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1.
New Phytol ; 241(4): 1794-1812, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38135652

RESUMO

The SWI/SNF complex is guided to the promoters of designated genes by its co-operator to activate transcription in a timely and appropriate manner to govern development, pathogenesis, and stress responses in fungi. Nevertheless, knowledge of the complexes and their co-operator in phytopathogenic fungi is still fragmented. We demonstrate that the heat shock transcription factor SsHsf1 guides the SWI/SNF complex to promoters of heat shock protein (hsp) genes and antioxidant enzyme genes using biochemistry and pharmacology. This is accomplished through direct interaction with the complex subunit SsSnf5 under heat shock and oxidative stress. This results in the activation of their transcription and mediates histone displacement to maintain reactive oxygen species (ROS) homeostasis. Genetic results demonstrate that the transcription module formed by SsSnf5 and SsHsf1 is responsible for regulating morphogenesis, stress tolerance, and pathogenicity in Sclerotinia sclerotiorum, especially by directly activating the transcription of hsp genes and antioxidant enzyme genes counteracting plant-derived ROS. Furthermore, we show that stress-induced phosphorylation of SsSnf5 is necessary for the formation of the transcription module. This study establishes that the SWI/SNF complex and its co-operator cooperatively regulate the transcription of hsp genes and antioxidant enzyme genes to respond to host and environmental stress in the devastating phytopathogenic fungi.


Assuntos
Ascomicetos , Proteínas de Ligação a DNA , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/metabolismo , Espécies Reativas de Oxigênio , Antioxidantes , Virulência , Proteínas de Choque Térmico/metabolismo , Homeostase
2.
Langmuir ; 40(20): 10518-10525, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38719232

RESUMO

The practical utilization of the hydrogen evolution reaction (HER) necessitates the creation of electrocatalysts that are both efficient and abundant in earth elements, capable of operating effectively within a wide pH range. However, this objective continues to present itself as an arduous obstacle. In this research, we propose the incorporation of sulfur vacancies in a novel heterojunction formed by MoS2@CoS2, designed to exhibit remarkable catalytic performances. This efficacy is attributed to the advantageous combination of the low work function and space charge zone at the interface between MoS2 and CoS2 in the heterojunction. The MoS2@CoS2 heterojunction manifests outstanding hydrogen evolution activity over an extensive pH range. Remarkably, achieving a current density of 10 mA cm-2 in aqueous solutions 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline (PBS), respectively, requires only an overpotential of 48, 62, and 164 mV. The Tafel slopes for each case are 43, 32, and 62 mV dec-1, respectively. In this study, the synergistic effect of MoS2 and CoS2 is conducive to electron transfer, making the MoS2@CoS2 heterojunction show excellent electrocatalytic performance. The synergistic effects arising from the heterojunction and sulfur vacancy not only contribute to the observed catalytic prowess but also provide a valuable model and reference for the exploration of other efficient electrocatalysts. This research marks a significant stride toward overcoming the challenges associated with developing electrocatalysts for practical hydrogen evolution applications.

3.
BMC Med Res Methodol ; 24(1): 41, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365610

RESUMO

BACKGROUND: Missing data is frequently an inevitable issue in cohort studies and it can adversely affect the study's findings. We assess the effectiveness of eight frequently utilized statistical and machine learning (ML) imputation methods for dealing with missing data in predictive modelling of cohort study datasets. This evaluation is based on real data and predictive models for cardiovascular disease (CVD) risk. METHODS: The data is from a real-world cohort study in Xinjiang, China. It includes personal information, physical examination data, questionnaires, and laboratory biochemical results from 10,164 subjects with a total of 37 variables. Simple imputation (Simple), regression imputation (Regression), expectation-maximization(EM), multiple imputation (MICE) , K nearest neighbor classification (KNN), clustering imputation (Cluster), random forest (RF), and decision tree (Cart) were the chosen imputation methods. Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) are utilised to assess the performance of different methods for missing data imputation at a missing rate of 20%. The datasets processed with different missing data imputation methods were employed to construct a CVD risk prediction model utilizing the support vector machine (SVM). The predictive performance was then compared using the area under the curve (AUC). RESULTS: The most effective imputation results were attained by KNN (MAE: 0.2032, RMSE: 0.7438, AUC: 0.730, CI: 0.719-0.741) and RF (MAE: 0.3944, RMSE: 1.4866, AUC: 0.777, CI: 0.769-0.785). The subsequent best performances were achieved by EM, Cart, and MICE, while Simple, Regression, and Cluster attained the worst performances. The CVD risk prediction model was constructed using the complete data (AUC:0.804, CI:0.796-0.812) in comparison with all other models with p<0.05. CONCLUSION: KNN and RF exhibit superior performance and are more adept at imputing missing data in predictive modelling of cohort study datasets.


