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BACKGROUND: While particular strains within the Bacillus species, such as Bacillus subtilis, have been commercially utilised as probiotics, it is critical to implement screening assays and evaluate the safety to identify potential Bacillus probiotic strains before clinical trials. This is because some Bacillus species, including B. cereus and B. anthracis, can produce toxins that are harmful to humans. RESULTS: In this study, we implemented a funnel-shaped approach to isolate and evaluate prospective probiotics from homogenised food waste - sesame oil meal (SOM). Of nine isolated strains with antipathogenic properties, B. subtilis SOM8 displayed the most promising activities against five listed human enteropathogens and was selected for further comprehensive assessment. B. subtilis SOM8 exhibited good tolerance when exposed to adverse stressors including acidity, bile salts, simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and heat treatment. Additionally, B. subtilis SOM8 possesses host-associated benefits such as antioxidant and bile salt hydrolase (BSH) activity. Furthermore, B. subtilis SOM8 contains only haemolysin toxin genes but has been proved to display partial haemolysis in the test and low cytotoxicity in Caco-2 cell models for in vitro evaluation. Moreover, B. subtilis SOM8 intrinsically resists only streptomycin and lacks plasmids or other mobile genetic elements. Bioinformatic analyses also predicted B. subtilis SOM8 encodes various bioactives compound like fengycin and lichendicin that could enable further biomedical applications. CONCLUSIONS: Our comprehensive evaluation revealed the substantial potential of B. subtilis SOM8 as a probiotic for targeting human enteropathogens, attributable to its exceptional performance across selection assays. Furthermore, our safety assessment, encompassing both phenotypic and genotypic analyses, showed B. subtilis SOM8 has a favourable preclinical safety profile, without significant threats to human health. Collectively, these findings highlight the promising prospects of B. subtilis SOM8 as a potent probiotic candidate for additional clinical development.
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Bacillus , Probióticos , Eliminação de Resíduos , Humanos , Bacillus subtilis/genética , Óleo de Gergelim , Células CACO-2 , Estudos Prospectivos , Probióticos/farmacologiaRESUMO
Bone marrow niche cells have been reported to fine-tune hematopoietic stem cell (HSC) stemness via direct interaction or secreted components. Nevertheless, how niche cells control HSC activities remains largely unknown. We previously showed that angiopoietin-like protein 2 (ANGPTL2) can support the ex vivo expansion of HSCs by binding to human leukocyte immunoglobulin-like receptor B2. However, how ANGPTL2 from specific niche cell types regulates HSC activities under physiological conditions is still not clear. Herein, we generated an Angptl2-flox/flox transgenic mouse line and conditionally deleted Angptl2 expression in several niche cells, including Cdh5+ or Tie2+ endothelial cells, Prx1+ mesenchymal stem cells, and Pf4+ megakaryocytes, to evaluate its role in the regulation of HSC fate. Interestingly, we demonstrated that only endothelial cell-derived ANGPTL2 and not ANGPTL2 from other niche cell types plays important roles in supporting repopulation capacity, quiescent status, and niche localization. Mechanistically, ANGPTL2 enhances peroxisome-proliferator-activated receptor D (PPARD) expression to transactivate G0s2 to sustain the perinuclear localization of nucleolin to prevent HSCs from entering the cell cycle. These findings reveal that endothelial cell-derived ANGPTL2 serves as a critical niche component to maintain HSC stemness, which may benefit the understanding of stem cell biology in bone marrow niches and the development of a unique strategy for the ex vivo expansion of HSCs.
