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Shaping hard and brittle materials, e.g. cermets, at micrometer resolution has long been known challenging for both mechanical machining and high energy beam based additive manufacturing. Digital light processing (DLP), which features great printing quality and decent precision, unfortunately lacks capability to deal with the popular slurry-typed cermet precursor due to the tremendous optical absorption by its particles. Here, an innovative protocol based on a versatile collapsable matrix is devised to allow high-precision printing of WC-Co cermets on DLP platform. By tuning the external environment, this matrix attenuates composite powders to facilitate photopolymerization at the printing stage, and shrinks to condense green parts prior to thermal sintering. The as-obtained samples by collapsable matrix assisted DLP can reach a relative density of ≈90%, a record-breaking resolution of ≈10 µm, and a microhardness of up to 14.5 GPa. Complex delicate structures, including school emblem, honeycomb, and micro-drill can be directly fabricated, which has never been achieved before. Impressively, the as-obtained micro-drill is able to be directly used in drilling tasks. The above strategy represents a great progress in DLP by enabling shaping strong light attenuating materials at high resolution. Such advantages are ideal for the next generation ceramic-metal composite additive manufacturing.
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OBJECTIVE: The early response to concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) is closely correlated with prognosis. In this study, we aimed to predict early response using a combined model that combines sub-regional radiomics features from multi-sequence MRI with clinically relevant factors. METHODS: A total of 104 patients with LA-NPC were randomly divided into training and test cohorts at a ratio of 3:1. Radiomic features were extracted from subregions within the tumor area using the K-means clustering method, and feature selection was performed using LASSO regression. Four models were established: a radiomics model, a clinical model, an Intratumor Heterogeneity (ITH) score-based model and a combined model that integrates the ITH score with clinical factors. The predictive performance of these models was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Among the models, the combined model incorporating the ITH score and clinical factors exhibited the highest predictive performance in the test cohort (AUC=0.838). Additionally, the models based on ITH score showed superior prognostic value in both the training cohort (AUC=0.888) and the test cohort (AUC=0.833). CONCLUSION: The combined model that integrates the ITH score with clinical factors exhibited superior performance in predicting early response following concurrent chemoradiotherapy in patients with LA-NPC.
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OBJECTIVE: The objective of this study was to investigate the activity and connectivity of cerebral and cerebellar cortices underlying the sensory trick (ST) effects in patients with cervical dystonia (CD), using electroencephalography (EEG). METHODS: We recruited 15 CD patients who exhibited clinically effective ST and 15 healthy controls (HCs) who mimicked the ST maneuver. EEG signals and multiple-channel electromyography (EMG) were recorded simultaneously during resting and acting stages. EEG source analysis and functional connectivity were performed. To account for the effects of sensory processing, we calculated relative power changes as the difference in power spectral density between resting and the maneuver execution. RESULTS: ST induced a decrease in low gamma (30-50 Hz) spectral power in the primary sensory and cerebellar cortices, which remained lower than in HCs during the maintenance period. Compared with HCs, patients exhibited consistently strengthened connectivity within the sensorimotor network during the maintenance period, particularly in the primary sensory-sensorimotor cerebellum connection. INTERPRETATION: The application of ST resulted in altered cortical excitability and functional connectivity regulated by gamma oscillation in CD patients, suggesting that this effect cannot be solely attributed to motor components. The cerebellum may play important roles in mediating the ST effects.
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Erythritol is a natural non-caloric sweetener, which is produced by fermentation and extensively applied in food, medicine and chemical industries. The final step of the erythritol synthesis pathway is involved in erythritol reductase, whose activity and NADPH-dependent become the limiting node of erythritol production efficiency. Herein, we implemented a strategy combining molecular docking and thermal stability screening to construct an ER mutant library. And we successfully obtained a double mutant ERK26N/V295M (ER*) whose catalytic activity was 1.48 times that of wild-type ER. Through structural analysis and MD analysis, we found that the catalytic pocket and the enzyme stability of ER* were both improved. We overexpressed ER* in the engineered strain ΔKU70 to obtain the strain YLE-1. YLE-1 can produce 39.47 g/L of erythritol within 144 h, representing a 35% increase compared to the unmodified strain, and a 10% increase compared to the strain overexpressing wild-type ER. Considering the essentiality of NADPH supply, we further co-expressed ER* with two genes from the oxidative phase of PPP, ZWF1 and GND1. This resulted in the construction of YLE-3, which exhibited a significant increase in production, producing 47.85 g/L of erythritol within 144 h, representing a 63.90% increase compared to the original chassis strain. The productivity and the yield of the engineered strain YLE-3 were 0.33 g/L/h and 0.48 g/g glycerol, respectively. This work provided an ER mutation with excellent performance, and also proved the importance of cofactors in the process of erythritol synthesis, which will promote the industrial production of erythritol by metabolic engineering of Y. lipolytica.