Assuntos
Algoritmos , Doenças Cardiovasculares , Humanos , Estudos de Coortes , Aprendizado de Máquina , Máquina de Vetores de Suporte , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia
4.
Inorg Chem ; 63(15): 6776-6786, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38572830

RESUMO

The heme-containing chlorite dismutases catalyze the rapid and efficient decomposition of chlorite (ClO2-) to yield Cl- and O2, and the catalytic efficiency of chlorite dismutase from Dechloromonas aromatica (DaCld) in catalyzing the decomposition of bromite (BrO2-) was dependent on pH, which was supposed to be caused by the conversion of active Cpd I to the inactive Cpd II by proton-coupled electron transfer (PCET) from the pocket Tyr118 to the propionate side chain of heme at high pH. However, the direct evidence of PCET and how the pH affects the efficiency of DaCld, as well as whether Cpd II is really inactive, are still poorly understood. Here, on the basis of the high-resolution crystal structures, the computational models in both acidic (pH 5.0) and alkaline (pH 9.0) environments were constructed, and a series of quantum mechanical/molecular mechanical calculations were performed. On the basis of our calculation results, the O-Br bond cleavage of BrO2- always follows the homolytic mode to generate Cpd II rather than Cpd I. It is different from the O-O cleavage of O2/H2O2 or peracetic acid catalyzed by the other heme-containing enzymes. Thus, in the subsequent O-O rebound reaction, it is the Fe(IV)═O in Cpd II that combines with the O-Br radical. Because the porphyrin ring in Cpd II does not bear an unpaired electron, the previously suggested PCET from Tyr118 to the propionate side chain of heme was not theoretically recognized in an alkaline environment. In addition, the O-O rebound step in an alkaline solution corresponds to an energy barrier that is larger than that in an acidic environment, which can well explain the pH dependence of the activity of DaCld. In addition, the protonation state of the propionic acid side chains of heme and the surrounding hydrogen bond networks were calculated to have a significant impact on the barriers of the O-O rebound step, which is mainly achieved by affecting the reactivity of the Fe(IV)═O group in Cpd II. In an acidic environment, the relatively weaker coordination of the O2 atom to Fe leads to its higher reactivity toward the O-O rebound reaction. These observations may provide useful information for understanding the catalysis of chlorite dismutases.


Assuntos
Betaproteobacteria , Cloretos , Peróxido de Hidrogênio , Oxirredutases , Propionatos , Peróxido de Hidrogênio/química , Catálise , Prótons , Concentração de Íons de Hidrogênio , Heme/química
5.
Fish Shellfish Immunol ; 146: 109428, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325594

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease in the world. Immunity is the major contributing factor in NAFLD; however, the interaction of immune cells and hepatocytes in disease progression has not been fully elucidated. As a popular species for studying NAFLD, zebrafish, whose liver is a complex immune system mediated by immune cells and non-immune cells in maintaining immune tolerance and homeostasis. Understanding the cellular composition and immune environment of zebrafish liver is of great significance for its application in NAFLD. Here, we established a liver atlas that consists of 10 cell types using single-cell RNA sequencing (scRNA-seq). By examining the heterogeneity of hepatocytes and analyzing the expression of NAFLD-associated genes in the specific cluster, we provide a potential target cell model to study NAFLD. Additionally, our analysis identified two subtypes of distinct resident macrophages with inflammatory and non-inflammatory functions and characterized the successive stepwise development of T cell subclusters in the liver. Importantly, we uncovered the possible regulation of macrophages and T cells on target cells of fatty liver by analyzing the cellular interaction between hepatocytes and immune cells. Our data provide valuable information for an in-depth study of immune cells targeting hepatocytes to regulate the immune balance in NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Peixe-Zebra/genética , Transcriptoma , Fígado/metabolismo , Hepatócitos/metabolismo , Comunicação Celular
6.
BMC Pregnancy Childbirth ; 24(1): 9, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166803

