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1.
Plant Physiol Biochem ; 210: 108651, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38653098

RESUMEN

Sugar beet (Beta vulgaris L.) is an economically important sugar crop worldwide that is susceptible to sudden waterlogging stress during seedling cultivation, which poses a major threat to sugar beet development and production. Our understanding of the physiological basis of waterlogging tolerance in sugar beet is limited. To investigate the photosynthetic adaptation strategies of sugar beet to waterlogging stress conditions, the tolerant cultivar KUHN1260 (KU) and sensitive cultivar SV1433 (SV) were grown under waterlogging stress, and their photosynthetic function and reactive oxygen species (ROS) metabolism were assessed. Our results showed that waterlogging stress significantly reduced the photosynthetic pigment content, rubisco activity, and expression level of the photosynthetic enzyme genes SvRuBP, SvGAPDH, and SvPRK, gas exchange parameters, and chlorophyll fluorescence parameters, induced damage to the ultrastructure of the chloroplast of the two sugar beet cultivars, inhibited the photosynthetic carbon assimilation capacity of sugar beet leaves, damaged the structural stability of photosystem II (PSII), and disturbed the equilibrium between electrons at the acceptor and donor sides of PSII, which was the result of stomatal and non-stomatal limiting factors. Moreover, the level of ROS, H2O2, and O2▪-, antioxidant enzyme activity, and gene expression levels in the leaves of the two sugar beet cultivars increased over time under waterlogging stress; ROS accumulation was lower and antioxidant enzyme activities and gene expression levels were higher in the waterlogging-tolerant cultivar (KU) than the waterlogging-sensitive cultivar (SV). In sum, these responses in the more tolerant cultivars are associated with their resistance to waterlogging stress. Our findings will aid the breeding of waterlogging-tolerant sugar beet cultivars.


Asunto(s)
Beta vulgaris , Fotosíntesis , Especies Reactivas de Oxígeno , Beta vulgaris/fisiología , Beta vulgaris/metabolismo , Beta vulgaris/genética , Fotosíntesis/fisiología , Especies Reactivas de Oxígeno/metabolismo , Estrés Fisiológico , Hojas de la Planta/metabolismo , Complejo de Proteína del Fotosistema II/metabolismo , Clorofila/metabolismo , Agua/metabolismo
2.
Sci Rep ; 14(1): 9903, 2024 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-38688964

RESUMEN

The edible fungus industry is one of the pillar industries in the Yunnan-Guizhou Plateau, China. The expansion of the planting scale has led to the release of various mushroom residues, such as mushroom feet, and other wastes, which are not treated adequately, resulting in environmental pollution. This study investigated the ability of black soldier fly (Hermetia illucens L.) larvae (BSFL) to degrade mushroom waste. Moreover, this study analyzed changes in the intestinal bacterial community and gene expression of BSFL after feeding on mushroom waste. Under identical feeding conditions, the remaining amount of mushroom waste in Pleurotus ostreatus treatment group was reduced by 18.66%, whereas that in Flammulina velutipes treatment group was increased by 31.08%. Regarding gut microbial diversity, compared with wheat bran-treated control group, Dysgonomonas, Providencia, Enterococcus, Pseudochrobactrum, Actinomyces, Morganella, Ochrobactrum, Raoultella, and Ignatzschineria were the most abundant bacteria in the midgut of BSFL in F. velutipes treatment group. Furthermore, Dysgonomonas, Campylobacter, Providencia, Ignatzschineria, Actinomyces, Enterococcus, Morganella, Raoultella, and Pseudochrobactrum were the most abundant bacteria in the midgut of BSFL in P. ostreatus treatment group. Compared with wheat bran-treated control group, 501 upregulated and 285 downregulated genes were identified in F. velutipes treatment group, whereas 211 upregulated and 43 downregulated genes were identified in P. ostreatus treatment group. Using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we identified 14 differentially expressed genes (DEGs) related to amino sugar and nucleotide sugar metabolism in F. velutipes treatment group, followed by 12 DEGs related to protein digestion and absorption. Moreover, in P. ostreatus treatment group, two DEGs were detected for fructose and mannose metabolism, and two were noted for fatty acid metabolism. These results indicate that feeding on edible mushroom waste can alter the intestinal microbial community structure of BSFL; moreover, the larval intestine can generate a corresponding feedback. These changes contribute to the degradation of edible mushroom waste by BSFL and provide a reference for treating edible mushroom waste using BSFL.


