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Emotions, bodily sensations and movement are integral parts of musical experiences. Yet, it remains unknown i) whether emotional connotations and structural features of music elicit discrete bodily sensations and ii) whether these sensations are culturally consistent. We addressed these questions in a cross-cultural study with Western (European and North American, n = 903) and East Asian (Chinese, n = 1035). We precented participants with silhouettes of human bodies and asked them to indicate the bodily regions whose activity they felt changing while listening to Western and Asian musical pieces with varying emotional and acoustic qualities. The resulting bodily sensation maps (BSMs) varied as a function of the emotional qualities of the songs, particularly in the limb, chest, and head regions. Music-induced emotions and corresponding BSMs were replicable across Western and East Asian subjects. The BSMs clustered similarly across cultures, and cluster structures were similar for BSMs and self-reports of emotional experience. The acoustic and structural features of music were consistently associated with the emotion ratings and music-induced bodily sensations across cultures. These results highlight the importance of subjective bodily experience in music-induced emotions and demonstrate consistent associations between musical features, music-induced emotions, and bodily sensations across distant cultures.
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Música , Humanos , Música/psicologia , Sensação , Comparação Transcultural , Acústica , Emoções , Percepção AuditivaRESUMO
BACKGROUND: Neuroblastoma (NB) is the most prevalent and deadliest pediatric solid tumor. With of over 50% of high-risk neuroblastoma cases relapse, the imperative for novel drug targets and therapeutic strategies is accentuated. In neuroblastoma, the existence of tumor-associated macrophages (TAMs) correlates with an unfavorable patient prognosis. However, the clinical relevance and prognostic implications of regulatory genes linked to TAMs infiltration in neuroblastoma remain unclear, and further study is required. METHODS: We conducted a comprehensive analysis utilizing transcriptome expression profiles from three primary datasets associated with neuroblastoma (GSE45547, GSE49710, TARGET) to identify hub genes implicated in immune evasion within neuroblastoma. Subsequently, we utilized single-cell RNA sequencing analysis on 17 clinical neuroblastoma samples to investigate the expression and distribution of these hub genes, leading to the identification of TNFAIP3. The above three public databases were merged to allowed for the validation of TNFAIP3's molecular functions through GO and KEGG analysis. Furthermore, we assessed TNFAIP3's correlation with immune infiltration and its potential immunotherapeutic impact by multiple algorithms. Our single-cell transcriptome data revealed the role of TNFAIP3 in macrophage polarization. Finally, preliminary experimental verifications to confirm the biological functions of TNFAIP3-mediated TAMs in NB. RESULTS: A total of 6 genes related to immune evasion were screened and we found that TNFAIP3 exhibited notably higher expression in macrophages than other immune cell types, based on the scRNA-sequencing data. GO and KEGG analysis showed that low expression of TNFAIP3 significantly correlated with the activation of multiple oncogenic pathways as well as immune-related pathways. Then validation affirmed that individuals within the TNFAIP3 high-expression cohort could potentially derive greater advantages from immunotherapeutic interventions, alongside exhibiting heightened immune responsiveness. Deciphering the pseudotime trajectory of macrophages, we revealed the potential of TNFAIP3 in inducing the polarization of macrophages towards the M1 phenotype. Finally, we confirmed that patients in the TNFAIP3 high expression group might benefit more from immunotherapy or chemotherapy as substantiated by RT-qPCR and immunofluorescence examinations. Moreover, the role of TNFAIP3 in macrophage polarization was validated. Preliminary experiment showed that TNFAIP3-mediated TAMs inhibit the proliferation, migration and invasion capabilities of NB cells. CONCLUSIONS: Our results suggest that TNFAIP3 was first identified as a promising biomarker for immunotherapy and potential molecular target in NB. Besides, the presence of TNFAIP3 within TAMs may offer a novel therapeutic strategy for NB.