RESUMO

BACKGROUND: Intractable postpartum hemorrhage (PPH) during cesarean section has been a significant concern for obstetricians. We aimed to explore the effectiveness and safety of a new type of uterine compression suture, the step-wise surgical technique of knapsack-like sutures for treating intractable PPH caused by uterine atony and placenta factors in cesarean section. METHODS: The step-wise surgical technique of knapsack-like sutures was established on the basis of the artful combination of vertical strap-like sutures and an annular suture-ligation technique. This novel surgical technique was applied to 34 patients diagnosed with PPH during cesarean section due to severe uterine atony and placental factors in our department. The hemostatic effects, clinical outcomes and follow-up visit results were all reviewed and analyzed. RESULTS: This new uterine compression suture successfully stopped bleeding in 33 patients, and the effective rate was 97.06%. Only 1 patient failed and was changed to use bilateral uterine arterial embolization and internal iliac artery embolization. The follow-up visits indicated that 33 patients restored menstruation except for 1 who was diagnosed with amenorrhea. The gynecological ultrasound tests of all the patients suggested good uterine involutions, and they had no obvious complaints such as hypogastralgia. CONCLUSIONS: This step-wise surgical technique of knapsack-like uterine compression sutures can compress the uterus completely. It is a technique that can conserve the uterus and fertility function without special equipment in caesarean section for PPH, with the characteristics of being safe, simple and stable (3 S) with rapid surgery, reliable hemostasis and resident doctor to operation (3R).


Assuntos
Hemorragia Pós-Parto , Inércia Uterina , Feminino , Humanos , Gravidez , Hemorragia Pós-Parto/cirurgia , Hemorragia Pós-Parto/etiologia , Cesárea/efeitos adversos , Inércia Uterina/cirurgia , Hemostasia Cirúrgica/métodos , Placenta/cirurgia , Útero/cirurgia , Útero/irrigação sanguínea , Suturas/efeitos adversos , Técnicas de Sutura/efeitos adversos
7.
J Exp Child Psychol ; 243: 105917, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38579588

RESUMO

The difference between the audiovisual incongruent condition and the audiovisual congruent condition is known as cross-modal conflict, which is an important behavioral index to measure the conflict control function. Previous studies have found conflict control deficits in children with attention-deficit/hyperactivity disorder (ADHD), but it is not clear whether and how cross-modal conflict occurs in children with ADHD at different processing levels. The current study adopted the cross-modal matching paradigm to recruit 25 children with ADHD (19 boys and 6 girls) and 24 TD children (17 boys and 7 girls), aiming to investigate the cross-modal conflict effect at the perception and response levels of children with ADHD. The results showed that both groups of children showed significant cross-modal conflict, and there was no significant difference between the ADHD and TD groups in the number of error trials and mean response time. However, the cross-modal conflict effect caused by auditory distractors was different between the ADHD and TD groups; the TD group had stronger auditory conflict at the response level, whereas the ADHD group had weaker auditory conflict. This indicates that the ADHD group had a deficit of auditory conflict at the response level.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Percepção Auditiva , Conflito Psicológico , Humanos , Masculino , Feminino , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Tempo de Reação , Percepção Visual/fisiologia , Atenção , Estimulação Luminosa
8.
J Exp Child Psychol ; 238: 105798, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37844345

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that leads to visually relevant compensatory activities and cognitive strategies in children. Previous studies have identified difficulties with audiovisual integration in children with ADHD, but the characteristics of the visual dominance effect when processing multisensory stimuli are not clear in children with ADHD. The current study used the Colavita paradigm to explore the visual dominance effect in school-aged children with ADHD. The results found that, compared with typically developing children, children with ADHD had a higher proportion of "visual-auditory" trials and a lower proportion of "simultaneous" trials. The study also found that the proportion of visual-auditory trials in children with ADHD decreased as their Swanson, Nolan, and Pelham-IV rating scale (SNAP-IV) inattention scores increased. The results showed that school-aged children with ADHD had a larger Colavita effect, which decreased with the severity of inattentive symptoms. This may be due to an overreliance on visual information and an abnormal integration time window. The connection between multisensory cognitive processing performance and clinical symptoms found in the current study provides empirical and theoretical support for the knowledge base of multisensory and cognitive abilities in disorders.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Criança , Cognição
9.
Inorg Chem ; 62(33): 13230-13240, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37561650