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Proteína 2 Semelhante a Angiopoietina/metabolismo , Medula Óssea , Animais , Medula Óssea/metabolismo , Células da Medula Óssea , Células Endoteliais , Células-Tronco Hematopoéticas/metabolismo , Camundongos , Nicho de Células-TroncoRESUMO
There is a growing body of literature on knowledge-guided statistical learning methods for analysis of structured high-dimensional data (such as genomic and transcriptomic data) that can incorporate knowledge of underlying networks derived from functional genomics and functional proteomics. These methods have been shown to improve variable selection and prediction accuracy and yield more interpretable results. However, these methods typically use graphs extracted from existing databases or rely on subject matter expertise, which are known to be incomplete and may contain false edges. To address this gap, we propose a graph-guided Bayesian modeling framework to account for network noise in regression models involving structured high-dimensional predictors. Specifically, we use 2 sources of network information, including the noisy graph extracted from existing databases and the estimated graph from observed predictors in the dataset at hand, to inform the model for the true underlying network via a latent scale modeling framework. This model is coupled with the Bayesian regression model with structured high-dimensional predictors involving an adaptive structured shrinkage prior. We develop an efficient Markov chain Monte Carlo algorithm for posterior sampling. We demonstrate the advantages of our method over existing methods in simulations, and through analyses of a genomics dataset and another proteomics dataset for Alzheimer's disease.
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Doença de Alzheimer , Genômica , Humanos , Teorema de Bayes , Algoritmos , Doença de Alzheimer/genética , Bases de Dados FactuaisRESUMO
The exploration of deep space significantly increases the probability of spacecraft failures due to surface electrostatic discharge, which imposes higher vacuum insulation protection requirements on polyimide (PI), the external insulation material of spacecrafts. To address this challenge, this study proposes using silane coupling agent KH550 for organic grafting treatment of Cr2O3nanoparticles, which are then used to dope and modify PI to enhance the vacuum surface insulation of PI films. The KH550 grafting improves the interface strength between the fillers and the matrix, allowing the fillers to be uniformly dispersed in the matrix. Compared to pure PI films, the prepared PI-Cr2O3@KH550 composite films exhibit significantly enhanced vacuum surface flashover voltage, improved surface/volume resistivity, and dielectric properties. The results demonstrate that PI composite films with 0.8% by mass of Cr2O3@KH550 show the most notable performance improvement, with the DC flashover voltage and impulse flashover voltage in vacuum increasing by 20.7% and 27.8%, respectively. The doping of chromium oxide nanoparticles introduces more deep traps into the PI films and reduce the surface resistivity. The higher deep trap density inhibits charge migration, thereby alleviating secondary electron emission and surface electric field distortion. Simultaneously, the lower surface resistivity facilitates dissipating surface charges and improves the surface insulation. These findings are of significant reference value for promoting the enhancement of aerospace insulation performance.
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OBJECTIVE: Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of plasminogen activator. The functional 4G/5G polymorphism of the gene coding for PAI-1 may affect PAI-1 plasmatic activity, influencing the imbalance between coagulation and fibrinolysis cascades. In this study, we investigated the association between the PAI-1 4G/5G genotype and the development and residual thrombus of acute primary mesenteric venous thrombosis (MVT). METHODS: The clinical data of 34 patients who underwent acute primary MVT were retrospectively reviewed. Fluorescence in situ hybridization was used to determine if patients had the 4G/5G polymorphism in the promoter of the PAI-1 gene. Patients were stratified according to the genotype of PAI-1. RESULTS: 11 patients (32.3%) were homozygous for the 4G genotype, 23 patients (67.6%) were non-homozygous for the 4G genotype (5G/5G). The extent of thrombosis was not correlated with the PAI-4G/5G polymorphism. After a mean follow-up of 16.6 ± 10.4 months, the 4G/4G genotype had a significantly larger thrombus burden (p < 0.05). 54% of patients in the 4G/4G genotype group had no lessening in the degree of mesenteric venous thrombosis, significantly higher than other patients (4G/5G + 5G/5G genotypes) (p < 0.05). CONCLUSION: The PAI-1 4G/4G predicts residual thrombus of mesenteric veins after the acute phase.