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Biomarcadores Tumorais , Neuroblastoma , Proteína 3 Induzida por Fator de Necrose Tumoral alfa , Humanos , Neuroblastoma/genética , Neuroblastoma/imunologia , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Biomarcadores Tumorais/genética , Prognóstico , Perfilação da Expressão Gênica , Transcriptoma , Macrófagos Associados a Tumor/imunologia , Evasão Tumoral/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Calcium is the main mineral responsible for healthy bone growth in infants. Laser-induced breakdown spectroscopy (LIBS) was combined with a variable importance-based long short-term memory (VI-LSTM) for the quantitative analysis of calcium in infant formula powder. First, the full spectra were used to establish PLS (partial least squares) and LSTM models. The R2 and root-mean-square error (RMSE) of the test set (R P2 and R M S E P) were 0.1460 and 0.0093 in the PLS method, respectively, and 0.1454 and 0.0091 in the LSTM model, respectively. To improve the quantitative performance, variable selection based on variable importance was introduced to evaluate the contribution of input variables. The variable importance-based PLS (VI-PLS) model had R P2 and R M S E P of 0.1454 and 0.0091, respectively, whereas the VI-LSTM model had R P2 and R M S E P of 0.9845 and 0.0037, respectively. Compared with the LSTM model, the number of input variables in the VI-LSTM model was reduced to 276, R P2 was improved by 114.63%, and R M S E P was reduced by 46.38%. The mean relative error of the VI-LSTM model was 3.33%. We confirm the predictive ability of the VI-LSTM model for the calcium element in infant formula powder. Thus, combining VI-LSTM modeling and LIBS has great potential for the quantitative elemental analysis of dairy products.
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Cálcio , Fórmulas Infantis , Lactente , Humanos , Cálcio/análise , Pós , Memória de Curto Prazo , Análise Espectral/métodos , LasersRESUMO
Background: Total hip arthroplasty (THA) has emerged as a pivotal approach for addressing femoral neck fractures (FNFs), a prevalent type of fracture in older people. Restoring joint functionality following surgery significantly contributes to patients' overall well-being. Therefore, the implementation of rational and effective rehabilitation exercises is crucial. Objective: This study aims to investigate the impact of phased rehabilitation management on patients with FNFs who have undergone THA. Methods: In this prospective comparative study, a total of 89 patients were enrolled. Among them, 49 patients underwent phased rehabilitation management, while 40 patients received conventional postoperative rehabilitation. The evaluation encompassed a range of assessments, including the Harris Hip Score (HHS) for the evaluation of hip joint function, the Five-Times-Sit-to-Stand Test (FTSST) to quantify lower limb muscle strength, the Barthel Index to assess activities of daily living, and the Visual Analog Scale (VAS) to measure pain intensity. Furthermore, preoperative and postoperative serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were diligently measured to provide a comprehensive understanding of the patient's inflammatory responses. Results: Overall, the study group exhibited a significantly higher average HHS after surgery compared to the control group. Notably, the VAS scores at 1 day and 3 days post-surgery in both groups demonstrated a reduced trend compared to preoperative values. This trend was more significant in the study group compared to the control group. The time taken for the FTSST in patients undergoing phased rehabilitation management was less compared to the control group. Furthermore, phased rehabilitation management was associated with more significant improvements in activities of daily living. Notably, IL-6 levels were higher in both the study and control groups at 1 day postoperatively than before surgery, while they decreased at 3 days postoperatively compared to the 1-day mark. The study group exhibited significantly lower levels of CRP (mg/L) and ESR (mm/h) compared to the control group. Conclusions: Implementing phased rehabilitation management for patients with FNFs following THA improves hip joint function, lower limb muscle strength, daily living activities, pain intensity, and inflammatory response.