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OBJECTIVE: The purpose of this study was to compare the image quality of different MRI sequences regarding the presentation of Dermatofibrosarcoma Protuberans (DFSP). MATERIALS AND METHODS: We retrospectively collected MRI images of 40 patients who had been pathologically diagnosed with DFSP, including 21 primary tumors and 19 recurrent tumors. The image quality of different MRI sequences was assessed subjectively by two radiologists, taking into account the display of the lesions, artifacts, and distortions, as well as the overall impact of the image quality. RESULTS: Among the 40 cases, 22 cases involved the trunk, 14 cases involved the shoulders and limbs, 2 cases involved the head and neck, 1 case involved the breast, and 1 case involved the groin. In terms of image quality, fat suppression T2-weighted images were superior to T1-weighted images and T2-weighted images (P<0.05). The difference between fat suppression T2-weighted images and contrast-enhanced images was not significant (P>0.05). As far as lesion contrast is concerned, diffusion-weighted images, fat suppression T2-weighted images, and contrast-enhanced images did not differ significantly (P>0.05). On the DWI images, there were severe magnetic artifacts and deformations. CONCLUSIONS: Fat suppression T2-weighted images and enhanced sequences produce the highest quality images, while diffusion-weighted images provide the best lesion contrast.
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Anoplophora glabripennis is a critical global quarantine pest. Recently, its distribution has been extended to colder and higher-latitude regions. The adaptation to low temperatures is vital for the successful colonization of insects in new environments. However, the metabolic pathways of A. glabripennis larvae under cold stress remain undefined. This study analyzed the larval hemolymph under different low-temperature treatments using LC-MS/MS. The results showed that differential metabolites associated with sugar and lipid metabolism are pivotal in the larval chill coma process. Under low-temperature treatments, the glycerol content increased significantly compared with the control group. Cold stress significantly induced the expression of AglaGK2 and AglaGPDHs. After undergoing RNAi treatment for 48 h, larvae exposed to -20 °C for 1 h showed reduced recovery when injected with ds-AglaGK2 and ds-AglaGPDH1 compared to the control group, indicating that glycerol biosynthesis plays a role in the low-temperature adaptation of A. glabripennis larvae. Our results provide a theoretical basis for clarifying the molecular mechanism of A. glabripennis larvae in response to environmental stresses.
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Temperatura Baixa , Glicerol , Proteínas de Insetos , Larva , Animais , Larva/metabolismo , Larva/crescimento & desenvolvimento , Glicerol/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Adaptação Fisiológica , Espectrometria de Massas em Tandem , Hemolinfa/metabolismo , Hemolinfa/química , BesourosRESUMO
Pyrolysis is an effective process for disposing of municipal sewage sludge (SS). Plastics can affect the SS pyrolysis behaviour and pyrolysis products due to their low ash and high hydrocarbon ratio. The secondary pollutants from the pyrolysis process may also be affected. Therefore, polyethylene terephthalate (PET), a typical plastic, was chosen to investigate the release characteristics of pollutants containing nitrogen, sulphur, and chlorine via SS pyrolysis, and the changes of biochar to adsorb two typical heavy metals, Pb and Cu. The pyrolysis of PET plastics facilitates the migration of N toward solid and liquid-phase products, S and Cl to the gas-phase products via pyrolysis. Oxygenated compounds of pyrolytic volatiles decreased from 38.18% to 28.43%, concurrently promoting the formation of phenolic compounds. The co-pyrolysis improved the quality of biochar and the ability to adsorb Pb and Cu. This systematic study can provide some support for the further improvement of SS pyrolysis technology, and will also be beneficial for subsequent applications.
