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BACKGROUND: Deciphering the molecular dynamics (MD) of rotaxanes is crucial for designing and refining their applications in molecular devices. This study employed fluorine-19 nuclear magnetic resonance (19F NMR) and magnetic resonance imaging (MRI) to unveil the interplay between mechanical bonds and steric hindrance in a series of fluorinated rotaxanes. RESULTS: 1H/19F NMR revealed stable "Z"-shaped wheel conformations minimizing steric clashes and favoring π-π interactions with the axle. Utilizing fluorines and axle protons as reporters, 1H/19F relaxation rates and solid-state 19F NMR studies demonstrated that mechanical bond primarily governs wheel motion, while steric hindrance dictates axle movement. Intriguingly, mechanical bond mainly affects local axle groups, leaving distant ones minimally impacted. MD simulations corroborated these findings. Temperature-dependent 19F NMR indicated that energy input enhances rotational motion and wheel conformational transitions. Furthermore, the drastic increase in 19F relaxation rates upon mechanical bond formation and steric hindrance enables sensitive and selective 19F MRI visualization of MD changes. SIGNIFICANCE: This study, by elucidating the roles of internal and external factors on rotaxane molecular dynamics using 19F NMR/MRI, offers valuable insights that can advance the field of rotaxane-based molecular devices.
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Background: For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. Methods: We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Results: Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. Conclusions: The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.
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Polyarthrite rhumatoïde , Analyse de profil d'expression de gènes , Transcriptome , Polyarthrite rhumatoïde/génétique , Polyarthrite rhumatoïde/immunologie , Polyarthrite rhumatoïde/traitement médicamenteux , Polyarthrite rhumatoïde/diagnostic , Humains , Antirhumatismaux/usage thérapeutique , Agranulocytes/immunologie , Agranulocytes/métabolisme , Marqueurs biologiques , Lymphocytes T CD8+/immunologieRÉSUMÉ
Electric eel is an excellent example to harness ion-concentration gradients for sustainable power generation. However, current strategies to create electric-eel-inspired power sources commonly involve manual stacking of multiple salinity-gradient power source units, resulting in low efficiency, unstable contact, and poor flexibility. Here we propose a consecutive multimaterial printing strategy to efficiently fabricate biomimetic ionic hydrogel power sources with a maximum stretchability of 137%. The consecutively-printed ionic hydrogel power source filaments showed seamless bonding interface and can maintain stable voltage outputs for 1000 stretching cycles at 100% strain. With arrayed multi-channel printhead, power sources with a maximum voltage of 208 V can be automatically printed and assembled in parallel within 30 min. The as-printed flexible power source filaments can be woven into a wristband to power a digital wristwatch. The presented strategy provides a tool to efficiently produce electric-eel-inspired ionic hydrogel power sources with great stretchability for various flexible power source applications.
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Background: Creatinine-cystatin C ratio (CCR) has been demonstrated as an objective marker of sarcopenia in clinical conditions but has not been evaluated as an osteoporosis marker in individuals with normal renal function. Methods: We selected 271,831 participants with normal renal function from UK Biobank cohort. Multivariable linear/logistic regression and Cox proportional hazards model were used to investigate the phenotypic relationship between CCR and osteoporosis in total subjects and gender-stratified subjects. Based on the genome-wide association study (GWAS) data, linkage disequilibrium regression (LDSC) and Mendelian randomization (MR) analysis were performed to reveal the shared genetic correlations and infer the causal effects, respectively. Results: Amongst total subjects and gender-stratified subjects, serum CCR was positively associated with eBMD after adjusting for potential risk factors (all P<0.05). The multivariable logistic regression model showed that the decrease in CCR was associated with a higher risk of osteoporosis/fracture in all models (all P<0.05). In the multivariable Cox regression analysis with adjustment for potential confounders, reduced CCR is associated with the incidence of osteoporosis and fracture in both total subjects and gender-stratified subjects (all P<0.05). A significant non-linear dose-response was observed between CCR and osteoporosis/fracture risk (P non-linearity < 0.05). LDSC found no significant shared genetic effects by them, but PLACO identified 42 pleiotropic SNPs shared by CCR and fracture (P<5×10-8). MR analyses indicated the causal effect from CCR to osteoporosis/fracture. Conclusions: Reduced CCR predicted increased risks of osteoporosis/fracture, and significant causal effects support their associations. These findings indicated that the muscle-origin serum CCR was a potential biomarker to assess the risks of osteoporosis and fracture.