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Artroplastia de Quadril , Fraturas do Colo Femoral , Humanos , Idoso , Artroplastia de Quadril/reabilitação , Atividades Cotidianas , Estudos Prospectivos , Interleucina-6 , Resultado do Tratamento , Fraturas do Colo Femoral/cirurgiaRESUMO
A hydroxamic acid based microtubule-destabilizing agent (MDA) SKLB-14b was discovered in this study, which was derived from shortening the linker length of the HDAC6 and microtubule dual-target inhibitor SKLB-23bb. SKLB-14b exhibited low nanomolar IC50 values on a wide spectrum of human cancer cell lines including both sensitive and multidrug-resistant cell lines. Surprisingly, its anti-proliferative activity relied on the presence of the hydroxamic acid group but lost inhibitory activity against HDACs. SKLB-14b bound to the colchicine site of tubulin and could inhibit tubulin polymerization. It exhibited good metabolic stability in liver microsomes, no inhibitory effect on CYP450 isoenzymes and high oral bioavailability. In vivo experiments revealed that SKLB-14b was potent in both sensitive (A2780S, HCT116) and resistant (A2780/T) xenograft mice models. Furthermore, in the patient-derived tumor xenograft (PDX) models of osimertinib resistant non-small cell lung cancer (NSCLC), 50 mg/kg of SKLB-14b administered every twodays inhibited tumor growth by 70.6% without obvious toxicity, better than the 59.7% inhibition rate of paclitaxel. Mechanistically, we found that SKLB-14b exerted anti-tumor and anti-multidrug resistance effects in vitro and in vivo through cell cycle arrest and pro-apoptotic activities, as well as vascular disrupting activities. Therefore, we discovered that SKLB-14b, as a novel MDA based on hydroxamic acid, could serve as a potential drug candidate for cancer therapy which deserves further investigation.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias Ovarianas , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Ácidos Hidroxâmicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Microtúbulos , Neoplasias Ovarianas/tratamento farmacológico , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Phenyllactic acid (PLA) has been demonstrated to possess antibacterial activity and capacity to prolong food shelf life. However, studies on the performance of PLA in inhibiting Staphylococcus aureus and its effectiveness when applied to dairy products are largely lacking. Here, antibacterial activity (planktonic and biofilm states) of PLA against S. aureus CICC10145 (S. aureus_45) were investigated. The results showed that PLA inhibited growth of S. aureus_45 and formation of S. aureus_45 biofilm. Next, the antibacterial action target of PLA was uncovered from both physiological and phenotypic perspectives. The results showed that PLA decreased cell metabolic activity and cell viability, damaged cell membrane integrity, triggered leakage of intracellular contents (DNA, proteins, and ATP), and caused oxidative stress damage and morphological deformation of S. aureus_45. In practical application, the antibacterial activity of PLA against S. aureus_45 cells was further confirmed in skim milk and cheese as dairy food models, and the antibacterial effects can be adequately maintained during storage for 21 d, at least at 4°C. These findings suggested that PLA could be a potential candidate for controlling S. aureus outgrowth in dairy foods.
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Queijo , Infecções Estafilocócicas , Animais , Staphylococcus aureus , Queijo/microbiologia , Leite/microbiologia , Infecções Estafilocócicas/veterinária , Antibacterianos/farmacologia , PoliésteresRESUMO
Staphylococcus aureus and its biofilm have emerged as a significant threat to the safety of dairy products. In recent years, lactic acid bacteria (LAB) bacteriocins have been widely acknowledged as the potential natural antibacterial substance in food biopreservation due to their excellent antibacterial effects. However, few LAB bacteriocins with antibacterial and antibiofilm activity against S. aureus have been reported in dairy products. In the present study, a novel bacteriocin LSX01 of Lactobacillus paracasei LS-6 isolated from a traditional fermented yogurt produced in Yunnan, China, was purified and characterized extensively. The LSX01 possessed a molecular weight of 967.49 Da and an AA sequence of LDQAGISYT. The minimum inhibitory concentration of LSX01 against S. aureus_45 was 16.90 µg/mL, which was close to or lower than the previously reported bacteriocins. The LSX01 exhibited an extensive antimicrobial spectrum against both gram-positive and gram-negative bacteria. Moreover, LSX01 exhibited excellent tolerance to heat and acid-base treatments, and sensitivity to the proteolytic enzymes, such as pepsin and proteinase K. Furthermore, the treatment of S. aureus_45 planktonic cells with LSX01 significantly reduced their metabolic activity and disrupted the cell membrane integrity. Scan electron microscopy results demonstrated that LSX01 induced cytoplasmic content leakage and cell deformation. Additionally, biofilm formation of S. aureus_45 was also significantly inhibited by LSX01. Overall, the results suggested that the novel LAB bacteriocin LSX01 possessed antibacterial activity and antibiofilm activity against S. aureus and, hence, could have potential for improving safety of dairy products.