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Laccase mediators possess advantage of oxidizing substrates with high redox potentials, such as aflatoxin B1 (AFB1). High costs of chemically synthesized mediators limit laccase industrial application. In this study, thin stillage extract (TSE), a byproduct of corn-based ethanol fermentation was investigated as the potential natural mediator of laccases. Ferulic acid, p-coumaric acid, and vanillic acid were identified as the predominant phenolic compounds of TSE. With the assistance of 0.05 mM TSE, AFB1 degradation activity of novel laccase Glac1 increased by 17 times. The promoting efficiency of TSE was similar to ferulic acid, but superior to vanillic acid and p-coumaric acid, with 1.2- and 1.3-fold increases, respectively. After Glac1-TSE treatment, two oxidation products were identified. Ames test showed AFB1 degradation products lost mutagenicity. Meanwhile, TSE also showed 1.3-3.0 times promoting effect on laccase degradation activity in cereal flours. Collectively, a safe and highly efficient natural mediator was obtained for aflatoxin detoxification.
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Lacase , Zea mays , Lacase/metabolismo , Lacase/química , Zea mays/química , Zea mays/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Aflatoxina B1/química , Aflatoxina B1/metabolismo , Oxirredução , Extratos Vegetais/química , Fermentação , Ácidos Cumáricos/química , Ácidos Cumáricos/metabolismoRESUMO
The detection of the amount of aflatoxin M1 (AFM1) in milk is crucial for food safety. Here, we utilize a fiber optic (FO) localized surface plasmon resonance (LSPR) biosensor by constructing gold nanoparticle (AuNP) multimers, in which the nanogaps amplified the LSPR signal by the hot spot effect, and achieved a highly sensitive detection of f AFM1. Through the optimization of parameter conditions for the fabrication of the sensor and detection system, a high performance result from the FO LSPR biosensor was obtained, and the method for AFM1 detection was established, with a wide detection range of 0.05-100 ng/mL and a low limit of detection (LOD) of 0.04 ng/mL, and it has been successfully validated with the actual sample milk. Therefore, it is a good strategy to fabricate highly sensitive FO LSPR sensors for detecting AFM1 by constructing AuNP multimers, and this approach is suitable for developing other biosensors.
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OBJECTIVES: Acute pancreatitis(AP) is a common digestive tract disease, often accompanied by severe metabolic disorders, but there are no specific markers and treatment methods, and the potential metabolic pathways behind it remain to be explored. METHODS: Establish mild acute pancreatitis and severe acute pancreatitis models in rats and intervene with antioxidant NAC. Analyze serum oxidative stress indicators and pathological changes in pancreatic tissue. In addition, non-targeted metabolomics analysis of serum differential metabolites between groups was conducted based on the LC/MS system. RESULTS: The pathological score of the model group rats increased, and the levels of oxidative stress factors ROS and MDA significantly increased, while the activity of the antioxidant enzyme SOD decreased. After NAC intervention, oxidative stress damage in rats was alleviated. Non-targeted metabolomics experiments suggest significant differences in serum metabolic profiles among different groups of rats. CONCLUSION: Metabolomics results show that the obtained differential metabolites are expected to become serum biomarkers for AP.
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OBJECTIVE: To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma. METHODS: In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously. RESULTS: In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01). CONCLUSIONS: Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.
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Previous studies have shown that polymethoxylated flavonoids-loaded citral emulsion (PCT) can inhibit the growth and reproduction of Penicillium in citrus; however, PCT is difficult to apply to fruit preservation due to its high fluidity and volatility. Therefore, in this study, we combined PCT with chitosan (CS) to investigate the effect of a composite coating on citrus preservation. The results showed that compared to the control group, the CS-PCT group could effectively reduce the decay rate and maintain moisture availability, color difference, and hardness. Moreover, the contents of nonenzymatic antioxidants and volatile substances with antimicrobial activity were better preserved. In addition, the activities of related antioxidant enzymes were greater in the treatment group, and the expression of the corresponding enzyme-encoding genes was upregulated. Consequently, CS-PCT treatment could effectively maintain fruit quality and improve the resistance of citrus fruits during storage; moreover, it can be considered a nontoxic and efficient citrus preservative.