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Genótipo , Inibidor 1 de Ativador de Plasminogênio , Trombose Venosa , Humanos , Inibidor 1 de Ativador de Plasminogênio/genética , Masculino , Feminino , Trombose Venosa/genética , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Veias Mesentéricas , Idoso , Polimorfismo Genético , Doença Aguda , Regiões Promotoras Genéticas/genética , Predisposição Genética para DoençaRESUMO
4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75.0 and 37.5 g ai/ha, which is comparable to the control herbicide mesotrione. Moreover, compound G31 showed excellent crop safety, with less than or equal to 10% injury rates to corn, sorghum, soybean and cotton at a dosage of 225 g ai/ha. Molecular docking and molecular dynamics simulation analysis revealed that the compound G31 could stably bind to Arabidopsis thaliana HPPD (AtHPPD). This study indicated that the compound G31 could be used as a lead molecular structure for the development of novel HPPD inhibitors, which provided an idea for the design of new herbicides with unique molecular scaffold.
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To address the urgent need for new antifungal agents, a collection of novel pyrazole carboxamide derivatives incorporating a benzimidazole group were innovatively designed, synthesized, and evaluated for their efficacy against fungal pathogens. The bioassay results revealed that the EC50 values for the compounds A7 (3-(difluoromethyl)-1-methyl-N-(1-propyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxamide) and B11 (N-(1-(4-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide) against B. cinerea were notably low to 0.79 µg/mL and 0.56 µg/mL, respectively, demonstrating the potency comparable to that of the control fungicide boscalid, which has an EC50 value of 0.60 µg/mL. Noteworthy is the fact that in vivo tests demonstrated that A7 and B11 showed superior protective effects on tomatoes and strawberries against B. cinerea infection when juxtaposed with the commercial fungicide carbendazim. The examination through scanning electron microscopy revealed that B11 notably alters the morphology of the fungal mycelium, inducing shrinkage and roughening of the hyphal surfaces. To elucidate the mechanism of action, the study on molecular docking and molecular dynamics simulations was conducted, which suggested that B11 effectively interacts with crucial amino acid residues within the active site of succinate dehydrogenase (SDH). This investigation contributes a novel perspective for the structural design and diversification of potential SDH inhibitors, offering a promising avenue for the development of antifungal therapeutics.
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BACKGROUND: Mycobacterium abscessus is a new pathogen in recent years, which belongs to non-tuberculosis mycobacterium. Mycobacterium abscessus is widely involved in many nosocomial infections and secondary aggravation of genetic respiratory diseases. Mycobacterium abscessus is naturally resistant to most antibiotics and is difficult to treat. We report a case of mycobacterium abscessus infection with hemoptysis as the first manifestation. METHODS: Bronchoscopy, next-generation sequencing (NGS). RESULTS: Acid-fast staining of bronchoscopic lavage fluid showed that a small amount of acid-fast bacilli could be seen. NGS test showed the presence of Mycobacterium abscess, sequence number 137 (reference range ≥ 0), and symptomatic treatment against non-tuberculosis mycobacteria. CONCLUSIONS: For the follow-up infection of patients with hemoptysis, the treatment effect of antibiotics is not good, so the pathological tissue should be obtained by bronchoscopy or percutaneous lung biopsy in time, and the diagnosis should be confirmed by NGS if necessary.