RESUMO

The H2O2-dependent degradation of haloindole catalyzed by the dehaloperoxidase (DHP) from Amphitrite ornate has been reported to employ the peroxygenase mechanism, and the two oxidized products 5-halo-2-oxindole and 5-halo-3-oxindole have a similar amount. According to a previous experimental study, compound I (Cpd I) was suggested to be responsible for triggering the reaction, and the reaction may undergo three possible intermediates; however, the reaction details are still unclear. To clarify the reaction mechanism of DHP, the computational model was constructed on the basis of the high-resolution crystal structure, and a series of the quantum mechanical/molecular mechanical calculations were performed. Based on our calculation results, it is confirmed that the reaction starts from the direct electrophilic attack of Cpd I on the indole ring of the substrate, and the resulted intermediate contains both a carbocation and an oxygen anion, whereas the common hydrogen abstraction by Cpd I was calculated to correspond to a relatively higher barrier. In addition, a net electron transfer from the substrate to the iron center is observed during the attack of Cpd I on the indole ring; therefore, the carbocation/oxygen anion intermediate can easily undergo an intramolecular hydride transfer to form the product 5-halo-2-oxindole or isomerize to the epoxide intermediate which finally generates another product 5-halo-3-oxindole. It is the zwitterionic characteristic of the intermediate that makes the intermolecular hydride transfer quite easy, and it is the high electron affinity of the iron center that promotes the single-electron oxidation of the reaction intermediate. Our calculations well explain the formation of two oxidized products 5-halo-2-oxindole and 5-halo-3-oxindole.


Assuntos
Peróxido de Hidrogênio , Peroxidases , Peroxidases/química , Oxindóis , Peróxido de Hidrogênio/metabolismo , Hemoglobinas/química , Hemoglobinas/metabolismo , Elétrons , Oxigênio/química , Ferro
10.
J Chem Inf Model ; 63(9): 2759-2768, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37100030

RESUMO

The AAD-1 enzyme belongs to the Fe(II) and α-ketoglutarate (Fe/αKG)-dependent nonheme aryloxyalkanoate dioxygenase family (AADs), which catalyzes the breakdown of 2,4-dichlorophenoxyacetic acid (2,4-D, an active ingredient of thousands of commercial herbicides) by using the highly active Fe(IV)═O complex. Multiple species of bacteria degrade 2,4-D via a pathway initiated by AADs; however, the detail of how they promote the cleavage of the ether C-O bond to generate 2,4-dichlorophenol (2,4-DCP) and glyoxylate is still unclear, which is the prerequisite for the further degradation of these halogenated aromatics. In this work, based on the crystal structure of AAD-1, the computational models were constructed, and a series of QM/MM and QM-only calculations were performed to explore the cleavage of the ether bond in 2,4-D with the catalysis of AAD-1. Our calculations reveal that AAD-1 may be only responsible for the hydroxylation of the substrate to generate the intermediate hemiacetal, which corresponds to an overall energy barrier of 14.2 kcal/mol on the quintet state surface, and the decomposition of the hemiacetal in the active site center of AAD-1 was calculated to be rather slow, corresponding to an energy barrier of 24.5 kcal/mol. In contrast, the decomposition of the free hemiacetal molecule in a solvent was calculated to be quite easy. Whether the decomposition of the hemiacetal occurs inside or outside the activation site is still worthy of experimental verification.


