0,0,1] or c-axis direction. The structure of 1 is built up of unusual eight-membered rings formed by two types of {Y4O4} clusters connected to each other via 12 µ4-nba2- and 4 µ3-OH- ligands. Three crystallographic independent Y3+ ions display two coordinated configurations with a seven-coordinated distorted monocapped trigonal-prism (YO7) and an eight-coordinated approximately bicapped trigonal-prism (YO8). 1 is further stabilized through O-H⋯O, O-H⋯N, C-H⋯O, and π⋯π interactions. Topologically, MOF 1 can be simplified as a 12-connected 2-nodal Au4Ho topology with a Schläfli symbol {420·628·818}{43}4 or a 6-connected uninodal pcu topology with a Schläfli symbol {412·63}. The fluorescent sensing application of 1 was investigated to cations and anions in H2O. 1 exhibits good luminescence probing turn-on recognition ability toward F- and with a limit detection concentration of F- down to 14.2 µM in aqueous solution (Kec = 11403 M-1, R2 = 0.99289, σ = 0.0539). The findings here provide a feasible detection platform of LnMOFs for highly sensitive discrimination of F- in aqueous media.


Asunto(s)
Luminiscencia , Estructuras Metalorgánicas , Compuestos de Bifenilo , Cristalografía por Rayos X
2.
J Transl Med ; 20(1): 288, 2022 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-35761379

RESUMEN

BACKGROUND: Chemoresistance serves as a huge obstacle for acute myeloid leukemia (AML) patients. To counteract the chemoresistance in AML cells, we discussed the role of maternally expressed gene 3 (MEG3) in arabinocytosine (AraC) chemoresistance in AML cells. METHODS: MEG3, microRNA (miR)-493-5p, methyltransferase-like 3 (METTL3) and MYC expression in AML cells was determined and then their interactions were also analyzed. Then, the viability and apoptosis of AML cells were determined through loss- and gain- function assay. The level of m6A modification in AML cells was examined. AML mouse models were also established to validate the potential roles of MEG3. RESULTS: MEG3 and miR-493-5p were downregulated in AML cells, and they were lower in resistant cells than in parental cells. MEG3 led to elevated expression of miR-493-5p which targeted METTL3. METTL3 increased expression of MYC by promoting its m6A levels. Overexpression of MEG3 and miR-493-5p or knockdown of METTL3 inhibited HL-60 and Molm13 cell proliferation and promoted their apoptosis. Overexpressed MEG3 induced heightened sensitivity of AML cells to AraC. However, the suppression of miR-493-5p reversed the effects of overexpressed MEG3 on AML cells. CONCLUSIONS: Collectively, MEG3 could upregulate miR-493-5p expression and suppress the METTL3/MYC axis through MYC m6A methylation, by which MEG3 promoted the chemosensitivity of AML cells.


Asunto(s)
Leucemia Mieloide Aguda , MicroARNs , ARN Largo no Codificante , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Resistencia a Antineoplásicos/genética , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Metiltransferasas/genética , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
3.
Fungal Genet Biol ; 157: 103632, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34710583

RESUMEN

Autophagy plays vital roles in the interaction between the necrotrophic fungal pathogen Sclerotinia sclerotiorum and its hosts. However, so far, only little is known about the impacts of autophagy machinery in S. sclerotiorum per se on the fungal morphogenesis and pathogenesis. Here, through functional genomic approaches, we showed that SsATG8, one of the core components of the autophagy machinery, and its interactor SsNBR1, an autophagy cargo receptor, are important for vegetative growth, sclerotial formation, oxalic acid (OA) production, compound appressoria development, and virulence of S. sclerotiorum. Complementation assays with chimeric fusion constructs revealed that both LDS [AIM (ATG8 interacting motif) / LIR (LC3-interacting region) docking site] and UDS [UIM (ubiquitin-interacting motif) docking site] sites of the SsATG8 are required for its functions in autophagy and pathogenesis. Importantly, ΔSsatg8 and ΔSsnbr1 mutants showed enhanced sensitivity to the exogenous treatment with the proteasome inhibitors bortezomib and carfilzomib, and ΔSsnbr1 mutant had decreased expression of SsATG8 under the proteasomal stress conditions, suggesting that a cross-talk exists between ubiquitin-proteasome and selective autophagy pathways, which enables downstream protein degradation to proceed properly during diverse biological processes. Collectively, our data indicate that SsATG8- and SsNBR1-mediated autophagy is crucial for S. sclerotiorum development, proteasomal stress response and virulence.