Asunto(s)
Agaricales , Microbioma Gastrointestinal , Larva , Pleurotus , Animales , Larva/microbiología , Pleurotus/metabolismo , Agaricales/metabolismo , Agaricales/genética , Biodegradación Ambiental , Dípteros/microbiología , Dípteros/metabolismo , Flammulina/metabolismo , Flammulina/genética , Bacterias/metabolismo , Bacterias/genética , Bacterias/clasificación
3.
Plant Cell ; 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38552172

RESUMEN

S-acylation is a reversible post-translational modification catalyzed by protein S-acyltransferases (PATs), and acyl protein thioesterases (APTs) mediate de-S-acylation. Although many proteins are S-acylated, how the S-acylation cycle modulates specific biological functions in plants is poorly understood. In this study, we report that the S-acylation cycle of transcription factor MtNAC80 is involved in the Medicago truncatula cold stress response. Under normal conditions, MtNAC80 localized to membranes through MtPAT9-induced S-acylation. In contrast, under cold stress conditions, MtNAC80 translocated to the nucleus through de-S-acylation mediated by thioesterases such as MtAPT1. MtNAC80 functions in the nucleus by directly binding the promoter of the glutathione S-transferase gene MtGSTU1 and promoting its expression, which enables plants to survive under cold stress by removing excess malondialdehyde and H2O2. Our findings reveal an important function of the S-acylation cycle in plants and provide insight into stress response and tolerance mechanisms.

4.
Mol Microbiol ; 121(5): 971-983, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38480679

RESUMEN

Increasing evidence suggests that DNA phosphorothioate (PT) modification serves several purposes in the bacterial host, and some restriction enzymes specifically target PT-DNA. PT-dependent restriction enzymes (PDREs) bind PT-DNA through their DNA sulfur binding domain (SBD) with dissociation constants (KD) of 5 nM~1 µM. Here, we report that SprMcrA, a PDRE, failed to dissociate from PT-DNA after cleavage due to high binding affinity, resulting in low DNA cleavage efficiency. Expression of SBDs in Escherichia coli cells with PT modification induced a drastic loss of cell viability at 25°C when both DNA strands of a PT site were bound, with one SBD on each DNA strand. However, at this temperature, SBD binding to only one PT DNA strand elicited a severe growth lag rather than lethality. This cell growth inhibition phenotype was alleviated by raising the growth temperature. An in vitro assay mimicking DNA replication and RNA transcription demonstrated that the bound SBD hindered the synthesis of new DNA and RNA when using PT-DNA as the template. Our findings suggest that DNA modification-targeting proteins might regulate cellular processes involved in DNA metabolism in addition to being components of restriction-modification systems and epigenetic readers.


Asunto(s)
Replicación del ADN , Proteínas de Escherichia coli , Escherichia coli , Azufre , Escherichia coli/metabolismo , Escherichia coli/genética , Azufre/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , ADN Bacteriano/metabolismo , Enzimas de Restricción del ADN/metabolismo , Unión Proteica , ADN/metabolismo , Sitios de Unión
5.
Curr Res Toxicol ; 6: 100161, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38496008