Assuntos
Dioxigenases , Herbicidas , Herbicidas/metabolismo , Ácidos Cetoglutáricos/metabolismo , Dioxigenases/química , Dioxigenases/metabolismo , Fenoxiacetatos , Ácido 2,4-Diclorofenoxiacético/metabolismo , Compostos Ferrosos/química
11.
Clin Invest Med ; 46(3): E13-18, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37769274

RESUMO

BACKGROUND: H19 is the first long noncoding RNA (lncRNA) found to be associated with gene imprinting. It is highly expressed in the embryonic stage and may have important regulatory effects on human embryonic development. We investigated the differences between the levels of H19 promoter DNA methylation in the chorionic villi of patients who experienced spontaneous abortion (SA) following in vitro fertilization embryo transfer (IVF-ET) and those of patients with a normal early pregnancy (NEP). We also analyzed the associated DNA methyltransferase (DNMT) activity. METHODS: Chorionic villus tissue from patients with SA and NEP were collected. The DNA methylation levels of two CpG islands in the promoter region of the H19 gene in the two groups were detected by bisulfite sequencing, and the mRNA expression of DNMTs was analyzed by real-time polymerase chain reaction. RESULTS: The sample size of each group was 32, and there were no significant differences in baseline data, including age, parity, and body mass index, between the two groups. Among the 7 CpG islands measured, the methylation rates of 3 CpG islands (CpG 1, 6, and 7) were significantly lower in the SA group than in the NEP group (P < 0.01). The methylation levels of the other 4 CpG islands were not significantly different between the two groups. There were no differences in the expression of DNMT1 between the two groups (P > 0.05), but DNMT3a and DNMT3b RNA levels were significantly lower in SA group than in the NEP group (P < 0.01). CONCLUSIONS: The lower H19 promoter DNA methylation levels found in the chorionic villi of patients with SA patients following IVF-ET may be explained by decreased expression of DNMT3a and DNMT3b.


Assuntos
Metilação de DNA , Fertilização in vitro , Impressão Genômica , Feminino , Humanos , Gravidez , Transferência Embrionária , Regiões Promotoras Genéticas , Aborto Espontâneo
12.
BMC Public Health ; 23(1): 242, 2023 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-36737734

RESUMO

BACKGROUND: Gallbladder disease (GBD) can increase the risk of cardiovascular disease (CVD). However, GBD has rarely been reported in the less developed, rural areas of Xinjiang. This study aimed to determine the prevalence of GBD and incidence of CVD in a prospective cohort study in rural Xinjiang. Moreover, the study aimed to explore the association between GBD and CVD within this cohort. METHODS: The study cohort included 11,444 Uyghur adults in Xinjiang, 3rd division, from the 51st Mission. Study groups were classified according to whether GBD was present or absent at baseline. The occurrence of CVD was the end event. Demographic, anthropometric, and biochemical data were recorded, and the incidence of CVD in the GBD and non-GBD groups analysed. Cox proportional hazards regression models were used to assess the association between GBD and CVD and factors associated with their incidence. Several subgroup analyses were performed to assess CVD incidence in different subgroups. The interaction between GBD and cardiometabolic risk factors, and subsequent risk of developing CVD, was evaluated. RESULTS: Prevalence of GBD in the study cohort was 10.29%. After a median follow-up of 4.92 years, the cumulative incidence of CVD in the study cohort was 10.49%, 8.43% in males and 12.65% in females. CVD incidence was higher in the GBD group (34.04% vs. 7.78%, HR = 4.96, 95% CI: 4.40-5.59). After multivariate adjustment, the risk of CVD remained higher in the GBD group (HR = 2.89, 95% CI: 2.54-3.29). Subgroup analyses showed male sex, smoking, alcohol consumption, lack of exercise, and abnormal renal function were all associated with increased risk of CVD. Moreover, the risk of CVD was markedly higher in GBD combined with cardiometabolic risk factors (hypertension, T2DM, dyslipidaemia, overweight, and abdominal obesity), than in cardiometabolic risk factors alone and this was higher in the GBD group than in the non-GBD group regardless of whether cardiometabolic risk factors were combined. CONCLUSION: GBD is an important independent risk factor for CVD development. Awareness of these associations will raise concerns among clinicians about the risk of cardiovascular disease in patients with GBD.