Asunto(s)
Fenómenos Biológicos , Complejo de la Endopetidasa Proteasomal , Ascomicetos , Autofagia/genética , Complejo de la Endopetidasa Proteasomal/genética , Virulencia/genética
4.
Mol Plant Microbe Interact ; 33(9): 1095-1097, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32420795

RESUMEN

Olive leaf scab, also known as peacock spot disease, caused by Venturia oleaginea (syn. Spilocaea oleaginea and Fusicladium oleagineum) is the most widespread and economically important fungal disease attacking olive in production countries. Here, we report the first highly contiguous whole-genome sequence (46.08 Mb) of one isolate, YUN35, of V. oleaginea. The described genome sequence and annotation resource will be useful to study the fungal biology, pathogen-host interaction, characterization of genes of interest, and population genetic diversity.


Asunto(s)
Ascomicetos , Genoma Fúngico , Olea/microbiología , Enfermedades de las Plantas/microbiología , Ascomicetos/genética
5.
Environ Microbiol ; 22(12): 4953-4973, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32410295

RESUMEN

Most secretory proteins are folded and modified in the endoplasmic reticulum (ER); however, protein folding is error-prone, resulting in toxic protein aggregation and cause ER stress. Irreversibly misfolded proteins are subjected to ER-associated degradation (ERAD), modified by ubiquitination, and degraded by the 26S proteasome. The yeast ERAD ubiquitin ligase Hrd1p and multispanning membrane protein Der1p are involved in ubiquitination and transportation of the folding-defective proteins. Here, we performed functional characterization of MoHrd1 and MoDer1 and revealed that both of them are localized to the ER and are pivotal for ERAD substrate degradation and the ER stress response. MoHrd1 and MoDer1 are involved in hyphal growth, asexual reproduction, infection-related morphogenesis, protein secretion and pathogenicity of M. oryzae. Importantly, MoHrd1 and MoDer1 mediated conidial autophagic cell death and subsequent septin ring assembly at the appressorium pore, leading to abnormal appressorium development and loss of pathogenicity. In addition, deletion of MoHrd1 and MoDer1 activated the basal unfolded protein response (UPR) and autophagy, suggesting that crosstalk between ERAD and two other closely related mechanisms in ER quality control system (UPR and autophagy) governs the ER stress response. Our study indicates the importance of ERAD function in fungal development and pathogenesis of M. oryzae.


Asunto(s)
Ascomicetos/metabolismo , Degradación Asociada con el Retículo Endoplásmico/fisiología , Retículo Endoplásmico/metabolismo , Proteínas de la Membrana/metabolismo , Pliegue de Proteína , Ubiquitina-Proteína Ligasas/metabolismo , Ascomicetos/patogenicidad , Autofagia/genética , Proteínas de la Membrana/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Transporte de Proteínas/fisiología , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación/fisiología , Respuesta de Proteína Desplegada/genética , Virulencia
6.
J Nanosci Nanotechnol ; 18(7): 4852-4857, 2018 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-29442665

RESUMEN

Immobilization of glycerol dehydrogenase (GDH) from Serratia marcescens H30 onto epoxy functional magnetic nanoparticles by covalent attachment was carried out. The optimal immobilization conditions were obtained as follows: enzyme/support 6.08 mg/g, temperature 25 °C, pH 7.0 and time 8 h. Under these conditions, a high immobilization yield above 90% was obtained. The characterization of the immobilized GDH indicated that enhanced pH and thermal stability were achieved. Kinetic parameters Km of free and immobilized GDH were determined as 10.35 mM and 15.76 mM, respectively. The immobilized GDH retained about 85% initial activity after ten cycles. These results suggested that GDH immobilized onto magnetic nanoparticles is a simple and efficient way for preparation of stable enzyme. And the immobilized GDH has potential applications in the production of DHA.