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Marqueurs biologiques , Créatinine , Cystatine C , Analyse de randomisation mendélienne , Ostéoporose , Humains , Femelle , Mâle , Ostéoporose/génétique , Ostéoporose/sang , Ostéoporose/épidémiologie , Adulte d'âge moyen , Marqueurs biologiques/sang , Créatinine/sang , Cystatine C/sang , Cystatine C/génétique , Sujet âgé , Étude d'association pangénomique , Polymorphisme de nucléotide simple , Adulte , Densité osseuse/génétique , Facteurs de risqueRÉSUMÉ
BACKGROUND: Multiple metals exposure has been revealed to be related to metabolic syndrome (MetS). However, the associations and interactions between multiple metals exposure and MetS are remains controversial, and the potential mechanism of the above-mentioned is still unclear. METHODS: The associations between urinary metals and the MetS were analyzed by multivariable logistic regression model and restricted cubic spline (RCS). Bayesian kernel machine regression (BKMR) model and quantile-based g-computation (qgcomp) were applied to explore the mixed exposure and interaction effect of metals. Mediation analysis was used to explore the role of liver function. RESULTS: In the single metal model, multiple metals were significantly associated with MetS. RCS analysis further verified the associations between 8 metals and MetS. BKMR model and qgcomp showed that zinc (Zn), iron (Fe), and tellurium (Te) were the main factors affecting the overall effect. In addition, mediation analysis indicated that serum alanine aminotransferase (ALT) mediated 21.54% and 13.29% in the associations of vanadium (V) and Zn with the risk of MetS, respectively. CONCLUSIONS: Elevated urinary concentration of Zn, V, Te, copper (Cu), molybdenum (Mo), and thallium (Tl) were related to the increased risk of MetS. Conversely, Fe and selenium (Se) may be protective factors for MetS in mixed exposure. Liver function may play a key role in the association of V and Zn exposure with MetS.
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Foie , Syndrome métabolique X , Métaux , Humains , Syndrome métabolique X/urine , Mâle , Femelle , Sujet âgé , Foie/métabolisme , Métaux/urine , Vie autonome , Adulte d'âge moyen , Chine , Peuples d'Asie de l'EstRÉSUMÉ
Lysine-specific peptide and protein modification strategies are widely used to study charge-related functions and applications. However, these strategies often result in the loss of the positive charge on lysine, significantly impacting the charge-related properties of proteins. Herein, we report a strategy to preserve the positive charge and selectively convert amines in lysine side chains to amidines using nitriles and hydroxylamine under aqueous conditions. Various unprotected peptides and proteins were successfully modified with a high conversion rate. Moreover, the reactive amidine moiety and derived modification site enable subsequent secondary modifications. Notably, positive charges were retained during the modification. Therefore, positive charge-related protein properties, such as liquid-liquid phase separation behaviour of α-synuclein, were not affected. This strategy was subsequently applied to a lysine rich protein to develop an amidine-containing coacervate DNA complex with outstanding mechanical properties. Overall, our innovative strategy provides a new avenue to explore the characteristics of positively charged proteins.