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Bacteriocinas , Lacticaseibacillus paracasei , Animais , Antibacterianos/metabolismo , Bacteriocinas/farmacologia , Biofilmes , China , Bactérias Gram-Negativas , Lactobacillus/metabolismo , Lacticaseibacillus paracasei/metabolismo , Staphylococcus aureus , IogurteRESUMO
Histone deacetylases (HDACs) play a key role in the homeostasis of protein acetylation in histones and have recently emerged as a therapeutic target for numerous diseases. The inhibition of HDACs may block angiogenesis, arrest cell growth, and lead to differentiation and apoptosis in tumour cells. Thus, HDAC inhibitors (HDACi) have received increasing attention and many of which are developed from natural sources. In the past few decades, naturally occurring HDACi have been identified to have potent anticancer activities, some of which have demonstrated promising therapeutic effects on haematological malignancies. In this review, we summarized the discovery and modification of HDAC inhibitors from natural sources, novel drug design that uses natural products as parent nuclei, and dual target design strategies that combine HDAC with non-HDAC targets.
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Produtos Biológicos/farmacologia , Desenho de Fármacos , Descoberta de Drogas , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Produtos Biológicos/síntese química , Produtos Biológicos/química , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Estrutura MolecularRESUMO
A new ion-exchange medium was prepared from magnetic particles of â¼1.0 µm through coating with small zwitterions and then functionalizing with ampholytic groups for the isoelectric point of â¼6.4 and denoted MSP-ZEWB. With Meyerozyma guilliermondii uricase (MGU) as the model of soluble proteins, the purification of a protein via ion-exchange was compared between MSP-ZEWB through elution in discontinuous mode and Toyopearl SP-650C as a classical ion-exchange medium through elution in continuous mode. MGU was adsorbed at pH 7.6 or 8.0 and eluted via competitive displacement by NaCl or electrostatic repulsions with an elution buffer at pH 10 to reverse the type of net charges of MGU. From MSP-ZEWB, MGU was eluted more rapidly with the elution percentages higher than those from Toyopearl SP-650C. For yielding a unit of MGU activity, MSP-ZEWB gave the elution solution volumes that were â¼50% of those obtained with Toyopearl SP-650C. The yields of MGU of the highest purity from MSP-ZEWB were higher than those from Toyopearl SP-650C, but the highest purification folds with both media were comparable. MSP-ZEWB regenerated for 16 times still showed the consistent purification efficacy. Therefore, the ion-exchange media bearing small zwitterion coats showed great promise for the purification of soluble proteins.
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Meios de Cultura/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/isolamento & purificação , Saccharomycetales/enzimologia , Urato Oxidase/química , Urato Oxidase/isolamento & purificação , Adsorção , Cromatografia por Troca Iônica/métodos , Proteínas Fúngicas/metabolismo , Concentração de Íons de Hidrogênio , Cloreto de Sódio/metabolismo , Solubilidade , Eletricidade Estática , Urato Oxidase/metabolismoRESUMO
Whole milk powder and skimmed milk powder are suitable for different groups of people due to their differences in composition. Therefore, a rapid classification method for whole milk powder and skimmed milk powder is urgently needed. In this paper, a novel strategy based on laser-induced breakdown spectroscopy (LIBS) and feature processing methods combined with logistic regression (LR) was constructed for the classification of milk powder. A LR classification model based on mini-batch gradient descent (MGD) was employed first. As indicated by the research results, the accuracy of the MGD-LR model for the milk powder samples in the test set is 96.33% and the modeling time is 33.07 s. The modeling efficiency is low and needs to be improved. Principal components analysis (PCA) and mutual information (MI) were used as feature processing methods to reduce the high dimensional LIBS data into fewer features for improving the modeling efficiency of the classification model. The research results indicate that the accuracy of the PCA-MGD-LR model and the MI-MGD-LR model for the test set of milk powder samples was 99.33% and 99.67%, respectively. Compared with MGD-LR model, the modeling efficiency of PCA-MGD-LR and MI-MGD-LR models has increased by 89.7% and 74.8%, respectively. The results fully demonstrate the feasibility of rapid milk powder classification based on LIBS and feature processing methods combined with LR, and it will provide a new technology for the identification and classification of milk powder.