Asunto(s)
Enzimas Inmovilizadas , Nanopartículas de Magnetita , Deshidrogenasas del Alcohol de Azúcar/química , Estabilidad de Enzimas , Concentración de Iones de Hidrógeno , Cinética , Deshidrogenasas del Alcohol de Azúcar/análisis , Temperatura
7.
Am J Ther ; 24(1): e20-e29, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-26566148

RESUMEN

Elevated serum levels of high-sensitive C-reactive protein (hs-CRP) and total cholesterol (TC) correlate with atherosclerotic vascular disease and increased frequency of vascular events. In this study, we investigated the effect of atorvastatin treatment on serum hs-CRP and TC levels, and the recurrence rate of atrial fibrillation (AF) in patients. Furthermore, a meta-analysis was performed to confirm the findings in this study. A total of 105 patients with AF were recruited to this study, including 55 patients with AF who were treated with amiodarone and atorvastatin (the treatment group) and 50 patients with AF who were treated with only amiodarone (the control group). Patients were treated for 12 months and followed up regularly for 1 year. Serum hs-CRP and TC levels in patients before and after treatment were recorded, and AF recurrence rate at 3, 6, and 12 months of treatment was obtained. Statistical analyses were performed with R 3.1.0 software and STATA 12.0 software. For patients in both treatment and control groups, serum hs-CRP and TC levels were high before the treatments began (both P < 0.05). However, after 12 months of treatment, serum hs-CRP and TC levels in the treatment group was dramatically reduced compared with the control group (hs-CRP: 3.63 ± 2.14 mg/L vs. 2.75 ± 1.89 mg/L, t = 2.24, P = 0.027; TC: 4.66 ± 1.13 mmol/L vs. 4.20 ± 1.06 mmol/L, t = 2.15, P = 0.034). After 12 months of treatment, the AF recurrence rate in the treatment group was significantly lower than the control group (16.4% vs. 34.0%; χ = 4.37; P = 0.037). In addition, 13 studies were selected for meta-analysis. Pooled results of the meta-analysis showed that serum hs-CRP and TC levels decreased significantly in the treatment group compared with the case group [hs-CRP: SMD = 0.95, 95% confidence interval (CI) = 0.62-1.29, and P < 0.001; TC: SMD = 1.39, 95% CI = 0.65-2.13, and P < 0.001]. Our study presents compelling evidence that atorvastatin is highly effective in reducing serum hs-CRP and TC levels and lowering the recurrence rate of AF.


Asunto(s)
Pueblo Asiatico , Atorvastatina/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Proteína C-Reactiva/metabolismo , Colesterol/metabolismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Anciano , Amiodarona/uso terapéutico , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/metabolismo , China , Quimioterapia Combinada , Femenino , Humanos , Masculino , Metaanálisis como Asunto , Persona de Mediana Edad , Recurrencia , Resultado del Tratamiento
8.
Vet Res ; 46: 44, 2015 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-25928577

RESUMEN

Cases of H9N2 avian influenza virus (AIV) in poultry are increasing throughout many Eurasian countries, and co-infections with other pathogens have resulted in high morbidity and mortality in poultry. Few studies have investigated the genetic factors of virus airborne transmission which determine the scope of this epidemic. In this study, we used specific-pathogen-free chickens housed in isolators to investigate the airborne transmissibility of five recombinant H9N2 AIV rescued by reverse genetic technology. The results show that airborne transmission of A/Chicken/Shandong/01/2008 (SD01) virus was related to the neuraminidase (NA) gene, and four amino acid mutations (D368E, S370L, E313K and G381D) within the head region of the SD01 NA, reduced virus replication in the respiratory tract of chickens, reduced virus NA activity, and resulted in a loss of airborne transmission ability in chickens. Similarly, reverse mutations of these four amino acids in the NA protein of r01/NASS virus, conferred an airborne transmission ability to the recombinant virus. We conclude that these four NA residues may be significant genetic markers for evaluating potential disease outbreak of H9N2 AIV, and propose that immediate attention should be paid to the airborne transmission of this virus.