Assuntos
Doenças Cardiovasculares , Doenças da Vesícula Biliar , Hipertensão , Adulto , Feminino , Humanos , Masculino , Doenças Cardiovasculares/etiologia , Estudos Prospectivos , Hipertensão/epidemiologia , Fatores de Risco , Incidência , Doenças da Vesícula Biliar/epidemiologia , Doenças da Vesícula Biliar/complicações
13.
BMC Public Health ; 23(1): 1041, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37264356

RESUMO

PURPOSE: With the increase in aging and cardiovascular risk factors, the morbidity and mortality of atherosclerotic cardiovascular disease (ASCVD), represented by ischemic heart disease and stroke, continue to rise in China. For better prevention and intervention, relevant guidelines recommend using predictive models for early detection of ASCVD high-risk groups. Therefore, this study aims to establish a population ASCVD prediction model in rural areas of Xinjiang using survival analysis. METHODS: Baseline cohort data were collected from September to December 2016 and followed up till June 2022. A total of 7975 residents (4054 males and 3920 females) aged 30-74 years were included in the analysis. The data set was divided according to different genders, and the training and test sets ratio was 7:3 for different genders. A Cox regression, Lasso-Cox regression, and random survival forest (RSF) model were established in the training set. The model parameters were determined by cross-validation and parameter tuning and then verified in the training set. Traditional ASCVD prediction models (Framingham and China-PAR models) were constructed in the test set. Different models' discrimination and calibration degrees were compared to find the optimal prediction model for this population according to different genders and further analyze the risk factors of ASCVD. RESULTS: After 5.79 years of follow-up, 873 ASCVD events with a cumulative incidence of 10.19% were found (7.57% in men and 14.44% in women). By comparing the discrimination and calibration degrees of each model, the RSF showed the best prediction performance in males and females (male: Area Under Curve (AUC) 0.791 (95%CI 0.767,0.813), C statistic 0.780 (95%CI 0.730,0.829), Brier Score (BS):0.060, female: AUC 0.759 (95%CI 0.734,0.783) C statistic was 0.737 (95%CI 0.702,0.771), BS:0.110). Age, systolic blood pressure (SBP), apolipoprotein B (APOB), Visceral Adiposity Index (VAI), hip circumference (HC), and plasma arteriosclerosis index (AIP) are important predictors of ASCVD in the rural population of Xinjiang. CONCLUSION: The performance of the ASCVD prediction model based on the RSF algorithm is better than that based on Cox regression, Lasso-Cox, and the traditional ASCVD prediction model in the rural population of Xinjiang.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Humanos , Masculino , Feminino , Doenças Cardiovasculares/epidemiologia , Medição de Risco , População Rural , Aterosclerose/epidemiologia , Fatores de Risco , Análise de Sobrevida
14.
Proc Natl Acad Sci U S A ; 117(39): 24243-24250, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32929037

RESUMO

The necrotrophic fungal pathogen Cochliobolus victoriae produces victorin, a host-selective toxin (HST) essential for pathogenicity to certain oat cultivars with resistance against crown rust. Victorin is a mixture of highly modified heterodetic cyclic hexapeptides, previously assumed to be synthesized by a nonribosomal peptide synthetase. Herein, we demonstrate that victorin is a member of the ribosomally synthesized and posttranslationally modified peptide (RiPP) family of natural products. Analysis of a newly generated long-read assembly of the C. victoriae genome revealed three copies of precursor peptide genes (vicA1-3) with variable numbers of "GLKLAF" core peptide repeats corresponding to the victorin peptide backbone. vicA1-3 are located in repeat-rich gene-sparse regions of the genome and are loosely clustered with putative victorin biosynthetic genes, which are supported by the discovery of compact gene clusters harboring corresponding homologs in two distantly related plant-associated Sordariomycete fungi. Deletion of at least one copy of vicA resulted in strongly diminished victorin production. Deletion of a gene encoding a DUF3328 protein (VicYb) abolished the production altogether, supporting its predicted role in oxidative cyclization of the core peptide. In addition, we uncovered a copper amine oxidase (CAO) encoded by vicK, in which its deletion led to the accumulation of new glycine-containing victorin derivatives. The role of VicK in oxidative deamination of the N-terminal glycyl moiety of the hexapeptides to the active glyoxylate forms was confirmed in vitro. This study finally unraveled the genetic and molecular bases for biosynthesis of one of the first discovered HSTs and expanded our understanding of underexplored fungal RiPPs.