RESUMEN

Cigarette smoking (CS) causes skeletal muscle dysfunction, leading to sarcopenia and worse prognosis of patients with diverse systemic diseases. Here, we found that CS exposure prevented C2C12 myoblasts proliferation in a dose-dependent manner. Immunoblotting assays verified that CS exposure promoted the expression of cell cycle suppressor protein p21. Furthermore, CS exposure significantly inhibited replication-dependent (RD) histone transcription and caused S phase arrest in the cell cycle during C2C12 proliferation. Mechanistically, CS deregulated the expression levels of Nuclear Protein Ataxia-Telangiectasia Locus (NPAT/p220). Notably, the proteasome inhibitor MG132 was able to reverse the expression of NPAT in myoblasts, implying that the degradation of CS-mediated NPAT is proteasome-dependent. Overexpression of NPAT also rescued the defective proliferation phenotype induced by CS in C2C12 myoblasts. Taken together, we suggest that CS exposure induces NPAT degradation in C2C12 myoblasts and impairs myogenic proliferation through NPAT associated proteasomal-dependent mechanisms. As an application of the proteasome inhibitor MG132 or overexpression of NPAT could reverse the impaired proliferation of myoblasts induced by CS, the recovery of myoblast proliferation may be potential strategies to treat CS-related skeletal muscle dysfunction.

6.
Sci China Life Sci ; 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38523237

RESUMEN

Fucosyltransferase 8 (Fut8) and core fucosylation play critical roles in regulating various biological processes, including immune response, signal transduction, proteasomal degradation, and energy metabolism. However, the function and underlying mechanism of Fut8 and core fucosylation in regulating adult neurogenesis remains unknown. We have shown that Fut8 and core fucosylation display dynamic features during the differentiation of adult neural stem/progenitor cells (aNSPCs) and postnatal brain development. Fut8 depletion reduces the proliferation of aNSPCs and inhibits neuronal differentiation of aNSPCs in vitro and in vivo, respectively. Additionally, Fut8 deficiency impairs learning and memory in mice. Mechanistically, Fut8 directly interacts with integrin α6 (Itga6), an upstream regulator of the PI3k-Akt signaling pathway, and catalyzes core fucosylation of Itga6. Deletion of Fut8 enhances the ubiquitination of Itga6 by promoting the binding of ubiquitin ligase Trim21 to Itga6. Low levels of Itga6 inhibit the activity of the PI3K/Akt signaling pathway. Moreover, the Akt agonist SC79 can rescue neurogenic and behavioral deficits caused by Fut8 deficiency. In summary, our study uncovers an essential function of Fut8 and core fucosylation in regulating adult neurogenesis and sheds light on the underlying mechanisms.

7.
Heliyon ; 10(3): e25068, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38317927

RESUMEN

Utilizing a quantile frequency connectedness approach, we explore the connectedness between energy tokens, crypto market, and renewable energy stock markets. The empirical results show that the connectedness measures of the series are characterized by asymmetry and heterogeneity across quantiles and different investment horizons. Specifically, the characteristic of clustering has been observed that energy tokens and crypto market are more interconnected, while the renewable energy stock markets are more interconnected with each other at median quantile. The linkages between energy tokens and renewable energy stock markets are quite weak under normal market conditions, suggesting the diversification opportunities in investing these financial assets. However, these series are more interconnected under extreme market conditions, with the renewable energy stock markets are on the dominating end of the propagation mechanism while the energy tokens and crypto market are net receivers of shocks. Further frequency decomposition shows that this strategy can hold in the short term, while in the long term investors could benefit from the diversification opportunities by investing both kinds of financial assets. Additionally, the dynamic analysis affirms that the connectedness measures are varied and event-dependent over time. Our results may help investors and policymakers have a better assessment and portfolio management.