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Broncoscopia , Hemoptise , Infecções por Mycobacterium não Tuberculosas , Humanos , Hemoptise/diagnóstico , Hemoptise/etiologia , Hemoptise/microbiologia , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Masculino , Mycobacterium abscessus/isolamento & purificação , Mycobacterium abscessus/genética , Sequenciamento de Nucleotídeos em Larga Escala , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Líquido da Lavagem Broncoalveolar/microbiologia , FemininoRESUMO
BACKGROUND: The primary goal of this research is to delve into the clinical and pathological facets of the left-sided inferior vena cava (IVC), and to catalog and condense its radiological and clinical attributes, thereby furnishing valuable references for pertinent clinical diagnosis and therapeutic procedures. METHODS: We collated and scrutinized the general clinical features, radiological characteristics, and diagnostic and therapeutic strategies of 30 patients diagnosed with left-sided IVC (LIVC) in our hospital from July 2014 through February 2024. RESULTS: A majority of patients were asymptomatic and were only identified during diagnostic procedures for other ailments. CT scans revealed anomalies in the anatomical configuration of the LIVC. The radiological presentations primarily showcased the right common iliac vein traversing the lumbar vertebrae to amalgamate with the left common iliac vein, forming the IVC. The IVC ascended on the left side of the abdominal aorta, accepted the left renal vein, and then transitioned to the right side of the abdominal aorta. In 3 instances, the IVC was witnessed ascending on the left side of the abdominal aorta, permeating through the diaphragm, converging with the azygos vein and abdominal aorta, and making its way into the right atrium. In these cases, the hepatic segment of the IVC was missing, and there was an absence of the IVC inferior to the hepatic vein, a condition we refer to as complete LIVC. CONCLUSIONS: LIVC is predominantly asymptomatic but carries significant anatomical implications during abdominal, retroperitoneal surgeries, and vascular interventions. Precise identification and management of this anomaly can mitigate surgical risks and enhance patient prognosis.
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Six previously undescribed prenylated C6-C3 derivatives (1-6) were isolated from the root of Illicium ternstroemioides A. C. Smith. Their structures were elucidated based on extensive spectroscopic analyses (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of 1-3 were determined using electronic circular dichroism (ECD), and Mo2(OAc)4 induced circular dichroism (ICD). Compound 3 exhibited weak activity against Coxsackievirus B3 with an IC50 value of 33.3 µM, and compound 5 exhibited more potent activity against Coxsackievirus B3 with an IC50 value of 6.4 µM.
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Illicium , Illicium/química , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Dicroísmo Circular , Antivirais/farmacologiaRESUMO
Three new prenylated C6-C3 compounds (1-3), together with two known prenylated C6-C3 compounds (4-5) and one known C6-C3 derivative (6), were isolated from the roots of Illicium brevistylum A. C. Smith. The structures of 1-3 were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, CD experiments and ECD calculations. The structure of illibrefunone A (1) was confirmed by single-crystal X-ray diffraction analysis. All compounds were evaluated in terms of their anti-inflammatory potential on nitric oxide (NO) generation in lipopolysaccharide-stimulated murine RAW264.7 macrophages and murine BV2 microglial cells, antiviral activity against Coxsackievirus B3 (CVB3) and influenza virus A/Hanfang/359/95 (H3N2). Compounds 3 and 4 exhibited potent inhibitory effects on the production of NO in RAW 264.7 cells with IC50 values of 20.57 and 12.87 µM respectively, which were greater than those of dexamethasone (positive control). Compounds 1 and 4-6 exhibited weak activity against Coxsackievirus B3, with IC50 values ranging from 25.87 to 33.33 µM.
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Antivirais , Illicium , Vírus da Influenza A Subtipo H3N2 , Óxido Nítrico , Raízes de Plantas , Animais , Camundongos , Raízes de Plantas/química , Óxido Nítrico/biossíntese , Óxido Nítrico/antagonistas & inibidores , Estrutura Molecular , Antivirais/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Células RAW 264.7 , Illicium/química , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Macrófagos/efeitos dos fármacos , Enterovirus Humano B/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , PrenilaçãoRESUMO
Three new cadinane sesquiterpenes (1-3) and three known sesquiterpenes were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith. The structures of the new compounds were elucidated by extensive analysis of spectroscopic and HRESIMS data. The structures of illiternins A-C (1-3) were confirmed by single crystal X-ray diffraction, allowing for the determination of their absolute configurations. Compounds 3 and 6 exhibited antiviral activity against Coxsackievirus B3 with IC50 values of 33.3 and 57.7 µM, respectively.