Assuntos
Ascomicetos/metabolismo , Proteínas Fúngicas/metabolismo , Micotoxinas/metabolismo , Ascomicetos/genética , Desaminação , Proteínas Fúngicas/genética , Proteínas Fúngicas/toxicidade , Deleção de Genes , Família Multigênica , Micotoxinas/genética , Micotoxinas/toxicidade , Biossíntese de Proteínas , Processamento de Proteína Pós-Traducional
15.
Angew Chem Int Ed Engl ; 62(4): e202212942, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36413636

RESUMO

The LiOH-based cathode chemistry has demonstrated potential for high-energy Li-O2 batteries. However, the understanding of such complex chemistry remains incomplete. Herein, we use the combined experimental methods with ab initio calculations to study LiOH chemistry. We provide a unified reaction mechanism for LiOH formation during discharge via net 4 e- oxygen reduction, in which Li2 O2 acts as intermediate in low water-content electrolyte but LiHO2 as intermediate in high water-content electrolyte. Besides, LiOH decomposes via 1 e- oxidation during charge, generating surface-reactive hydroxyl species that degrade organic electrolytes and generate protons. These protons lead to early removal of LiOH, followed by a new high-potential charge plateau (1 e- water oxidation). At following cycles, these accumulated protons lead to a new high-potential discharge plateau, corresponding to water formation. Our findings shed light on understanding of 4 e- cathode chemistries in metal-air batteries.

16.
Ann Hum Genet ; 86(5): 278-289, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35394066

RESUMO

PURPOSE: The polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene C677T has been linked to H-type hypertension. But the conclusion remained controversial. To elucidate this issue, we performed a comprehensive meta-analysis to analyze the MTHFR C677T polymorphism and H-type hypertension. MATERIALS AND METHODS: The English and Chinese databases were systematically searched to identify relevant studies until November 2020. RevMan 5.3 and Stata 12.0 software were used for meta-analysis. The odds ratio (ORs) and 95% confidence intervals (95% CIs) were used to assess the relationship between the MTHFR C677T polymorphism and H-type hypertension. RESULTS: A total of 14 studies involving 1769 cases and 1443 controls were included. The meta-analysis results showed the association between MTHFR C677T polymorphism and H-type hypertension with the homozygous codominant model (OR = 3.30, 95% CI = 1.94-5.60), heterozygous codominant model (OR = 2.34, 95% CI = 1.53-3.58), dominant model (OR = 1.79, 95% CI = 1.33-2.41), recessive model (OR = 2.70, 95% CI = 1.73-4.21),and the allelic model (OR = 1.82, 95% CI = 1.41-2.35). All p-values were less than 0.05. Therefore, MTHFR C677T polymorphism has a positive correlation with the risk of H-type hypertension. Among them, TT mutation has the greatest impact on the activity of this enzyme, which causes Hcy to rise and leads to H-type hypertension. CONCLUSION: In summary, our results provide sufficient data to support the hypothesis that the MTHFR C677T polymorphism is related to H-type hypertension susceptibility.


Assuntos
Hipertensão , Metilenotetra-Hidrofolato Redutase (NADPH2) , Povo Asiático , Predisposição Genética para Doença , Humanos , Hipertensão/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único
17.
Phytopathology ; 112(4): 830-841, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34664975

RESUMO

Autophagy is a highly conserved degrading process that is crucial for cell growth and development in eukaryotes, especially when they face starvation and stressful conditions. To evaluate the functions of Atg4 and Atg8 in mycelial growth, asexual and sexual development, and virulence in Cochliobolus heterostrophus, ΔChatg4 and ΔChatg8 mutants were generated by gene replacement. Strains deleted for ChATG4 and ChATG8 genes showed significant changes in vegetative growth and development of conidia and ascospores compared with the wild-type strain. The autophagy process was blocked and virulence was reduced dramatically in ΔChatg4 and ΔChatg8 mutants. In addition, deletion of ChATG4 and ChATG8 disordered Cdc10 subcellular localization and formation of septin rings. The direct physical interaction between ChAtg4 and ChAtg8 was detected by yeast two-hybrid assay, and ChAtg4-GFP was dispersed throughout the cytoplasm, although GFP-ChAtg8 appeared as punctate structures. All phenotypes were restored in complemented strains. Taken together, these findings indicate that ChATG4 and ChATG8 are crucial for autophagy to regulate fungal growth, development, virulence, and localization of septin in C. heterostrophus.