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Hydroxylamine , Lysine , Lysine/composition chimique , Hydroxylamine/composition chimique , Protéines/composition chimique , Amidines/composition chimique , alpha-Synucléine/composition chimique , Peptides/composition chimiqueRÉSUMÉ
BACKGROUND: Multimorbidity has become an important health challenge in the aging population. Accumulated evidence has shown that multimorbidity has complex association patterns, but the further mechanisms underlying the association patterns are largely unknown. METHODS: Summary statistics of 14 conditions/diseases were available from the genome-wide association study (GWAS). Linkage disequilibrium score regression analysis (LDSC) was applied to estimate the genetic correlations. Pleiotropic SNPs between two genetically correlated traits were detected using pleiotropic analysis under the composite null hypothesis (PLACO). PLACO-identified SNPs were mapped to genes by Functional Mapping and Annotation of Genome-Wide Association Studies (FUMA), and gene set enrichment analysis and tissue differential expression were performed for the pleiotropic genes. Two-sample Mendelian randomization analyses assessed the bidirectional causality between conditions/diseases. RESULTS: LDSC analyses revealed the genetic correlations for 20 pairs based on different two-disease combinations of 14 conditions/diseases, and genetic correlations for 10 pairs were significant after Bonferroni adjustment (P<0.05/91 = 5.49E-04). Significant pleiotropic SNPs were detected for 11 pairs of correlated conditions/diseases. The corresponding pleiotropic genes were differentially expressed in the brain, nerves, heart, and blood vessels and enriched in gluconeogenesis and drug metabolism, biotransformation, and neurons. Comprehensive causal analyses showed strong causality between hypertension, stroke, and high cholesterol, which drive the development of multiple diseases. CONCLUSIONS: This study highlighted the complex mechanisms underlying the association patterns that include the shared genetic components and causal effects among the 14 conditions/diseases. These findings have important implications for guiding the early diagnosis, management, and treatment of comorbidities.
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Étude d'association pangénomique , Déséquilibre de liaison , Analyse de randomisation mendélienne , Multimorbidité , Polymorphisme de nucléotide simple , Humains , Prédisposition génétique à une maladie , PléiotropieRÉSUMÉ
The progress of brain cognition and learning mechanisms has provided new inspiration for the next generation of artificial intelligence (AI) and provided the biological basis for the establishment of new models and methods. Brain science can effectively improve the intelligence of existing models and systems. Compared with other reviews, this article provides a comprehensive review of brain-inspired deep learning algorithms for learning, perception, and cognition from microscopic, mesoscopic, macroscopic, and super-macroscopic perspectives. First, this article introduces the brain cognition mechanism. Then, it summarizes the existing studies on brain-inspired learning and modeling from the perspectives of neural structure, cognitive module, learning mechanism, and behavioral characteristics. Next, this article introduces the potential learning directions of brain-inspired learning from four aspects: perception, cognition, understanding, and decision-making. Finally, the top-ten open problems that brain-inspired learning, perception, and cognition currently face are summarized, and the next generation of AI technology has been prospected. This work intends to provide a quick overview of the research on brain-inspired AI algorithms and to motivate future research by illuminating the latest developments in brain science.
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Spillovers of viruses from animals to humans occur more frequently under warmer conditions, particularly arboviruses. The invasive tick species Haemaphysalis longicornis, the Asian longhorned tick, poses a significant public health threat due to its global expansion and its potential to carry a wide range of pathogens. We analyzed meta-transcriptomic data from 3595 adult H. longicornis ticks collected between 2016 and 2019 in 22 provinces across China encompassing diverse ecological conditions. Generalized additive modeling revealed that climate factors exerted a stronger influence on the virome of H. longicornis than other ecological factors, such as ecotypes, distance to coastline, animal host, tick gender, and antiviral immunity. To understand how climate changes drive the tick virome, we performed a mechanistic investigation using causality inference with emphasis on the significance of this process for public health. Our findings demonstrated that higher temperatures and lower relative humidity/precipitation contribute to variations in animal host diversity, leading to increased diversity of the tick virome, particularly the evenness of vertebrate-associated viruses. These findings may explain the evolution of tick-borne viruses into generalists across multiple hosts, thereby increasing the probability of spillover events involving tick-borne pathogens. Deep learning projections have indicated that the diversity of the H. longicornis virome is expected to increase in 81.9% of regions under the SSP8.5 scenario from 2019 to 2030. Extension of surveillance should be implemented to avert the spread of tick-borne diseases.