Asunto(s)
Sustitución de Aminoácidos , Pollos , Subtipo H9N2 del Virus de la Influenza A/fisiología , Gripe Aviar/transmisión , Neuraminidasa/genética , Enfermedades de las Aves de Corral/transmisión , Proteínas Virales/genética , Animales , Subtipo H9N2 del Virus de la Influenza A/genética , Gripe Aviar/virología , Neuraminidasa/metabolismo , Enfermedades de las Aves de Corral/virología , Proteínas Virales/metabolismo
9.
Arch Virol ; 160(5): 1267-77, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25782865

RESUMEN

The worldwide circulation of H9N2 avian influenza virus in poultry, the greater than 2.3 % positive rate for anti-H9 antibodies in poultry-exposed workers, and several reports of human infection indicate that H9N2 virus is a potential threat to human health. Here, we found three mutations that conferred high virulence to H9N2 virus in mice after four passages. The PB2-E627K substitution rapidly appeared at the second passage and played a decisive role in virulence. Polymerase complexes possessing PB2-E627K displayed 16.1-fold higher viral polymerase activity when compared to the wild-type virus, which may account for enhanced virulence of this virus. The other two substitutions (HA-N313D and HA-N496S) enhanced binding to both α2,3-linked and α2,6-linked sialic acid receptors; however, the HA-N313D and N496S substitutions alone decreased the virulence of mouse-adapted virus. Furthermore, this mouse-adapted virus was still not transmissible among guinea pigs by direct contact (0/3 pairs). Our findings show that adaption in mice enhanced the viral polymerase activity and receptor-binding ability, which resulted in a virulent phenotype in mice but not a transmissible phenotype in guinea pigs, indicating that host factors play an important role in adaptive evolution of influenza in new hosts.


Asunto(s)
Adaptación Biológica , Sustitución de Aminoácidos , Subtipo H9N2 del Virus de la Influenza A/aislamiento & purificación , Infecciones por Orthomyxoviridae/virología , ARN Polimerasa Dependiente del ARN/genética , Proteínas Virales/genética , Animales , Femenino , Cobayas , Subtipo H9N2 del Virus de la Influenza A/genética , Subtipo H9N2 del Virus de la Influenza A/crecimiento & desarrollo , Subtipo H9N2 del Virus de la Influenza A/fisiología , Ratones Endogámicos BALB C , Mutación Missense , Infecciones por Orthomyxoviridae/transmisión , ARN Polimerasa Dependiente del ARN/metabolismo , Pase Seriado , Proteínas Virales/metabolismo , Virulencia , Acoplamiento Viral , Replicación Viral
10.
Environ Monit Assess ; 187(4): 161, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25740685

RESUMEN

Eight heavy metals, namely Cu, Zn, Fe, Mn, Cd, Ni, Pb, and As in the muscles of nine fish species collected from Nansi Lake, China. were determined, and the potential health risks to local residents via consumption of the fishes were estimated. The results of two-way ANOVA that showed the concentrations of heavy metals in the investigated fish samples were influenced significantly by fish species and sampling sites. Correlation analysis indicated that sampling sites had significant effects on the levels of correlation coefficients among different heavy metal concentrations. Interestingly, although none of the hazard quotient (HQ) values of any individual element was greater than 1 for the investigated exposure population through fish consumption, the hazard index (HI) values were more than 1 for local fishermen, suggesting that local fishermen may be experiencing some adverse health effects. Among the investigated nine fish species, Cyprinus carpio had the highest HQ and HI. As, Pb, and Cd were the most concerning heavy metals in the investigated fish samples due to their higher relative contributions to the HI values.


Asunto(s)
Monitoreo del Ambiente , Peces/metabolismo , Metales Pesados/metabolismo , Contaminantes Químicos del Agua/metabolismo , Animales , China , Contaminación de Alimentos/análisis , Contaminación de Alimentos/estadística & datos numéricos , Lagos/química , Músculos/química , Medición de Riesgo , Alimentos Marinos/análisis
11.
Med Microbiol Immunol ; 203(2): 109-14, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24327325

RESUMEN

The circulation of H9N2 viruses throughout the world, along with their expanded host range, poses a potential health risk to the public, but the host responses to H9N2 virus in mammals were little known. To obtain insight into the host immune responses to the avian H9N2 virus, the expressions of both cytokines and chemokines in the lungs of infected mice were examined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. We found that interferon gamma (IFN-γ) was the dominant antiviral component, and IFN-γ-induced protein 10 kDa, interleukin 6, chemokine (C-C motif) ligand 5 and macrophage inflammatory protein-1 alpha all played a role in pro-inflammatory responses to H9N2 viruses. In conclusion, this research can make us further understand the infection characteristics of H9N2 virus in mammalian host by providing the data on mice lung immune responses to the avian H9N2 virus.