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The current standard treatment for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) comprises concurrent radiotherapy (CRT) alongside platinum-based chemotherapy. However, innovative therapeutic alternatives are being evaluated in phase II/III randomized trials. This study employed a Bayesian network meta-analysis (NMA) using fixed effects to provide both direct and indirect comparisons of all existing treatment modalities for unresectable LASCCHN. METHODS: We referenced randomized controlled trials (RCTs) from January 2000 to July 2023 by extensively reviewing PubMed, EMBASE, and Web of Science databases, adhering to the Cochrane methodology. Relevant data, including summary estimates of overall survival (OS) and progression-free survival (PFS), were extracted from these selected studies and recorded in a predefined database sheet. Subsequently, we conducted a random effects network meta-analysis using a Bayesian framework. RESULTS: Based on the Surface Under the Cumulative Ranking (SUCRA) values, the league table organizes the various treatments for OS in the following order: IC + RT&MTT, MTT-CRT, IC + CRT&MTT, CRT, IC + CRT, MTT-RT, IC + MTT-RT, and RT. In a similar order, the treatments rank as follows according to the league table: IC + CRT&MTT, MTT-CRT, IC + CRT, IC + RT&MTT, CRT, IC + MTT-RT, MTT-RT, and RT. Notably, none of these treatments showed significant advantages over concurrent chemoradiotherapy. CONCLUSION: Despite concurrent chemoradiotherapy being the prevailing treatment for LASCCHN, our findings suggest the potential for improved outcomes when concurrent chemoradiotherapy is combined with targeted therapy or induction chemotherapy.
The current standard treatment for advanced head and neck cancer involves combining radiation therapy with chemotherapy. However, there are ongoing trials exploring alternative therapies. In this study, we conducted a comprehensive analysis of existing treatments using a statistical method called network meta-analysis. Our analysis included data from randomized controlled trials published between January 2000 and July 2023. We focused on overall survival and progression-free survival as key outcome measures. The results of our analysis showed that none of the alternative treatments demonstrated significant advantages over the standard concurrent chemoradiotherapy. Nevertheless, there is potential for improved outcomes when targeted therapy or induction chemotherapy is combined with concurrent chemoradiotherapy.
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Neoplasias de Cabeça e Pescoço , Metanálise em Rede , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Quimiorradioterapia/métodos , Teorema de Bayes , Ensaios Clínicos Controlados Aleatórios como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Flavonoids are a diverse family of natural compounds that are widely distributed in plants and play a critical role in plant growth, development, and stress adaptation. In recent years, the biosynthesis of flavonoids in plants has been well-researched, with the successive discovery of key genes driving this process. However, the regulation of flavonoid biosynthesis in fungi remains unclear. Stropharia rugosoannulata is an edible mushroom known for its high nutritional and pharmacological value, with flavonoids being one of its main active components. To investigate the flavonoid content of S. rugosoannulata, a study was conducted to extract and determine the total flavonoids at four stages: young mushroom (Ym), gill (Gi), maturation (Ma), and parachute-opening (Po). The findings revealed a gradual increase in total flavonoid concentration as the fruiting body developed, with significant variations observed between the Ym, Gi, and Ma stages. Subsequently, we used UPLC-MS/MS and transcriptome sequencing (RNA-seq) to quantify the flavonoids and identify regulatory genes of Ym, Gi, and Ma. In total, 53 flavonoid-related metabolites and 6726 differentially expressed genes (DEGs) were identified. Through KEGG pathway enrichment analysis, we identified 59 structural genes encoding flavonoid biosynthesis-related enzymes, most of which were up-regulated during the development of the fruiting body, consistent with the accumulation of flavonoids. This research led to the establishment of a comprehensive transcriptional metabolic regulatory network encompassing flavonoids, flavonoid synthases, and transcription factors (TFs). This represents the first systematic exploration of the molecular mechanism of flavonoids in the fruiting of fungi, offering a foundation for further research on flavonoid mechanisms and the breeding of high-quality S. rugosoannulata.