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Espèce introduite , Virome , Animaux , Chine , Ixodidae/virologie , Femelle , Changement climatique , Mâle , ClimatRÉSUMÉ
The spread of the influenza virus has caused devastating pandemics and huge economic losses worldwide. Antiviral drugs with diverse action modes are urgently required to overcome the challenges of viral mutation and drug resistance, and targeted protein degradation strategies constitute excellent candidates for this purpose. Herein, the first degradation of the influenza virus polymerase acidic (PA) protein using small-molecule degraders developed by hydrophobic tagging (HyT) technology to effectively combat the influenza virus was reported. The SAR results revealed that compound 19b with Boc2-(L)-Lys demonstrated excellent inhibitory activity against A/WSN/33/H1N1 (EC50 = 0.015 µM) and amantadine-resistant strain (A/PR/8/H1N1), low cytotoxicity, high selectivity, substantial degradation ability, and good drug-like properties. Mechanistic studies demonstrated that the proteasome system and autophagic lysosome pathway were the potential drivers of these HyT degraders. Thus, this study provides a powerful tool for investigating the targeted degradation of influenza virus proteins and for antiviral drug development.
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Antiviraux , Interactions hydrophobes et hydrophiles , Thiourée , Antiviraux/pharmacologie , Antiviraux/composition chimique , Antiviraux/synthèse chimique , Humains , Chiens , Animaux , Thiourée/pharmacologie , Thiourée/analogues et dérivés , Thiourée/composition chimique , Relation structure-activité , Sous-type H1N1 du virus de la grippe A/effets des médicaments et des substances chimiques , Cellules rénales canines Madin-Darby , Protéolyse/effets des médicaments et des substances chimiques , Protéines virales/métabolisme , Protéines virales/composition chimique , Protéines virales/antagonistes et inhibiteurs , RNA replicase/antagonistes et inhibiteurs , RNA replicase/métabolisme , Résistance virale aux médicaments/effets des médicaments et des substances chimiquesRÉSUMÉ
The aim of this study was to investigate the effects of acupressure bladder meridian (ABM) on anxiety in rats. Chronic stress was induced rats to establish rat anxiety model. Shuttle experiment and open field experiments of were used to measure behaviors. The levels of cytokines in serum and hippocampus of rats were detected. Brain neurotransmitters (dopamine, 5- hydroxy tryptamine, norepinephrine) were detected by Enzyme linked immunosorbent assay (ELISA) kits. Immunohistochemistry and western blotting were used to detect MAPK and BDNF signal pathway in hippocampus of rats. ABM significantly improve behaviors, decreased cytokine levels in serum and hippocampus. ABM restored the changes of neurotransmitters and significantly decreased protein expressions of MAPK signal pathway and increased protein expressions of BDNF signal pathway in hippocampus of rats. The results shown that ABM significantly improved anxiety via inhibition of MAPK signal pathway and increased BDNF signal pathway.
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Facteur neurotrophique dérivé du cerveau , Hippocampe , Méridiens , Transduction du signal , Animaux , Mâle , Rats , Acupression/méthodes , Troubles anxieux/thérapie , Troubles anxieux/métabolisme , Facteur neurotrophique dérivé du cerveau/métabolisme , Cytokines/métabolisme , Modèles animaux de maladie humaine , Hippocampe/métabolisme , Système de signalisation des MAP kinases/physiologie , Rat Sprague-Dawley , Transduction du signal/physiologie , Vessie urinaire/métabolismeRÉSUMÉ
The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera, Noctuidae), is a highly polyphagous invasive pest that damages various crops. Pesticide control is the most common and effective strategy to control FAW. In this study, we evaluated the toxicity of metaflumizone and indoxacarb against third-instar FAW larvae using the insecticide-incorporated artificial diet method under laboratory conditions. Both metaflumizone and indoxacarb exhibited substantial toxicity against FAW, with LC50 values of 2.43 and 14.66 mg/L at 72 h, respectively. The sublethal effects of metaflumizone and indoxacarb on parental and F1 generation FAW were investigated by exposing third-instar larvae to LC10 and LC30 concentrations of these insecticides. Sublethal exposure to these two insecticides significantly shortened adult longevity, extended pupal developmental times and led to reduced pupal weight, pupation rates, and adult fecundity in the treated parental generation and F1 generation at LC10 or LC30 concentrations, in comparison to the control group. The larval developmental times were shortened in the parental generation but prolonged in the F1 generation, after being treated with sublethal concentrations of metaflumizone. Furthermore, larvae exposed to LC10 or LC30 concentrations of indoxacarb exhibited elevated activity levels of cytochrome P450 monooxygenase and glutathione S-transferase, which coincides with the observed synergistic effect of piperonyl butoxide and diethyl maleate. In conclusion, the high toxicity and negative impact of metaflumizone and indoxacarb on FAW provided significant implications for the rational utilization of insecticides against this pest.