8.
ACS Appl Bio Mater ; 7(3): 1547-1557, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38346262

RESUMEN

African swine fever is an acute and highly contagious infectious disease with a mortality rate of up to 100%. The lack of commercial vaccines and drugs is a serious economic threat to the global pig industry. Cell-mediated immunity plays an essential role in protection against viral infection. We previously reported the rational design of a T-cell-activating thermostable scaffold (RPT) for antigen delivery and improved cellular immunity. We conjugated antigens P30, P54, P72, CD2 V, and CP312R to RPT, using a SpyCatcher/SpyTag covalent attachment strategy to construct nanovaccines (multiantigens-RPT). Multiantigens-RPT exhibited significantly higher thermal, storage, and freeze-thaw stability. The specific antibodies IgG and IgG2a of the multiantigen-RPT-immunized were higher than the antigens cocktail-immunized by approximately 10-100 times. ELISpot demonstrated that more IFN-γ-secreting cells were produced by the multiantigen-RPT-immunized than by the antigens cocktail-immunized. Delivery of the multiantigen nanovaccine by a T-cell-activating scaffold induced strong humoral and cellular immune responses in mice and pigs and is a potentially useful candidate vaccine for the African swine fever virus.


Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Porcinos , Animales , Ratones , Fiebre Porcina Africana/prevención & control , Linfocitos T , Nanovacunas , Adyuvantes Inmunológicos
9.
Urolithiasis ; 52(1): 15, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38117370

RESUMEN

The aim of the study was to analyze the factors influencing the efficacy of ultrasound-guided extracorporeal shockwave lithotripsy (ESWL) in the treatment of ureteral stones. The clinical data of 8102 patients (6083 men and 2019 women) who presented with ureteral stones were retrospectively analyzed. All the patients were treated with ultrasound-guided ESWL. The stone-free rate (SFR) was calculated to evaluate the effect of ESWL. The characteristics of the patients and their stones, and the ESWL parameters applied were compared to identify the factors affecting the treatment outcomes. The SFR and that following one ESWL session were 94.6% (7663/8102) and 75.4% (6107/8102), respectively. Multivariate analysis showed that stone location (OR 0.656, p < 0.001), stone size (OR 1.103, p < 0.001), and degree of hydronephrosis (OR 1.952, p < 0.001) independently affected SFR; and age (OR 1.005, p = 0.022), stone location (OR 0.729, p < 0.001), stone size (OR 1.103, p < 0.001), degree of hydronephrosis (OR 1.387, p = 0.001), maximum energy level(OR 0.691, p < 0.001) independently affected SFR following one session. Ultrasound-guided ESWL is effective in all levels of ureteral stones. Large stone size and moderate hydronephrosis are correlated with treatment failure. Ultrasound-guided ESWL may be the first choice for distal ureteral stones.


Asunto(s)
Hidronefrosis , Litotricia , Cálculos Ureterales , Masculino , Humanos , Femenino , Estudios Retrospectivos , Litotricia/efectos adversos , Cálculos Ureterales/diagnóstico por imagen , Cálculos Ureterales/terapia , Ultrasonografía Intervencional
10.
Theranostics ; 13(15): 5546-5560, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37908720

RESUMEN

Background and rationale: Attenuated Salmonella typhimurium VNP20009 has been used to treat tumor-bearing mice and entered phase I clinical trials. However, its mild anticancer effect in clinical trials may be related to insufficient bacterial colonization and notable adverse effects with increasing dosages. Guanosine 5'-diphosphate-3'-diphosphate (ppGpp) synthesis-deficient Salmonella is an attenuated strain with good biosafety and anticancer efficacy that has been widely investigated in various solid cancers in preclinical studies. Integration of the advantages of these two strains may provide a new solution for oncolytic bacterial therapy. Methods: We incorporated the features of ΔppGpp into VNP20009 and obtained the HCS1 strain by deleting relA and spoT, and then assessed its cytotoxicity in vitro and antitumor activities in vivo. Results: In vitro experiments revealed that the invasiveness and cytotoxicity of HCS1 to cancer cells were significantly lower than those of the VNP20009. Additionally, tumor-bearing mice showed robust cancer suppression when treated with different doses of HCS1 intravenously, and the survival time and cured mice were dramatically increased. Furthermore, HCS1 can increase the levels of pro-inflammatory cytokines in tumor tissues and relieve the immunosuppression in the tumor microenvironments. It can also recruit abundant immune cells into tumor tissues, thereby increasing immune activation responses. Conclusion: The newly engineered Salmonella HCS1 strain manifests high prospects for cancer therapeutics and is a promising option for future clinical cancer immunotherapy.