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Lasers , Leite , Humanos , Animais , Leite/química , Pós/análise , Modelos Logísticos , Análise Espectral/métodosRESUMO
Due to the increasing demand for higher security and low-cost energy storage systems, the main research focus has been developing a suitable substitute for lithium-ion batteries. Aqueous zinc ion batteries (AZIBs) are considered the best alternative to lithium-ion batteries in large-scale energy storage devices. Owing to its high capacity, vanadate is a promising cathode material for AZIBs. The crystallographic orientation of cathode materials dramatically influences the rate performance and cycling life. Here, Mg0.57V5O12·2.3H2O (MgVO) with favorable (001) crystal orientation and significantly improved electrochemical performance is prepared by a simple stirring method. The crystal growth orientations of MgVO are altered by adjusting the aging time of the reactant solution. The (001)-orientated grain growth of MgVO delivers a 232.5 mA h g-1 capacity at 5 A g-1 with a 94% capacity retention rate after 1400 cycles. The zinc ion storage performance of MgVO demonstrates that the orientation-controlled method can design effective cathode materials for high-performance ZIBs.
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Boletus aereus Fr. ex Bull. stands out as a delectable edible mushroom with high nutritional and medicinal values, featuring polysaccharides as its primary nutrient composition. In our continuous exploration of its beneficial substances, a novel polysaccharide (BAPN-1) with a molecular weight of 2279 kDa was prepared. It was identified as a glucan with a backbone composed of the residues â4)-α-Glcp-(1â and â4,6)-α-Glcp-(1â connected in a proportion of 5:1 and a ß-Glcp-(1â side residue attached at C6 of the â4,6)-α-Glcp-(1â residue. Biologically, BAPN-1 exhibited broad-spectrum antiproliferative activities against various NHL cells, including HuT-78, OCI-LY1, OCI-LY18, Jurkat, RL, and Karpas-299, with IC50 values of 0.73, 1.21, 3.18, 1.52, 3.34, and 4.25 mg/mL, respectively. Additionally, BAPN-1 significantly induced cell cycle arrest in the G2/M phase and caused apoptosis of NHL cells. Mechanistically, bulk RNA sequencing and Western blot analysis revealed that BAPN-1 could upregulate cyclin B1 and enhance cleaved caspase-9 expression through the inhibition of FGFR3 and RAF-MEK-ERK signaling pathways. This work supports the improved utilization of B. aereus in high-value health products.
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Antineoplásicos , Apoptose , Proliferação de Células , Linfoma não Hodgkin , Polissacarídeos , Humanos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Linfoma não Hodgkin/tratamento farmacológico , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Peso Molecular , Basidiomycota/químicaRESUMO
Milk powder can provide the necessary nutrients for the growth of infants, and the level of its energy value is an important factor in the measurement of its nutritional value. Therefore, the measurement of the energy value in milk powder is of great significance for the nutritional health of infants. In this study, samples of 32 different brands of milk powder were selected for spectral analysis, and laser-induced breakdown spectroscopy (LIBS) combined with deep belief network (DBN), back propagation (BP) neural network, and long short-term memory (LSTM) models was used to achieve quantitative analysis of the energy value of the milk powder. The experimental results revealed that the LSTM model outperformed the DBN and BP models in terms of accuracy, with a mean relative error (MREP) of 1.0029%, which was 73.03% lower than that of DBN (3.7186%) and 69.53% lower than that of BP (3.2914%). Moreover, the determination coefficient (RP2) value improved significantly from 0.9341 for DBN and 0.9766 for BP to 0.9984. In addition, the root mean square error (RMSEP) decreased to 0.2140 from 0.7042 for DBN and 0.9051 for BP. These results demonstrate that the LSTM model has superior predictive performance compared to the other models. Therefore, the combination of LIBS and LSTM can accurately measure the energy value of milk powder and provide an effective and feasible means for its commercial measurement.