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Insecticides , Larve , Oxazines , Semicarbazones , Spodoptera , Animaux , Spodoptera/effets des médicaments et des substances chimiques , Spodoptera/croissance et développement , Insecticides/toxicité , Insecticides/pharmacologie , Semicarbazones/pharmacologie , Larve/effets des médicaments et des substances chimiques , Oxazines/toxicité , Longévité/effets des médicaments et des substances chimiques , Fécondité/effets des médicaments et des substances chimiques , Inactivation métaboliqueRÉSUMÉ
BACKGROUND: Interstitial lung disease (ILD) is the most widespread and fatal pulmonary complication of rheumatoid arthritis (RA). Existing knowledge on the prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is inconclusive. Therefore, we designed this review to address this gap. MATERIALS AND METHODS: To find relevant observational studies discussing the prevalence and/or risk factors of RA-ILD, EMBASE, Web of Science, PubMed, and the Cochrane Library were explored. The pooled odds ratios (ORs) / hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with a fixed/ random effects model. While subgroup analysis, meta-regression analysis and sensitivity analysis were carried out to determine the sources of heterogeneity, the I2 statistic was utilized to assess between-studies heterogeneity. Funnel plots and Egger's test were employed to assess publication bias. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, our review was conducted. RESULTS: A total of 56 studies with 11,851 RA-ILD patients were included in this meta-analysis. The pooled prevalence of RA-ILD was 18.7% (95% CI 15.8-21.6) with significant heterogeneity (I2 = 96.4%). The prevalence of RA-ILD was found to be more likely as a result of several identified factors, including male sex (ORs = 1.92 95% CI 1.70-2.16), older age (WMDs = 6.89, 95% CI 3.10-10.67), having a smoking history (ORs =1.91, 95% CI 1.48-2.47), pulmonary comorbidities predicted (HRs = 2.08, 95% CI 1.89-2.30), longer RA duration (ORs = 1.03, 95% CI 1.01-1.05), older age of RA onset (WMDs =4.46, 95% CI 0.63-8.29), positive RF (HRs = 1.15, 95%CI 0.75-1.77; ORs = 2.11, 95%CI 1.65-2.68), positive ACPA (ORs = 2.11, 95%CI 1.65-2.68), higher ESR (ORs = 1.008, 95%CI 1.002-1.014), moderate and high DAS28 (≥3.2) (ORs = 1.87, 95%CI 1.36-2.58), rheumatoid nodules (ORs = 1.87, 95% CI 1.18-2.98), LEF use (ORs = 1.42, 95%CI 1.08-1.87) and steroid use (HRs= 1.70, 1.13-2.55). The use of biological agents was a protective factor (HRs = 0.77, 95% CI 0.69-0.87). CONCLUSION(S): The pooled prevalence of RA-ILD in our study was approximately 18.7%. Furthermore, we identified 13 risk factors for RA-ILD, including male sex, older age, having a smoking history, pulmonary comorbidities, older age of RA onset, longer RA duration, positive RF, positive ACPA, higher ESR, moderate and high DAS28 (≥3.2), rheumatoid nodules, LEF use and steroid use. Additionally, biological agents use was a protective factor.