Asunto(s)
Neoplasias , Animales , Ratones , Neoplasias/terapia , Salmonella typhimurium/genética , Inmunoterapia , Microambiente Tumoral
11.
iScience ; 26(10): 107752, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37954141

RESUMEN

Symbiotic nitrogen fixation is a complex process in which legumes interact with rhizobia under nitrogen starvation. In this study, we found that myotubularin phosphatase (MtMP) is mainly expressed in roots and nodules in Medicago truncatula. MtMP promotes autophagy by dephosphorylating PtdIns3P on autophagosomes. The mp mutants inoculated with rhizobia showed a significant reduction in nitrogenase activity and significantly higher number of mitochondria than those of wild-type plants under nitrogen starvation, indicating that MtMP is involved in mitophagy of the infection zone. Mitophagy may provide carbon skeletons and nitrogen for the development of bacteroids and the reprogramming of infected cells. In conclusion, we found, for the first time, that myotubularin phosphatase is involved in autophagy in plants. MtMP-involved autophagy plays an active role in symbiotic nitrogen fixation. These results deepen our understanding of symbiotic nitrogen fixation.

12.
BMC Genomics ; 23(Suppl 5): 863, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37936055

RESUMEN

BACKGROUND: Genomic variants of the disease are often discovered nowadays through population-based genome-wide association studies (GWAS). Identifying genomic variations potentially underlying a phenotype, such as hypertension, in an individual is important for designing personalized treatment; however, population-level models, such as GWAS, may not capture all the important, individualized factors well. In addition, GWAS typically requires a large sample size to detect the association of low-frequency genomic variants with sufficient power. Here, we report an individualized Bayesian inference (IBI) algorithm for estimating the genomic variants that influence complex traits, such as hypertension, at the level of an individual (e.g., a patient). By modeling at the level of the individual, IBI seeks to find genomic variants observed in the individual's genome that provide a strong explanation of the phenotype observed in this individual. RESULTS: We applied the IBI algorithm to the data from the Framingham Heart Study to explore the genomic influences of hypertension. Among the top-ranking variants identified by IBI and GWAS, there is a significant number of shared variants (intersection); the unique variants identified only by IBI tend to have relatively lower minor allele frequency than those identified by GWAS. In addition, IBI discovered more individualized and diverse variants that explain hypertension patients better than GWAS. Furthermore, IBI found several well-known low-frequency variants as well as genes related to blood pressure that GWAS missed in the same cohort. Finally, IBI identified top-ranked variants that predicted hypertension better than GWAS, according to the area under the ROC curve. CONCLUSIONS: The results support IBI as a promising approach for complementing GWAS, especially in detecting low-frequency genomic variants as well as learning personalized genomic variants of clinical traits and disease, such as the complex trait of hypertension, to help advance precision medicine.


Asunto(s)
Estudio de Asociación del Genoma Completo , Hipertensión , Humanos , Estudio de Asociación del Genoma Completo/métodos , Teorema de Bayes , Polimorfismo de Nucleótido Simple , Fenotipo , Hipertensión/genética , Genómica
13.
Front Genet ; 14: 1230579, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37842648