Asunto(s)
Subtipo H9N2 del Virus de la Influenza A/inmunología , Pulmón/inmunología , Pulmón/virología , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Animales , Quimiocina CCL5/inmunología , Femenino , Interferón gamma/inmunología , Interleucina-6/inmunología , Proteínas Inflamatorias de Macrófagos/inmunología , Ratones , Ratones Endogámicos BALB C
12.
Environ Monit Assess ; 186(10): 6039-46, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24859926

RESUMEN

The concentrations of seven heavy metals (HMs) in jujube samples collected from Hetian region (HTR), Hami region (HMR), Erkesu region (ESR), Bayikuleng region (BLR), and Turpan region (TUR) were determined by inductively coupled mass spectrometry (ICP-MS). The accuracy and precision of the analytical method were confirmed by the certified reference material (GBW 07605). In general, the concentration of iron was higher than those of the other six metals in the investigated jujube samples. The Hazard Quotient (HQ) and Hazard Index (HI) were calculated to evaluate the noncarcinogenic health risk from individual metal and combined metals due to the dietary intakes via consumption of jujube. Both HQ and HI levels were far below 1, suggesting no noncarcinogenic risks for Xinjiang adults under the current consumption rates of the jujubes. Among the jujubes from five different regions, BLR jujube had the highest HQ and HI. Fe and As were the most concerning HMs in the investigated jujube samples due to their higher relative contributions to HIs.


Asunto(s)
Contaminantes Ambientales/análisis , Contaminación de Alimentos/estadística & datos numéricos , Metales Pesados/análisis , Ziziphus/química , Adulto , China , Monitoreo del Ambiente/métodos , Contaminación de Alimentos/análisis , Frutas/química , Humanos , Medición de Riesgo
13.
Front Plant Sci ; 15: 1360024, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38745922

RESUMEN

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a crucial enzyme in glycolysis, an essential metabolic pathway for carbohydrate metabolism across all living organisms. Recent research indicates that phosphorylating GAPDH exhibits various moonlighting functions, contributing to plant growth and development, autophagy, drought tolerance, salt tolerance, and bacterial/viral diseases resistance. However, in rapeseed (Brassica napus), the role of GAPDHs in plant immune responses to fungal pathogens remains unexplored. In this study, 28 genes encoding GAPDH proteins were revealed in B. napus and classified into three distinct subclasses based on their protein structural and phylogenetic relationships. Whole-genome duplication plays a major role in the evolution of BnaGAPDHs. Synteny analyses revealed orthologous relationships, identifying 23, 26, and 26 BnaGAPDH genes with counterparts in Arabidopsis, Brassica rapa, and Brassica oleracea, respectively. The promoter regions of 12 BnaGAPDHs uncovered a spectrum of responsive elements to biotic and abiotic stresses, indicating their crucial role in plant stress resistance. Transcriptome analysis characterized the expression profiles of different BnaGAPDH genes during Sclerotinia sclerotiorum infection and hormonal treatment. Notably, BnaGAPDH17, BnaGAPDH20, BnaGAPDH21, and BnaGAPDH22 exhibited sensitivity to S. sclerotiorum infection, oxalic acid, hormone signals. Intriguingly, under standard physiological conditions, BnaGAPDH17, BnaGAPDH20, and BnaGAPDH22 are primarily localized in the cytoplasm and plasma membrane, with BnaGAPDH21 also detectable in the nucleus. Furthermore, the nuclear translocation of BnaGAPDH20 was observed under H2O2 treatment and S. sclerotiorum infection. These findings might provide a theoretical foundation for elucidating the functions of phosphorylating GAPDH.