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Polyarthrite rhumatoïde , Pneumopathies interstitielles , Nodule rhumatoïde , Humains , Mâle , Nodule rhumatoïde/complications , Prévalence , Polyarthrite rhumatoïde/complications , Polyarthrite rhumatoïde/épidémiologie , Facteurs de risque , Pneumopathies interstitielles/épidémiologie , Pneumopathies interstitielles/étiologie , StéroïdesRÉSUMÉ
Molecular docking has been widely applied in the discovery of new sweeteners, yet the interpretation of computational results sometimes remains difficult. Here, the interaction between the T1R2-T1R3 sweet taste receptor and 66 tasting compounds, including 26 sweet, 19 bitter, and 21 sour substances was investigated by batch molecular docking processes. Statistical analysis of the docking results generated two novel methods of interpreting taste properties. Quantitative correlation between relative sweetness (RS) and docking results created a multiparameter model to predict sweetness intensity, whose correlation coefficient r = 0.74 is much higher than r = 0.17 for the linear correlation model between sweetness and binding energy. The improved correlation indicated that docking results besides binding energy contain undiscovered information about the ligand-protein interaction. Qualitative discriminant analysis of different tasting molecules generated an uncorrelated linear discriminant analysis (UDLA) model, which achieved an overall 93.1% accuracy in discriminating the taste of molecules, with specific accuracy for verifying sweet, bitter, and sour compounds reaching 88.0%, 92.1%, and 100%. These unprecedented models provide a unique perspective for interpreting computational results and may inspire future research on sweetener discovery.
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Édulcorants , Goût , Édulcorants/composition chimique , Simulation de docking moléculaire , Récepteurs couplés aux protéines G/métabolisme , Perception du goûtRÉSUMÉ
Norovirus is highly infectious and rapidly transmissible and represents a major pathogen of sporadic cases and outbreaks of acute gastroenteritis worldwide, causing a substantial disease burden. Recent years have witnessed a dramatic increase in norovirus outbreaks in China, significantly higher than in previous years, among which GII norovirus is the predominant prevalent strain. Therefore, rapid norovirus diagnosis is critical for clinical treatment and transmission control. Hence, we developed a molecular assay based on RPA combined with the CRISPER-CAS12a technique targeting the conserved region of the GII norovirus genome, the results of which could be displayed by fluorescence curves and immunochromatographic lateral-flow test strips. The reaction only required approximately 50 min, and the results were visible by the naked eye with a sensitivity reaching 102 copies/µl. Also, our method does not cross-react with other common pathogens that cause intestinal diarrhea. Furthermore, this assay was easy to perform and inexpensive, which could be widely applied for detecting norovirus in settings including medical institutions at all levels, particularly township health centers in low-resource areas.
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Systèmes CRISPR-Cas , Norovirus , Humains , Chine , Diarrhée/diagnostic , Épidémies de maladies , Norovirus/génétiqueRÉSUMÉ
The improvement of biosorption efficiency for selective dye removal in a multi-dye aqueous system has become an increasingly significant research topic. However, the competitive effects of coexisting dyes and the target dye in such systems remain uncertain due to complex interactions between adsorbent and coexisting dyes. Therefore, in this research, response surface methodology (RSM) model was effectively employed to investigate the competitive effects of allura red (AR) and malachite green (MG) on methylene blue (MB) removal in a ternary dye aqueous system using three different parts of rape straw powders. In the current design of RSM, the initial concentrations of AR and MG dyes ranging from 0 mg·L-1 to 500 mg·L-1 were considered as influencing factors, while the removal rates of MB on adsorbents at an initial concentration of 500 mg·L-1 were established as response values. The RSM models exhibited high correlation coefficients with adjusted R2 values of 0.9908 (pith core), 0.9870 (seedpods), and 0.9902 (shells), respectively, indicating a close fitted between predicted and actual values. The proposed models indicated that the perturbation effects of initial AR and MG concentrations were observed on the removal rates of MB by three types of rape straw powders in a ternary dye aqueous system, resulting in a decrease in MB removal rates, particularly at higher initial AR concentration due to stronger competitive effects compared to initial MG concentration. The structures of rape straw powders, including pith core, seedpods and shell, were analyzed using scanning eletron microscoe (SEM), energy dispersive spectroscopy (EDS), N2 physisorption isotherm, frourier transform infared spectroscopy (FTIR), Zeta potential classes and fluorescence spectrum before and after adsorption of MB in various dye aqueous systems. The characteristics of rape straw powders suggested that similar adsorption mechanisms, such as electrostatic attraction, pore diffusion, and group complex formation for MB, AR, and MG, respectively, occurred on the surfaces of adsorbents during their respective adsorption processes. This leads to significant competitive effects on the removal rates of MB in a ternary dye aqueous system, which are particularly influenced by initial AR concentrations as confirmed through fluorescence spectrum analysis.