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Memória de Curto Prazo , Leite , Lactente , Humanos , Animais , Pós , Memória de Longo Prazo , LasersRESUMO
The mechanisms underlying the toxicity of environmental stress are unclear for marine macrobenthos. Copper/Cu has posed the most serious threats to amphioxus, an ancient and model benthic cephalochordate. Herein, a dynamic change in the physiological parameters (GR, SOD, ATP, and MDA) was detected with ROS accumulation in Branchiostoma belcheri exposed to 0.3 mg·L-1 Cu. Transcriptomes and microRNAomes of B. belcheri were generated to investigate the molecular mechanisms by which this amphioxus copes with Cu exposure. Time-specific genes identified at different time points after exposure were involved in the stimulus and immune response, detoxification and ionic homeostasis, aging and the nervous system, sequentially, with prolongation of exposure time, forming a dynamic process of molecular response to Cu stress. In total, 57 differentially expressed miRNAs were identified under Cu stress. Transcriptomics-miRNAomics analyses indicate that these miRNAs targeted genes associated with many key biological processes such as xenobiotics degradation, oxidative stress, and energy metabolism. The constructed miRNA-mRNA-pathway network uncovered a broad post-transcriptional regulatory mechanism in B. belcheri to cope with Cu stress. Overall, this integrated analyses show that enhanced defense response, accelerated ROS elimination, and repressed ATP production constitute a comprehensive strategy to cope with Cu toxicity in the ancient macrobenthos.
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Anfioxos , MicroRNAs , Animais , Transcriptoma , Cobre/toxicidade , Cobre/metabolismo , Espécies Reativas de Oxigênio/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Trifosfato de Adenosina/metabolismoRESUMO
Knowledge about the impact of different dissolved oxygen (DO) on the composition and function of gut bacteria of aquatic insects is largely unknown. Herein, we constructed freshwater environments with different DOs (hypoxia: 2.50 ± 0.50, normoxia: 7.00 ± 0.50, and hyperoxia: 13.00 ± 0.50 mg/L) where aquatic firefly Aquatica leii larvae lived for three months. Their gut flora was analyzed using the combination of 16S rRNA amplicon sequencing and metagenomics. The results showed no difference in alpha diversity of the gut flora between A. leii inhabiting various DOs. However, the relative abundance of several bacterial lineages presented significant changes, such as Pseudomonas. In addition, bacterial genes with an altered relative abundance in response to various DOs were primarily related to metabolism. The alteration of these functions correlated with the DO change. This is the first to uncover structure of gut flora under various DOs in aquatic insect larvae.
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Photodeposition of dual-cocatalysts Pt-Cr or Rh-Cr on the surface of ZnIn2S4 is used to achieve overall water splitting. Compared with the hybrid loading of the Pt element and Cr element, the formation of the Rh-S bond results in space separation of the Rh element and Cr element. The Rh-S bond and space separation of cocatalysts promote the transfer of bulk carriers to the surface and inhibit self-corrosion.
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Chemical fertilizers are important for effectively improving soil fertility, promoting crop growth, and increasing grain yield. Therefore, methods that can quickly and accurately measure the amount of fertilizer in the soil should be developed. In this study, 20 groups of soil samples were analyzed using laser-induced breakdown spectroscopy, and partial least squares (PLS) and random forest (RF) models were established. The prediction performances of the models for the chemical fertilizer content and pH were analyzed as well. The experimental results showed that the R 2 and root mean square error (RMSE) of the chemical fertilizer content in the soil obtained using the full-spectrum PLS model were .7852 and 2.2700 respectively. The predicted R 2 for soil pH was .7290, and RMSE was .2364. At the same time, the full-spectrum RF model showed R 2 of .9471 (an increase of 21%) and RMSE of .3021 (a decrease of 87%) for fertilizer content. R 2 for the soil pH under the RF model was .9517 (an increase of 31%), whereas RMSE was .0298 (a decrease of 87%). Therefore, the RF model showed better prediction performance than the PLS model. The results of this study show that the combination of laser-induced breakdown spectroscopy with RF algorithm is a feasible method for rapid determination of soil fertilizer content.