14.
EClinicalMedicine ; 68: 102415, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38235421

RESUMEN

Background: Although the antibody-drug conjugates (ADCs) have significantly improved the survival outcomes of patients with human epidermal receptor 2 (HER2)-expressing gastric or gastroesophageal junction (G/GEJ) cancer, the efficacy of ADC used as a single agent is limited. Therefore, it is necessary to investigate effective and safe combination regimens. Preclinical data indicated a synergetic antitumour effect of RC48 and programmed cell death protein 1 (PD-1) inhibitors. We aimed to evaluate the safety and efficacy of RC48 plus toripalimab in patients with HER2-expressing G/GEJ cancer and other solid tumours. Methods: This was a open-label, multicentre, phase 1 trial performed at three hospitals in China. Eligible patients had advanced G/GEJ cancer or other solid tumours with HER2 IHC≥1 or ISH positivity and were refractory to at least one line of treatment, or standard treatment was intolerable or unavailable for these patients. This study followed a "3 + 3" design with predefined RC48 dosages of 2.0 mg/kg and 2.5 mg/kg plus toripalimab 3 mg/kg, once every 2 weeks (q2w). The primary objectives were to evaluate the safety and determine the recommended phase II dose (RP2D), and the secondary objectives included assessing the pharmacokinetics (PK) and preliminary efficacy. This study was registered with ClinicalTrials.gov, NCT04280341. Findings: Between July 13, 2020 and August 30, 2022, 56 patients, including 30 patients with G/GEJ cancer and 26 patients with other solid tumours, were enrolled and received RC48 plus toripalimab (n = 7 for RC48 2.0 mg/kg, toripalimab 3 mg/kg, q2w; n = 49 for RC48 2.5 mg/kg, toripalimab 3 mg/kg, q2w). No dose-limiting toxic effects occurred. The RP2D was declared as RC48 2.5 mg/kg plus toripalimab 3 mg/kg, q2w. The most common grade 3 adverse events were a decreased neutrophil count (n = 13), and a decreased white blood cell count (n = 7). The efficacy assessment was completed for 52 patients. Among patients with G/GEJ cancer (n = 30), the confirmed objective response rate (ORR) was 43% (12/28, 95% CI 25, 63), median progression-free survival (PFS) was 6.2 months (95% CI 4.0, 6.9), median overall survival (OS) was 16.8 months (95% CI 7.2, NE). The ORR of patients with G/GEJ cancer receiving RP2D (n = 24) reached 50% (11/22, 95% CI 28, 72), with median PFS of 5.1 months (95% CI 1.4, 7.3) and median OS of 14.0 months (95% CI 6.3, NE). Among patients with G/GEJ cancer who received RP2D, a clinical benefit was observed in both HER2-positive and low HER2 expressing populations, with an ORR of 56% (5/9, 95% CI 21, 86) vs. 46% (6/13, 95% CI 19, 75), median PFS of 7.8 months (95% CI 0.9, NE) vs. 5.1 months (95% CI 1.2, 6.9), median OS of NE months (95% CI 4.3, NE) vs. 14.0 months (95% CI 5.1, NE), respectively. Antitumour activity was also observed for other solid tumours, including breast cancer (5/13) and endometrial carcinoma (1/1). Interpretation: Our findings suggested that RC48 plus toripalimab had a manageable safety profile and showed encouraging efficacy in pretreated patients with HER2-positive and low HER2-expressing G/GEJ cancer. The findings of our phase 1 clinical trial support further investigation of HER2-targeted ADC plus immunotherapy in HER2-expressing G/GEJ cancer and pancancer treatment in the future. Funding: Beijing Municipal Medical Research Institutes, Beijing Medical Research Institute (Z200015).