Impact of AR and MG on MB removal was analyzed using simple methodologies.Competitive behaviors between AR, MG and MB were understood through RSM.Intense restrain effects on MB removal were revealed by AR concentration.
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Dépollution biologique de l'environnement , Agents colorants , Bleu de méthylène , Poudres , Polluants chimiques de l'eau , Adsorption , Agents colorants/composition chimique , Magenta I/composition chimique , Brassica rapa , Composés azoïques , Élimination des déchets liquides/méthodesRÉSUMÉ
Rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS) are the most common systemic autoimmune diseases, and they are increasingly being recognized as occurring in the same patient population. These two diseases share several clinical features and laboratory parameters, but the exact mechanism of their co-pathogenesis remains unclear. The intention of this study was to investigate the common molecular mechanisms involved in RA and pSS using integrated bioinformatic analysis. RNA-seq data for RA and pSS were picked up from the Gene Expression Omnibus (GEO) database. Co-expression genes linked with RA and pSS were recognized using weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. Then, we screened two public disease-gene interaction databases (GeneCards and Comparative Toxicogenomics Database) for common targets associated with RA and pSS. The DGIdb database was used to predict therapeutic drugs for RA and pSS. The Human microRNA Disease Database (HMDD) was used to screen out the common microRNAs associated with RA and pSS. Finally, a common miRNA-gene network was created using Cytoscape. Four hub genes (CXCL10, GZMA, ITGA4, and PSMB9) were obtained from the intersection of common genes from WGCNA, differential gene analysis and public databases. Twenty-four drugs corresponding to hub gene targets were predicted in the DGIdb database. Among the 24 drugs, five drugs had already been reported for the treatment of RA and pSS. Other drugs, such as bortezomib, carfilzomib, oprozomib, cyclosporine and zidovudine, may be ideal drugs for the future treatment of RA patients with pSS. According to the miRNA-gene network, hsa-mir-21 may play a significant role in the mechanisms shared by RA and pSS. In conclusion, we identified commom targets as potential biomarkers in RA and pSS from publicly available databases and predicted potential drugs based on the targets. A new understanding of the molecular mechanisms associated with RA and pSS is provided according to the miRNA-gene network.
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Polyarthrite rhumatoïde , microARN , Syndrome de Gougerot-Sjögren , Humains , Syndrome de Gougerot-Sjögren/traitement médicamenteux , Syndrome de Gougerot-Sjögren/génétique , Polyarthrite rhumatoïde/traitement médicamenteux , Polyarthrite rhumatoïde/génétique , microARN/génétique , Analyse de profil d'expression de gènes , Réseaux de régulation géniqueRÉSUMÉ
Estrogen receptor (ER) ß and histone deacetylases (HDACs), when overexpressed, are associated closely with the occurrence and development of prostate cancer and are, therefore, considered important targets and biomarkers used in the clinical treatment of prostate cancer. The present study involved the design and synthesis of the first ERß and HDAC dual-target near-infrared fluorescent probe with both imaging capacity and antitumor activity for prostate cancer. Both P1 and P2 probes exhibited excellent ERß selectivity, with P1 being almost exclusively selective for ERß compared to ERα. In addition, P1 exhibited good optical properties, such as strong near-infrared emission, large Stokes shift, and better anti-interference ability, along with excellent imaging ability for living cells. P1 also exhibited potent inhibitory activity against HDAC6 and DU-145 cells, with IC50 values of 52 nM and 0.96 µM, respectively. Further, P1 was applied successfully for the in vivo imaging of prostate cancer in a mouse model, and significant in vivo antitumor efficacy was achieved. The developed dual-target NIR fluorescent probe is expected to serve as an effective tool in the research on prostate cancer, leading to novel insights for the theranostic study of diseases related to ERß and HDACs.