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Purinostat Mesylate (PM) is a novel highly selective and active HDAC I/IIb inhibitor, and the injectable formulation of PM (PMF) based on the compound prescription containing cyclodextrin completely can overcome PM's poor solubility and improves its stability and pharmacokinetic properties. Here, we showed that PM effectively repressed the survival of Ph+ leukemia cells and CD34+ leukemia cells from CML patients in vitro. In vivo studies demonstrated that PMF significantly prevented BCR-ABL(T315I) induced CML progression by restraining leukemia stem cells (LSCs), which are insensitive to chemotherapy and responsible for CML relapse. Mechanism studies revealed that targeting HDAC I/IIb repressed several important factors for LSCs survival including c-Myc, ß-Catenin, E2f, Ezh2, Alox5, and mTOR, as well as interrupted some critical biologic processes. Additionally, PMF increased glutamate metabolism in LSCs by increasing GLS1. The combination of PMF and glutaminase inhibitor BPTES synergistically eradicated LSCs by altering multiple key proteins and signaling pathways which are critical for LSC survival and self-renewal. Overall, our findings represent a new therapeutic strategy for eliminating LSCs by targeting HDAC I/IIb and glutaminolysis, which potentially provides a guidance for PMF clinical trials in the future for TKI resistance CML patients.
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We report herein that TSPAN32 is a key node factor for Philadelphia (Ph+) leukemia pathogenesis. We found that TSPAN32 expression was repressed by BCR-ABL and ectopic TSPAN32 expression upon Imatinib treatment inhibited the proliferation of Ph+ cell lines. Tspan32 overexpression significantly prevented BCR-ABL induced leukemia progression in a murine model and impaired leukemia stem cell (LSC) proliferation. LSCs represent an obstacle for chronic myeloid leukemia (CML) elimination, which continually replenish leukemia cells and are associated with disease relapse. Therefore, the identification of essential targets that contribute to the survival and self-renewal of LSCs is important for novel curative CML. Mechanistically, TSPAN32 was shown to interact with PTEN, increased its protein level and caused a reduction in PI3K-AKT signaling activity. We also found that TSPAN32 was repressed by BCR-ABL via the suppression of an important transcription factor, TAL1. Ectopic expression of TAL1 significantly increased TSPAN32 mRNA and protein level, which indicated that BCR-ABL repressed TSPAN32 transcription by decreasing TAL1 expression. Overall, we identified a new signaling axis composed of "BCR-ABL-TAL1-TSPAN32-PTEN-PI3K-AKT". Our findings further complement the known mechanisms underlying the transformation potential of BCR-ABL in CML pathogenesis. This new signaling axis also provides a potential means to target PI3K-AKT for CML treatment.
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Leucemia Mielogênica Crônica BCR-ABL Positiva , PTEN Fosfo-Hidrolase , Tetraspaninas , Animais , Camundongos , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Tetraspaninas/metabolismoRESUMO
Stable rheological properties of ceramic ink are a key requirement for inkjet printing (IJP), which should be satisfied in terms of the Reynolds and Weber numbers. In this paper, the reverse microemulsion was introduced for the synthesis of monodispersed nanosized ceramic powders, and the average size was less than 100 nm. A comparison of two different dispersants, i.e., polyacrylic ammonium (PAANH4) and polyacrylic aid (PAA), revealed that the former exerted a good dispersion effect on the ceramic ink. The sedimentation ratio, zeta potential, surface tension, viscosity, and density of the inks were measured, and the Reynolds and Weber numbers, as well as Z value, were calculated. A stable, homogeneous, and high solid loading (20 wt%) ceramic ink could be achieved after aging for a period of 72 h. Finally, the ceramic inks showed the desired printable property in the inkjet printing process. Combining inkjet printing technology with a sintering process, Ni-Mn-O films have the potential to monitor temperature and humidity parameters for intelligent wearable devices.