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In the field of nonlinear optical (NLO) materials research, the design and synthesis of novel materials are crucial for advancing modern scientific and technological development. This study employs an innovative coordination strategy, building upon the existing structure of [Ln2(CH3COO)6(H2O)4]·4H2O (Ln = Tb, Sm), to successfully synthesize a series of acetate rare-earth metal compounds [Ln2(CH3COO)6(H2O)]n [Ln = Tb(1), Er(2), Y(3)] by regulating the number of water molecules. This approach achieved a structural transition from centrosymmetric (CS) to noncentrosymmetric (NCS), endowing these compounds with significant nonlinear optical responses. We discovered that reducing the coordinated water molecules and introducing acetate as a bidentate ligand is an effective method for modulating crystal structure and realizing NLO performance. This finding not only deepens the understanding of the structure of acetate salts but also provides important theoretical and experimental support for the development of materials with potential NLO propeties.
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Natural volatile organic compounds (NVOCs) and airborne microorganisms are important elements in urban forest air that affect air quality and human health. In this study, the Zhuyu Bay urban forest in Yangzhou was selected as the research object, and gas chromatography-mass spectrometry (GC-MS) was used to detect the composition of NVOCs in different forest stands. Terpenes, heterocyclic compounds, and esters accounted for the highest proportions. We then explored the effects of NVOCs on the physiological health of each forest stand and used Kyoto Encyclopedia of Genes and Genome enrichment analysis to identify beneficial secondary metabolites. Among the identified compounds, alpha-phellandrene 1, azulene, and other terpenoids were found to possess antibacterial, anti-inflammatory, and antioxidant properties. Heterocyclic compounds, such as 4-Pyridinecarboxylic acid and visnagin, showed significant effects in the treatment of diseases. In addition, we collected and analyzed culturable airborne microorganisms in different forest stands and found that the bamboo forest had the lowest number of culturable airborne microorganisms. To further explore the influence of urban microclimates on air microorganisms and NVOCs, a partial least squares path modelling (PLS-PM) analysis was conducted. Air negative oxygen ion is an important factor affecting NVOCs, and Air moisture has a significant positive effect on bacteria proportion.
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Background: This study aims to observe the relationship between novel inflammatory markers and AMI, and analyze its correlation with the degree of coronary artery disease. Methods: Clinical data were collected from the control (510 cases) and AMI (406 cases) groups. The AMI group was classified into mild, moderate and severe according to the Gensini score. Correlation of SII, SIRI, MHR and NHR with Gensini score in AMI patients was analysed using Spearman rank correlation analysis. Factors influencing the degree of coronary lesion in AMI were analysed by multi-factor ordinal logistic regression. The predictive value of the novel inflammatory markers for AMI and its coronary severity was assessed using ROC curves. Risk prediction of the extent of coronary artery disease in AMI using the Nomogram for novel inflammatory indices. Results: The levels of SII, SIRI, MHR and NHR were significantly higher in the AMI group than in the control group. With increasing Gensini score, all four novel inflammatory indices showed an increasing trend. And four novel inflammatory indices were positively correlated with Gensini scores. Meanwhile, SII, SIRI and MHR were independent risk factors for the extent of coronary artery disease in AMI. SII, SIRI, MHR and NHR have good predictive value for AMI, and have predictive value for mild and severe AMI, but have no predictive value for moderate AMI. The nomogram results showed that SII, SIRI and MHR had some predictive value for the degree of coronary artery disease in AMI. The nomogram results showed that SII, SIRI and MHR had some predictive value for the degree of coronary artery disease in AMI. Conclusion: The elevated levels of SIRI, SII, MHR, NHR in AMI patients are independent risk factors for the severity of coronary artery disease in AMI patients, and have predictive value to a certain extent.