RESUMEN

Background: Despite the recent success of genome-wide association studies (GWAS) in identifying 90 independent risk loci for Parkinson's disease (PD), the genomic underpinning of PD is still largely unknown. At the same time, accurate and reliable predictive models utilizing genomic or demographic features are desired in the clinic for predicting the risk of Parkinson's disease. Methods: To identify influential demographic and genomic factors associated with PD and to further develop predictive models, we utilized demographic data, incorporating 200 variables across 33,473 participants, along with genomic data involving 447,089 SNPs across 8,840 samples, both derived from the Fox Insight online study. We first applied correlation and GWAS analyses to find the top demographic and genomic factors associated with PD, respectively. We further developed and compared a variety of machine learning (ML) models for predicting PD. From the developed ML models, we performed feature importance analysis to reveal the predictability of each demographic or the genomic input feature for PD. Finally, we performed gene set enrichment analysis on our GWAS results to identify PD-associated pathways. Results: In our study, we identified both novel and well-known demographic and genetic factors (along with the enriched pathways) related to PD. In addition, we developed predictive models that performed robustly, with AUC = 0.89 for demographic data and AUC = 0.74 for genomic data. Our GWAS analysis identified several novel and significant variants and gene loci, including three intron variants in LMNA (p-values smaller than 4.0e-21) and one missense variant in SEMA4A (p-value = 1.11e-26). Our feature importance analysis from the PD-predictive ML models highlighted some significant and novel variants from our GWAS analysis (e.g., the intron variant rs1749409 in the RIT1 gene) and helped identify potentially causative variants that were missed by GWAS, such as rs11264300, a missense variant in the gene DCST1, and rs11584630, an intron variant in the gene KCNN3. Conclusion: In summary, by combining a GWAS with advanced machine learning models, we identified both known and novel demographic and genomic factors as well as built well-performing ML models for predicting Parkinson's disease.

14.
ACS Infect Dis ; 9(11): 2358-2368, 2023 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-37861250

RESUMEN

African swine fever (ASF) is caused by the African swine fever virus (ASFV) and is a highly contagious, acute, febrile disease that has high morbidity and mortality rates in domestic and wild swine. However, a safe and effective vaccine against ASF remains unavailable as single antigens fail to provide sufficient protection. Therefore, a combination of multiple antigens with an efficient delivery system might be an alternative strategy. Herein, a de novo-designed antigen with multiple T-cell epitopes (TEPs) of ASFV was conjugated for surface display on self-assembled nanoparticles (NPs) of Aquifex aeolicus lumazine synthase (AaLS) and Quasibacillus thermotolerans encapsulin (QT) through the SpyCatcher/SpyTag system to construct nanovaccines (TEP-Spy-NPs). TEP-Spy-NPs exhibited significantly more thermal, storage, and freeze-thaw stability in comparison to TEP monomers. TEP-Spy-NPs were highly immunogenic and induced strong polyclonal antibody responses in mice and pigs. The specific antibody titers against the TEP of the TEP-Spy-AaLS and TEP-Spy-QT groups were significantly higher than those of the TEP monomer immune group after the second booster immunization. The antibody titer against TEP of the TEP-Spy-QT group was approximately twice that of the TEP-Spy-AaLS group in mice. ELISpot analysis demonstrated that more IFN-γ- and IL-2-secreting splenic lymphocytes were produced by TEP-Spy-AaLS- and TEP-Spy-QT-immunized mice than by TEP monomer-immunized mice. TEP-Spy-NPs elicited stronger cellular immunity and in vivo immunity in immunized pigs than did TEP monomers. Thus, the TEP nanovaccine successfully induced strong humoral and cellular immune responses in mice and pigs, and TEP-Spy-NPs have the potential as candidate vaccines for ASFV.


Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Virus de la Fiebre Porcina Clásica , Nanopartículas , Animales , Porcinos , Ratones , Fiebre Porcina Africana/prevención & control , Formación de Anticuerpos , Linfocitos T
15.
Molecules ; 28(17)2023 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-37687055

RESUMEN

The changes in the working environment have necessitated greater requirements in terms of the long-term anti-corrosion ability of metal anti-corrosion coatings, and the emergence of intelligent coatings has met this demand. A nanocontainer with a hydrophobic inner cavity and hydrophilic outer cavity called ß-cyclodextrin (ß-CD) was grafted onto the surface of hydroxyapatite (HAp) with a silane coupling agent, encapsulating benzotriazole (BTA) and embedded in epoxy resin to improve the coating anticorrosion performance. The excellent corrosion resistance of the coating in immersion and scratch experiments was derived from the inert protective layer formed by the reaction of the rapidly released corrosion inhibitor with the corrosion products on the metal surface. After 30 days of immersion experiment, the coating could still maintain the low-frequency impedance value of 6.28 × 107 Ω cm2. In this work, the enhancement of the physical barrier function of HAp nanoparticle and the pH-response function conferred by ß-cyclodextrin provided the coating with good passive and active acting abilities in corrosive environments, respectively.

16.
Microorganisms ; 11(9)2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37764165

RESUMEN

The Brucella type IV secretion system (T4SS) can promote the intracellular survival and reproduction of Brucella. T4SS secretes effector proteins to act on cellular signaling pathways to inhibit the host's innate immune response and cause a chronic, persistent Brucella infection. Brucella can survive in host cells for a long time by inhibiting macrophage apoptosis and avoiding immune recognition. The effector protein, BspF, secreted by T4SS, can regulate host secretory transport and accelerate the intracellular replication of Brucella. BspF has an acetyltransferase domain of the GNAT (GCN5-related N-acetyltransferases) family, and in our previous crotonylation proteomics data, we have found that BspF has crotonyl transferase activity and crotonylation regulation of host cell protein in the proteomics data. Here, we found that BspF attenuates the crotonylation modification of the interacting protein p53, which reduces the p53 expression through the GNAT domain. BspF can inhibit the transcription and protein expression of downstream apoptotic genes, thereby inhibiting host cell apoptosis. Additionally, the Brucella ΔbspF mutant stain promotes apoptosis and reduces the survival rate of Brucella in the cells. In conclusion, we identified that the T4SS effector protein BspF can regulate host cell apoptosis to assist Brucella in its long-term survival by attenuating crotonylation modification of p53 and decreasing p53 expression. Our findings reveal a unique mechanism of elucidating how Brucella regulates host cell apoptosis and promotes its proliferation through the secretion of effector proteins.

17.
World J Psychiatry ; 13(7): 453-460, 2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37547736

RESUMEN

BACKGROUND: Treatment-refractory schizophrenia (TRS), accounting for approximately 30% of all schizophrenia cases, has poor treatment response and prognosis despite treatment with antipsychotic drugs. AIM: To analyze the therapeutic effectiveness of repetitive transcranial magnetic stimulation (rTMS) combined with olanzapine (OLZ) and amisulpride (AMI) for TRS and its influence on the patient's cognitive function. METHODS: This study enrolled 114 TRS patients who received treatment at the First Affiliated Hospital of Zhengzhou University between July 2019 and July 2022. In addition to the basic OLZ + AMI therapy, 54 cases of the control group (Con group) received modified electroconvulsive therapy, while 60 cases of the research group (Res group) received rTMS. Data on therapeutic effectiveness, safety (incidence of drowsiness, headache, nausea, vomiting, or memory impairment), Positive and Negative Symptom Scale, Montreal Cognitive Assessment Scale, and Schizophrenia Quality of Life Scale were collected from both cohorts for comparative analyses. RESULTS: The Res group elicited a higher overall response rate and better safety profile when compared with the Con group. Additionally, a significant reduction was observed in the post-treatment Positive and Negative Symptom Scale and Schizophrenia Quality of Life Scale scores of the Res group, presenting lower scores than those of the Con group. Furthermore, a significant increase in the Montreal Cognitive Assessment Scale score was reported in the Res group, with higher scores than those of the Con group. CONCLUSION: The treatment of TRS with rTMS and OLZ + AMI is effective and safe. Moreover, it can alleviate the patients' mental symptoms, improve their cognitive function and quality of life, and has a high clinical application value.