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Illicium , Sesquiterpenos , Illicium/química , Estrutura Molecular , Sesquiterpenos Policíclicos , Sesquiterpenos/químicaRESUMO
BACKGROUND: Although there are many reasons for extubation failure, maintaining negative or lower positive fluid balances 24 hours before extubation may be a key measure for successful extubation. AIM: To assess the predictive value of fluid balance before extubation and its outcome in mechanically ventilated cases in the intensive care unit (ICU). STUDY DESIGN: This retrospective cohort study involved collecting clinical data from patients undergoing mechanical ventilation in Lanzhou general adult ICU from January 2022 to December 2022. Based on extubation outcomes, the patients were divided into a successful extubation group and a failed extubation group. Their fluid balance levels 24 h before extubation were compared with analyse the predictive value of fluid balance on extubation outcomes in patients undergoing mechanical ventilation. RESULTS: In this study, clinical data from 545 patients admitted to a general adult ICU were collected. According to the inclusion and exclusion criteria, 265 (48.6%) patients were included, of which 197 (74.3%) were successfully extubated; extubation was unsuccessful in 68 (25.7%) patients. The total intake and fluid balance levels in patients in the failed extubation group 24 h before extubation were significantly higher than those in the successful extubation group, with a median of 2679.00 (2410.44-3193.50) mL versus 2435.40 (1805.04-2957.00) mL, 831.50 (26.25-1407.94) mL versus 346.00 (-163.00-941.50) mL. Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off value for predicting extubation outcomes was 497.5 mL (sensitivity 64.7%, specificity 59.4%) for fluid balance 24 h before extubation. The area under the ROC curve was 0.627 (95% confidence interval [CI] 0.547-0.707). Based on the logistic regression model, cumulative fluid balance >497.5 mL 24 h before extubation could predict its outcomes in mechanically ventilated patients in the ICU (OR = 5.591, 95% CI [2.402-13.015], p < .05). CONCLUSIONS: The fluid balance level 24 h before extubation was correlated with the outcome of extubation in mechanically ventilated patients in the ICU. The risk of extubation failure was higher when the fluid balance level was >497.5 mL. RELEVANCE TO CLINICAL PRACTICE: Tracheal intubation is a crucial life support technique for many critically ill patients, and determining the appropriate time for extubation remains a challenge for clinicians. Although there are many reasons for extubation failure, acute pulmonary oedema caused by continuous positive fluid balance and volume overload is one of the main reasons for extubation failure. Therefore, it is very important to study the relationship between fluid balance and extubation outcome to improve the prognosis of patients with invasive mechanical ventilation in ICU.
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Extubação , Unidades de Terapia Intensiva , Respiração Artificial , Desmame do Respirador , Equilíbrio Hidroeletrolítico , Humanos , Estudos Retrospectivos , Feminino , Masculino , Equilíbrio Hidroeletrolítico/fisiologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Idoso , China , AdultoRESUMO
Sesquiterpene synthases (STPSs) catalyze carbocation-driven cyclization reactions that can generate structurally diverse hydrocarbons. The deprotonation-reprotonation process is widely used in STPSs to promote structural diversity, largely attributable to the distinct regio/stereoselective reprotonations. However, the molecular basis for reprotonation regioselectivity remains largely understudied. Herein, we analyzed two highly paralogous STPSs, Artabotrys hexapetalus (-)-cyperene synthase (AhCS) and ishwarane synthase (AhIS), which catalyze reactions that are distinct from the regioselective protonation of germacrene A (GA), resulting in distinct skeletons of 5/5/6 tricyclic (-)-cyperene and 6/6/5/3 tetracyclic ishwarane, respectively. Isotopic labeling experiments demonstrated that these protonations occur at C3 and C6 of GA in AhCS and AhIS, respectively. The cryo-electron microscopy-derived AhCS complex structure provided the structural basis for identifying different key active site residues that may govern their functional disparity. The structure-guided mutagenesis of these residues resulted in successful functional interconversion between AhCS and AhIS, thus targeting the three active site residues [L311-S419-C458]/[M311-V419-A458] that may act as a C3/C6 reprotonation switch for GA. These findings facilitate the rational design or directed evolution of STPSs with structurally diverse skeletons.