15.
Plant Cell Rep ; 32(10): 1589-99, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23749099

RESUMEN

KEY MESSAGE: Based on Arabidopsis microarray, we found 8 WRKY genes were up-regulated with Oxalic acid (OA) challenge, AtWRKY28 and AtWRKY75 overexpression lines showed enhanced resistance to OA and Sclerotinia sclerotiorum. The WRKY transcription factors are involved in various plant physiological processes and most remarkably in coping with diverse biotic and abiotic stresses. Oxalic acid (OA) is an important pathogenicity-determinant of necrotrophic phytopathogenic fungi, such as Sclerotina sclerotiorum (S. sclerotiorum) and Botrytis cinerea (B. cinerea). The identification of differentially expressed genes under OA stress should facilitate our understanding of the pathogenesis mechanism of OA-producing fungi in host plants, and the mechanism of how plants respond to OA and pathogen infection. Based on Arabidopsis oligo microarray, we found 8 WRKY genes that were up-regulated upon OA challenge. The Arabidopsis plants overexpressing AtWRKY28 and AtWRK75 showed enhanced resistance to OA and S. sclerotiorum simultaneously. Furthermore, our results showed that overexpression of AtWRKY28 and AtWRK75 induced oxidative burst in host plants, which suppressed the hyphal growth of S. sclerotiorum, and consequently inhibited fungal infection. Gene expression profiling indicates that both AtWRKY28 and AtWRKY75 are transcriptional regulators of salicylic acid (SA)- and jasmonic acid/ethylene (JA/ET)-dependent defense signaling pathways, AtWRKY28 and AtWRKY75 mainly active JA/ET pathway to defend Arabidopsis against S. sclerotiorum and oxalic acid stress.


Asunto(s)
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Ascomicetos , Proteínas de Unión al ADN/genética , Resistencia a la Enfermedad , Ácido Oxálico/farmacología , Enfermedades de las Plantas/genética , Factores de Transcripción/genética , Arabidopsis/microbiología , Ciclopentanos/metabolismo , Etilenos/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Oxilipinas/metabolismo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/microbiología , Estallido Respiratorio
16.
J Fungi (Basel) ; 9(12)2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38132770

RESUMEN

Salicylic acid plays a crucial role during plant defense to Sclerotinia sclerotiorum. Some bacteria and a few fungi can produce salicylate hydroxylase to degrade SA to suppress plant defense and increase their virulence. But there has been no single salicylate hydroxylase in Sclerotinia sclerotiorum identified until now. In this study, we found that SS1G_02963 (SsShy1), among several predicted salicylate hydroxylases in S. sclerotiorum, was induced approximately 17.6-fold during infection, suggesting its potential role in virulence. SsShy1 could catalyze the conversion of SA to catechol when heterologous expression in E. coli. Moreover, overexpression of SsShy1 in Arabidopsis thaliana decreased the SA concentration and the resistance to S. sclerotiorum, confirming that SsShy1 is a salicylate hydroxylase. Deletion mutants of SsShy1 (∆Ssshy1) showed slower growth, less sclerotia production, more sensitivity to exogenous SA, and lower virulence to Brassica napus. The complemented strain with a functional SsShy1 gene recovered the wild-type phenotype. These results indicate that SsShy1 plays an important role in growth and sclerotia production of S. sclerotiorum, as well as the ability to metabolize SA affects the virulence of S. sclerotiorum.

17.
Plants (Basel) ; 12(16)2023 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-37631176

RESUMEN

Botrytis cinerea is a devastating fungal pathogen that causes severe economic losses in global tomato cultivation. Understanding the molecular mechanisms driving tomatoes' response to this pathogen is crucial for developing effective strategies to counter it. Although the Micro-Tom (MT) cultivar has been used as a model, its stage-specific response to B. cinerea remains poorly understood. In this study, we examined the response of the MT and Ailsa Craig (AC) cultivars to B. cinerea at different time points (12-48 h post-infection (hpi)). Our results indicated that MT exhibited a stronger resistant phenotype at 18-24 hpi but became more susceptible to B. cinerea later (26-48 hpi) compared to AC. Transcriptome analysis revealed differential gene expression between MT at 24 hpi and AC at 22 hpi, with MT showing a greater number of differentially expressed genes (DEGs). Pathway and functional annotation analysis revealed significant differential gene expression in processes related to metabolism, biological regulation, detoxification, photosynthesis, and carbon metabolism, as well as some immune system-related genes. MT demonstrated an increased reliance on Ca2+ pathway-related proteins, such as CNGCs, CDPKs, and CaMCMLs, to resist B. cinerea invasion. B. cinerea infection induced the activation of PTI, ETI, and SA signaling pathways, involving the modulation of various genes such as FLS2, BAK1, CERK1, RPM, SGT1, and EDS1. Furthermore, transcription factors such as WRKY, MYB, NAC, and AUX/IAA families played crucial regulatory roles in tomatoes' defense against B. cinerea. These findings provide valuable insights into the molecular mechanisms underlying tomatoes' defense against B. cinerea and offer potential strategies to enhance plant resistance.