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Over recent decades, electroencephalogram (EEG) has become an essential tool in the field of clinical analysis and neurological disease research. However, EEG recordings are notably vulnerable to artifacts during acquisition, especially in clinical settings, which can significantly impede the accurate interpretation of neuronal activity. Blind source separation is currently the most popular method for EEG denoising, but most of the sources it separates often contain both artifacts and brain activity, which may lead to substantial information loss if handled improperly. In this paper, we introduce a dual-threshold denoising method combining spatial filtering with frequency-domain filtering to automatically eliminate electrooculogram (EOG) and electromyogram (EMG) artifacts from multi-channel EEG. The proposed method employs a fusion of second-order blind identification (SOBI) and canonical correlation analysis (CCA) to enhance source separation quality, followed by adaptive threshold to localize the artifact sources, and strict fixed threshold to remove strong artifact sources. Stationary wavelet transform (SWT) is utilized to decompose the weak artifact sources, with subsequent adjustment of wavelet coefficients in respective frequency bands tailored to the distinct characteristics of each artifact. The results of synthetic and real datasets show that our proposed method maximally retains the time-domain and frequency-domain information in the EEG during denoising. Compared with existing techniques, the proposed method achieves better denoising performance, which establishes a reliable foundation for subsequent clinical analyses.
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Artefatos , Eletroencefalografia , Processamento de Sinais Assistido por Computador , Humanos , Eletroencefalografia/métodos , Algoritmos , Eletromiografia/métodos , Adulto , Análise de Ondaletas , Eletroculografia/métodos , Masculino , Adulto Jovem , FemininoRESUMO
Citrus fruits are economically significant crops worldwide, as they contain various bioactive compounds that possess health-promoting properties. Carotenoids, as the most important component in citrus, exhibit notable pharmacological activities, such as antioxidation and anticancer, which make carotenoids valuable in the prevention and treatment of breast cancer. In this study, after treatment with carotenoid extracts from XiYou (XY) and ZaoHongQiCheng (ZH), we evaluated the cytotoxicity, apoptosis, antioxidant system, and oxidative stress induced by ROS overproduction and MMP damage in MDA-MB-231 cells. The analysis confirmed that cell proliferation was inhibited in a concentration-dependent manner, accompanied by G0/G1 arrest and cell apoptosis. XY and ZH promoted the accumulation of ROS, decreased MMP, increased malondialdehyde (MDA) levels, consumed glutathione (GSH), and reduced the activity of antioxidant enzymes (peroxidase (POD), catalase (CAT), glutathione reductase (GR), and superoxide dismutase (SOD)). Meanwhile, XY and ZH induced apoptosis through the mitochondrial pathway by significantly upregulated P53, BAX, caspase-3, caspase-7, and caspase-9 gene expression levels and downregulated Bcl-2. Carotenoid-rich extracts were found to cause oxidative stress by enhancing ROS production through their pro-oxidative potential, and the aggravation of oxidative processes promotes apoptosis in MDA-MB-231 cells. These results indicate that citrus carotenoids can be used as potential pro-oxidants and have the potential to be developed into products for the prevention or treatment of breast cancer.
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A convenient, low-cost, and rapid detection of BmNPV-infected silkworms is of great significance for the safety of the sericulture industry. In this study, a portable NIR system was used to collect the spectra of normal silkworms and the infected silkworms induced by the administration of Bombyx mori nuclear polyhedrosis virus (BmNPV). Different spectral pretreatment methods were applied, then principal component analysis (PCA), linear discriminant analysis (LDA), and partial least squares discriminant analysis (PLSDA) were used for the classification analysis. The results showed that PCA and LDA were unable to achieve the purpose. For the PLSDA calibration, after the pretreatment of SNV combining 2nd derivative, it had a high identification performance, and obtained low classification errors of 0.023, 0.033, and 0.030 for the calibration set, cross-validation set, and test set, respectively, with higher sensitivity and specificity. Therefore, the BmNPV-infected silkworms can be identified by portable NIR spectroscopy, which will effectively reduce losses for the sericulture industry.