19.
Environ Pollut ; 334: 122172, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37437760

RESUMEN

Rice paddies are unique artificial wetlands generating methylmercury (MeHg), a highly potent neurotoxin. However, the impact of diverse mercury (Hg) pools on the Hg-methylating communities during rice growth is unclear. This study investigates soil treated with five mercury forms (HgCl2, α-HgS, ß-HgS, nano-HgS, and Hg-DOM) at two levels (5 mg/kg and 50 mg/kg). The results showed a varying abundance of sulphate-reducing bacteria, Geobacteraceae, methanogens, and hgcA microbes in the soils across rice grown under different mercury treatments and concentrations. Soils treated with HgCl2, nano-HgS and ß-HgS had higher than average levels of hgcA-methanogen abundance, and the abundance significantly and positively correlated with MeHg concentration in all samples (p < 0.05). The shifting trends in Hg-methylating microbial structure following treatment with α-HgS, ß-HgS, nano-HgS and Hg-DOM at both 5 and 50 mg/kg Hg levels were diverse compared with the control group. HgCl2 treatment showed contrasting trends in community distribution of Hg methylators at 5 and 50 mg/kg Hg levels during rice growth. Dissolved organic carbon, redox potential and sulphate levels significantly correlated with variation in the Hg-methylating microbial community structure and MeHg production in soils.


Asunto(s)
Mercurio , Compuestos de Metilmercurio , Oryza , Contaminantes del Suelo , Mercurio/análisis , Compuestos de Metilmercurio/química , Suelo/química , Contaminantes del Suelo/análisis , Oryza/química , Sulfatos
20.
Viruses ; 15(7)2023 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-37515122

RESUMEN

As one of the most important avian immunosuppressive and neoplastic diseases, Marek's disease (MD), caused by oncogenic Marek's disease virus (MDV), has caused huge economic losses worldwide over the past five decades. In recent years, MD outbreaks have occurred frequently in MD-vaccinated chicken flocks, but the key pathogenic determinants and influencing factors remain unclear. Herein, we analyzed the pathogenicity of seven newly isolated MDV strains from tumor-bearing chickens in China and found that all of them were pathogenic to chicken hosts, among which four MDV isolates, SDCW01, HNXZ05, HNSQ05 and HNSQ01, were considered to be hypervirulent MDV (HV-MDV) strains. At 73 days of the virus infection experiment, the cumulative incidences of MD were 100%, 93.3%, 90% and 100%, with mortalities of 83.3%, 73.3%, 60% and 86.7%, respectively, for the four viruses. The gross occurrences of tumors were 50%, 33.3%, 30% and 63.3%, respectively, accompanied by significant hepatosplenomegaly and serious atrophy of the immune organs. Furthermore, the immune protection effects of four commercial MD vaccines against SDCW01, CVI988, HVT, CVI988+HVT, and 814 were explored. Unexpectedly, during the 67 days of post-virus challenge, the protection indices (PIs) of these four MD vaccines were only 46.2%, 38.5%, 50%, and 28%, respectively, and the birds that received the monovalent CVI988 or HVT still developed tumors with cumulative incidences of 7.7% and 11.5%, respectively. To our knowledge, this is the first demonstration of the simultaneous comparison of the immune protection efficacy of multiple commercial MD vaccines with different vaccine strains. Our study revealed that the HV-MDV variants circulating in China could significantly break through the immune protection of the classical MD vaccines currently widely used. For future work, there is an urgent need to develop novel, more effective MD vaccines for tackling the new challenge of emerging HV-MDV strains or variants for the sustainable control of MD.


Asunto(s)
Herpesvirus Gallináceo 2 , Vacunas contra la Enfermedad de Marek , Enfermedad de Marek , Neoplasias , Animales , Pollos , Herpesvirus Gallináceo 2/genética , Vacunas contra la Enfermedad de Marek/genética
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