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Alquil e Aril Transferases , Sesquiterpenos , Microscopia Crioeletrônica , Sesquiterpenos/química , Catálise , Domínio Catalítico , Alquil e Aril Transferases/genéticaRESUMO
BACKGROUND: Microspore culture is one of the important biotechnological tools in plant breeding. The induction of microspore embryogenesis is a critical factor that affects the yield of microspore-derived embryo productions. Cold treatment has been reported to reprogram the gametophytic pathway in various plant species. However, the exact mechanism(s) underlying the effect of cold pre-treatment of floral buds on the efficiency of ME is still not clear. RESULTS: In this study, the effects of cold stress on the microspore totipotency of rice cultivar Zhonghua 11 were investigated. Our results revealed that a 10-day cold treatment is necessary for microspore embryogenesis initiation. During this period, the survival rate of microspores increased and reached a peak at 7 days post treatment (dpt), before decreasing at 10 dpt. RNA-seq analysis showed that the number of DEGs increased from 3 dpt to 10 dpt, with more downregulated DEGs than upregulated ones at the same time point. GO enrichment analysis showed a shift from 'Response to abiotic stimulus' at 3 dpt to 'Metabolic process' at 7 and 10 dpt, with the most significant category in the cellular component being 'cell wall'. KEGG analysis of the pathways revealed changes during cold treatment. Mass spectrometry was used to evaluate the variations in metabolites at 10 dpt compared to 0 dpt, with more downregulated DEMs being determined in both GC-MS and LC-MS modes. These DEMs were classified into 11 categories, Most of the DEMs belonged to 'lipids and lipid-like molecules'. KEGG analysis of DEMs indicates pathways related to amino acid and nucleotide metabolism being upregulated and those related to carbohydrate metabolism being downregulated. An integration analysis of transcriptomics and metabolomics showed that most pathways belonged to 'Amino acid metabolism' and 'Carbohydrate metabolism'. Four DEMs were identified in the interaction network, with stearidonic acid involving in the most correlations, suggesting the potential role in microspore totipotency. CONCLUSIONS: Our findings exhibited the molecular events occurring during stress-induced rice microspore. Pathways related to 'Amino acid metabolism' and 'Carbohydrate metabolism' may play important roles in rice microspore totipotency. Stearidonic acid was identified, which may participate in the initiation of microspore embryogenesis.
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Resposta ao Choque Frio , Oryza , Transcriptoma , Oryza/genética , Melhoramento Vegetal , AminoácidosRESUMO
Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses. Plasma was collected from InV pre-vaccinated Omicron-infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay. InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3-fold and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35 112 and 28 186 during 11-22 DPI, about 2.6-fold and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-fold, 5.6-fold, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs. InV and Ad5-nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.
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Infecções Irruptivas , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Imunoglobulina G , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
BACKGROUND: The pathogenicity and virulence of the Omicron strain have weakened significantly pathogenesis of Omicron variants. Accumulating data indicated accessory proteins play crucial roles in host immune evasion and virus pathogenesis of SARS-CoV-2. Therefore, the impact of simultaneous deletion of accessory protein ORF7a, ORF7b and ORF8 on the clinical characteristics and specific immunity in Omicron breakthrough infected patients (BIPs) need to be verified. METHODS: Herein, plasma cytokines were identified using a commercial Multi-cytokine detection kit. Enzyme-linked immunosorbent assay and pseudovirus neutralization assays were utilized to determine the titers of SARS-CoV-2 specific binding antibodies and neutralizing antibodies, respectively. In addition, an enzyme-linked immunospot assay was used to quantify SARS-CoV-2 specific T cells and memory B cells. RESULTS: A local COVID-19 outbreak was caused by the Omicron BA.2 variant, which featured a deletion of 871 base pairs (∆871 BA.2), resulting in the removal of ORF7a, ORF7b, and ORF8. We found that hospitalized patients with ∆871 BA.2 had significantly shorter hospital stays than those with wild-type (WT) BA.2. Plasma cytokine levels in both ∆871 BA.2 and WT BA.2 patients were within the normal range of reference, and there was no notable difference in the titers of SARS-CoV-2 ancestor or Omicron-specific binding IgG antibodies, neutralizing antibody titers, effector T cells, and memory B cells frequencies between ∆871 BA.2 and WT BA.2 infected adult patients. However, antibody titers in ∆871 BA.2 infected adolescents were higher than in adults. CONCLUSIONS: The simultaneous deletion of ORF7a, ORF7b, and ORF8 facilitates the rapid clearance of the BA.2 variant, without impacting cytokine levels or affecting SARS-CoV-2 specific humoral and cellular immunity in Omicron-infected individuals.