Assuntos
Ascomicetos , Septinas , Ascomicetos/fisiologia , Autofagia , Bipolaris , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Doenças das Plantas/microbiologia , Septinas/genética , Esporos Fúngicos/genética , Virulência/genética
18.
Ann Hum Biol ; 49(1): 27-34, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35254201

RESUMO

BACKGROUND: A body shape index (ABSI) has been proven to be related to a population's CVD incidence. However, the application of this indicator has produced different results. AIM: This study aimed to evaluate the applicability of the ABSI in predicting the incidence of CVD in rural Xinjiang, China, and compare it with waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body mass index (BMI). SUBJECTS AND METHODS: 5375 people aged 18 years or older were included in the study. We used the Cox proportional hazard model to evaluate the relationship between WC, WHR, WHtR, BMI, and ABSI and the incidence of CVD, the area under the curve (AUC) to evaluate the predictive power of each anthropometric index for the incidence of CVD, and restricted cubic splines are used to analyse the trend relationship between anthropometric indicators and the incidence of CVD. RESULTS: After multivariate adjustment, standardised WC, WHR, WHtR, BMI, and ABSI all positively correlated with the incidence of CVD. WC had the highest HR (95% CI) value, 1.64 (1.51-1.78), and AUC (95% CI) value, 0.7743 (0.7537-0.7949). ABSI had the lowest HR (95% CI) value, 1.21(1.10-1.32), and AUC (95% CI) value, 0.7419 (0.7208-0.7630). In the sex-specific sensitivity analysis, the predictive ability of traditional anthropometric indicators for the incidence of CVD is higher than that of ABSI. CONCLUSIONS: In the rural areas of Xinjiang, the traditional anthropometric indicators of WC had better ability to predict the incidence of CVD than ABSI.


Assuntos
Doenças Cardiovasculares , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Fatores de Risco , Circunferência da Cintura , Razão Cintura-Estatura , Relação Cintura-Quadril
19.
Int J Mol Sci ; 23(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35409115

RESUMO

Magnaporthe oryzae is a fungal pathogen that causes rice blast, a highly destructive disease. In the present study, the bacteria strain GS-1 was isolated from the rhizosphere soil of ginseng and identified as Bacillus velezensis through 16S rRNA gene sequencing, whole genome assembly, and average nucleotide identity analysis. B. velezensis strain GS-1 exhibited significant antagonistic activity to several plant fungal pathogens. Through whole genome sequencing, 92 Carbohydrate-Active Enzymes and 13 gene clusters that encoded for secondary metabolites were identified. In addition, strain GS-1 was able to produce the lipopeptide compounds, surfactin, fengycin, and plantazolicin. The inhibitory effects of lipopeptide compounds on M. oryzae were confirmed, and the antagonistic mechanism was explored using transcriptomics and metabolomics analysis. Differential expressed genes (DEGs) and differential accumulated metabolites (DAMs) revealed that the inhibition of M. oryzae by lipopeptide produced by GS-1 downregulated the expression of genes involved in amino acid metabolism, sugar metabolism, oxidative phosphorylation, and autophagy. These results may explain why GS-1 has antagonistic activity to fungal pathogens and revealed the mechanisms underlying the inhibitory effects of lipopeptides produced by GS-1 on fungal growth, which may provide a theoretical basis for the potential application of B. velezensis GS-1 in future plant protection.


Assuntos
Ascomicetos , Magnaporthe , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Ascomicetos/genética , Bacillus , Lipopeptídeos/química , Magnaporthe/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , RNA Ribossômico 16S
20.
Soft Matter ; 17(8): 2205-2214, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33459755

RESUMO

Poly(N-isopropylacrylamide) (pNIPAM) based copolymer microgels were used to create free-standing, transferable, thermoresponsive membranes. The microgels were synthesized by copolymerization of NIPAM with N-benzylhydrylacrylamide (NBHAM). Monolayers of these colloidal gels were subsequently cross-linked using an electron gun leading to the formation of a connected monolayer. Furthermore, the cross-linked microgel layer is detached from the supporting material by dissolving the substrate. These unique systems can be used as transferable, thermoresponsive coatings and as thermoresponsive membranes. As a proof of principle for the use of such membranes we studied the ion transport through them at different temperatures revealing drastic changes when the lower critical solution temperature of the copolymer microgels is reached.

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