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Bombyx , Nucleopoliedrovírus , Animais , Espectroscopia de Luz Próxima ao Infravermelho/métodos , QuimiometriaRESUMO
BACKGROUND: The multidose Sabin-strain inactivated poliovirus vaccine (sIPV) has the potential to significantly aid in the eradication of poliomyelitis, particularly in low- and middle-income countries. As part of a phase III clinical trial in which infants were given three doses of primary immunization at 2, 3, and 4 months of age, this study aimed to evaluate immune persistence following primary immunization, as well as the safety and immunogenicity of a booster of the 5-dose sIPV in infants aged 18 months. METHODS: Infants aged 18 months were given one booster dose of 5-dose sIPV in stage one, which was open-label. Unblinding was performed for stage two after completing primary immunization, which was randomized, blinded, and controlled; infants aged 18 months in the test group I-III, IPV group, and single-dose sIPV group were given one booster dose of 5-dose sIPV, conventional IPV, and single-dose sIPV, respectively, in stage two. RESULTS: This study included 1438 infants in the immune persistence and safety set and 1387 infants in the booster per-protocol set. Fourteen months after primary immunization, the seropositivity rates (≥1:8) for types 1-3 were 100%, 99.88%, and 99.53% in the 5-dose sIPV groups; 100%, 98.97%, and 97.23% in the IPV group; and 99.66%, 100%, and 99.66% in the single-dose sIPV group. A total of 30 days after booster immunization, the seropositivity rates (≥1:8) of 3 serotypes in all the groups reached 100%. The geometric mean titers of neutralizing antibodies for types 1-3 in the 5-dose sIPV group were 9962.89, 10273, and 7870.21, with geometric mean increases of 15.76, 33.15, and 24.5, compared to the pre-booster level. The overall incidence of adverse reactions was 8.97%, with fever being the most common, observed at rates of 7.1%, 5.52%, and 7.96% in the 5-dose sIPV, IPV, and single-dose groups, respectively (p = 0.4845). CONCLUSIONS: The 5-dose sIPV has shown promising immune persistence and robust immune response following a booster immunization, coupled with an acceptable safety profile.
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Simultaneous improvement of strength and conductivity is urgently demanded but challenging for bimetallic materials. Here we show by creating a self-assembled lamellar (SAL) architecture in W-Cu system, enhancement in strength and electrical conductivity is able to be achieved at the same time. The SAL architecture features alternately stacked Cu layers and W lamellae containing high-density dislocations. This unique layout not only enables predominant stress partitioning in the W phase, but also promotes hetero-deformation induced strengthening. In addition, the SAL architecture possesses strong crack-buffering effect and damage tolerance. Meanwhile, it provides continuous conducting channels for electrons and reduces interface scattering. As a result, a yield strength that doubles the value of the counterpart, an increased electrical conductivity, and a large plasticity were achieved simultaneously in the SAL W-Cu composite. This study proposes a flexible strategy of architecture design and an effective method for manufacturing bimetallic composites with excellent integrated properties.
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Autophagy in eukaryotes functions to maintain homeostasis by degradation and recycling of long-lived and unwanted cellular materials. Autophagy plays important roles in pathogenicity of various fungal pathogens, suggesting that autophagy is a novel target for development of antifungal compounds. Here, we describe bioluminescence resonance energy transfer (BRET)-based high-throughput screening (HTS) strategy to identify compounds that inhibit fungal ATG4 cysteine protease-mediated cleavage of ATG8 that is critical for autophagosome formation. We identified ebselen (EB) and its analogs ebselen oxide (EO) and 2-(4-methylphenyl)-1,2-benzisothiazol-3(2H)-one (PT) as inhibitors of fungal pathogens Botrytis cinerea and Magnaporthe oryzae ATG4-mediated ATG8 processing. The EB and its analogs inhibit spore germination, hyphal development, and appressorium formation in Ascomycota pathogens, B. cinerea, M. oryzae, Sclerotinia sclerotiorum and Monilinia fructicola. Treatment with EB and its analogs significantly reduced fungal pathogenicity. Our findings provide molecular insights to develop the next generation of antifungal compounds by targeting autophagy in important fungal pathogens.