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COVID-19 , Adolescente , Adulto , Humanos , SARS-CoV-2/genética , Anticorpos Neutralizantes , Anticorpos Antivirais , Citocinas , ELISPOTRESUMO
A successful deception involves making a decision, acting on it, and evaluating results. Here, we investigated deception in a non-clinical sample (n = 36) with varying autism traits using a coin-toss paradigm of active deception. The subjects were asked to react to the instructions by clicking one of the two boxes that could mislead their opponents, followed by feedback on their success or failure. During this reaction, their EEG activity was recorded, and the results suggested that people with high autistic traits exhibited longer reaction times and lower amplitude of P3 in the decision-making stage compared to individuals with low autistic traits. The feedback evaluation stage in the high autistic trait group elicited lower amplitude of FRN and P3. Overall, these results indicated that people with high autistic traits experienced difficulties in deceiving, which could be related to atypical neural mechanisms.
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Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Tempo de Reação , EnganaçãoRESUMO
Chemical investigation of an alcohol extract from the twigs and leaves of Illicium henryi Diels resulted in the isolation of two new acorane-related seco-sesquiterpenes (1 and 3), two new acorane-related seco-norsesquiterpenes (2 and 4), one new 2-epi-cedrane sesquiterpene (5), eight new acorane-type sesquiterpenes (6-13), and a known major constituent of acorenone B (14). Their structures were established by interpreting extensive spectroscopic data, including HRESIMS, NMR (1H and 13C NMR, 1H-1H COSY, HSQC, and HMBC), and NOE difference spectra analysis. The absolute configurations of 1, 2, 4-7, 9, 10, and 14 were determined by X-ray crystallography, while chemical transformation methods were performed with compound 14 as the starting material to elegantly solve the absolute configuration issue of compounds 8 and 11-13. Notably, 1 and 2 are seco-sesquiterpenes that are related to acorane and possess an unusual ketal-linked hemiacetal in a 6,8-dioxabicyclo[3.2.1]octan-7-ol scaffold ring system. Plausible biosynthetic pathways for compounds 1-14, which were derived from the acorane skeleton, were proposed. All the isolated compounds (1-14) were evaluated for their antiviral and cytotoxic activities.
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Antivirais , Illicium , Sesquiterpenos , Antivirais/química , Antivirais/farmacologia , Illicium/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Folhas de Planta/química , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Two-dimensional conductive metal-organic frameworks (2D-c-MOFs) have attracted extensive attention owing to their unique structures and physical-chemical properties. However, the planarly extended structure of 2D-c-MOFs usually limited the accessibility of the active sites. Herein, we designed a triptycene-based 2D vertically conductive MOF (2D-vc-MOF) by coordinating 2,3,6,7,14,15-hexahydroxyltriptycene (HHTC) with Cu2+ . The vertically extended 2D-vc-MOF(Cu) possesses a weak interlayer interaction, which leads to a facile exfoliation to the nanosheet. Compared with the classical 2D-c-MOFs with planarly extended 2D structures, 2D-vc-MOF(Cu) exhibits a 100 % increased catalytic activity in terms of turnover number and a two-fold increased selectivity. Density functional theory (DFT) calculations further revealed that higher activity originated from the lower energy barriers of the vertically extended 2D structures during the CO2 reduction reaction process.