18.
Int J Anal Chem ; 2022: 7306597, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35971426

RESUMEN

In order to understand and improve the degradation rate of formaldehyde, the study on the chemical structure and thermal properties of nano-titanium dioxide resin by free formaldehyde was proposed. In this research, nano-titanium dioxide was prepared by the low temperature hydrolysis method and characterized by using the scanning electron microscope (SEM) and X-ray diffraction (XRD). The degradation behavior of formaldehyde was studied by using the degradation rate of formaldehyde in the container as the evaluation index. The influence of the photocatalytic coating on the degradation rate of formaldehyde under different loading conditions, different temperatures, and different humidity was investigated. The experimental results show that the formaldehyde degradation rate of the photocatalytic coating prepared by loading 5 g nano-TiO2 into a 200 g emulsion system can reach 93% under the conditions of room temperature of 25°C, humidity of 50%, and UV lamp irradiation of 120 min. Conclusion. This study is obviously better than the commercial P25 nano-titanium dioxide degradation effect of formaldehyde.

19.
Dalton Trans ; 51(39): 15022-15030, 2022 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-36112028

RESUMEN

A porphyrin-based conjugated organic polymer (COP) was constructed from 5,10,15,20-tetrakis(4-bromophenyl)porphyrin copper (CuTBPP) and 5,5'-bis-ethynyl-2,2'-bipyridine (BPY) via Sonogashira coupling. Its complex Co/CuTBPP-BPY-COP (with dual metal sites composed of copper porphyrin and a cobalt BPY unit) was prepared by coordination with Co2+. All of the prepared CuTBPP-BPY-COP and Co/CuTBPP-BPY-COP compounds exhibited excellent photocatalytic performance toward CO2 reduction under visible-light irradiation without another sacrificial reagent but only H2O. Co/CuTBPP-BPY-COP (dual metal sites) exhibited better photocatalytic activity than CuTBPP-BPY-COP (a single metal site). Co/CuTBPP-BPY-COP retained a higher photocatalysis capacity for CO2 reduction after 10 consecutive cycles. The total quantity of CO product was 263.2 µmol g-1 after 10 h of irradiation. Theoretical studies indicate that introducing Co metal centers and nitro groups are more favorable for the photoreduction catalysis of CO2 compared with that using CuTBPP-BPY-COP.

20.
Plants (Basel) ; 11(5)2022 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-35270180

RESUMEN

SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are central components that drive membrane fusion events during exocytosis and endocytosis and play important roles in different biological processes of plants. In this study, we identified 237 genes encoding SNARE family proteins in B. napus in silico at the whole-genome level. Phylogenetic analysis showed that BnaSNAREs could be classified into five groups (Q (a-, b-, c-, bc-) and R) like other plant SNAREs and clustered into twenty-five subclades. The gene structure and protein domain of each subclade were found to be highly conserved. In many subclades, BnaSNAREs are significantly expanded compared with the orthologous genes in Arabidopsis thaliana. BnaSNARE genes are expressed differentially in the leaves and roots of B. napus. RNA-seq data and RT-qPCR proved that some of the BnaSNAREs are involved in the plant response to S. sclerotiorum infection as well as treatments with toxin oxalic acid (OA) (a virulence factor often secreted by S. sclerotiorum) or abscisic acid (ABA), methyl jasmonate (MeJA), and salicylic acid (SA), which individually promote resistance to S. sclerotiorum. Moreover, the interacted proteins of BnaSNAREs contain some defense response-related proteins, which increases the evidence that BnaSNAREs are involved in plant immunity. We also found the co-expression of BnaSYP121/2s, BnaSNAPs, and BnaVAMP722/3s in B. napus due to S. sclerotiorum infection as well as the probable interaction among them.

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