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Currently, scientifically and reasonably specifying carbon emission reduction measures in the context of "double carbon" has become a common concern worldwide. China's administrative divisions have a notable impact on the formulation and implementation of relevant policies. Therefore the carbon emissions must be calculated accurately under China's administrative divisions at different scales. The spatiotemporal change characteristics of absorption and carbon emissions can provide scientific basis for the formulation of reasonable and differentiated carbon emission reduction policies in different administrative regions in China. To this end, this study used multi-source data such as remote sensing and statistics and integrated ecological models, statistics, and GIS space analysis and other methods to analyze the spatiotemporal dynamic change characteristics of carbon emissions and carbon absorption at different administrative scales ï¼provinces, cities, and countiesï¼ in China. The results showed thatï¼ â The total carbon absorption of vegetation in China continued to increase from 2000 to 2021 and the average value gradually increased. Differences were observed in spatiotemporal changes in carbon emissions at different administrative scales. The spatiotemporal changes at smaller scales were more evident. Carbon emissions showed obvious spatial differences of "high in the north and low in the south, high in the east and low in the west." â¡ The spatiotemporal distribution of CPI at the administrative scale was similar to that of carbon emissions and the overall trend was increasing annually. The pressure of carbon emissions on carbon absorption gradually weakened from the east to the central and western regions. ⢠Spatiotemporal hotspot analysis showed that the overall spatial distribution of cold and hot spots in China's carbon absorption was as followsï¼ In the spatial pattern of "hot in the east and cold in the west," the spatial distribution of cold and hot spots of carbon emissions showed agglomeration characteristics. The provincial scale was primarily oscillating hotspot whereas municipal and county scales were majorly continuous hot spots. Further results revealed thatï¼ â Carbon absorption in different regions and periods in China showed significant variability, especially in the central and eastern regions. The possibility of offsetting carbon emissions by increasing carbon absorption remains. â¡ At the same scale, administrative regions ï¼such as different provincesï¼ and lower-level administrative regions at another scale ï¼such as different cities in the same provinceï¼ showed varying degrees of variability in carbon absorption and carbon emissions. Therefore, taking provincial administrative regions as an example for subsequent formulation considering carbon trading, emission reduction, and other policies, we should first consider the coordination of emissions between different cities in the province and then consider the coordination between provinces, which is expected to better promote the implementation of relevant policies.
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In order to increase the suitability of coarse recycled concrete aggregates and improve the frost resistance of recycled coarse aggregate concrete, this study aims to investigate the effects of an antifreeze-type water-reducing admixture, air-entraining admixture, and antifreeze admixture on the frost resistance of recycled coarse aggregate concrete. The effectiveness of these admixtures is gauged by the mass loss rate and the relative dynamic modulus of elasticity (RDM). Mercury-impressed porosimetry (MIP), super depth of field microscopy, and scanning electron microscopy (SEM) were employed to characterize the hydration products, microstructure, and pore structure of recycled coarse aggregate concrete, with a view to establishing a connection between the microstructural characteristics and the macro properties and analyzing the micro-mechanism of the improvement effect of frost resistance. The test results demonstrate that the admixtures have a significant impact on the frost resistance of recycled coarse aggregate concrete. In particular, the recycled coarse aggregate concrete with an antifreeze admixture (dosage of 1%) and a water-cement ratio of 0.41 exhibited a mass loss of only 1.23% after 200 freezing and thawing cycles, a relative dynamic modulus of elasticity of up to 93.97%; however, the control group had reached the stopping condition at 150 freeze-thaw cycles with more than 10% mass loss. The recycled coarse aggregate concrete with added antifreeze admixture had a tight connection between the aggregate and the paste and a more pronounced improvement in the pore structure, indicating excellent resistance to frost damage.
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TBK1 is an important IFN antiviral signalling factor, and in previous work black carp TBK1 (bcTBK1) and black carp IRF5 (bcIRF5) together promoted cell death in GCRV-infected cells. In this research, bcTBK1 and bcIRF5 were investigated both in vivo and in vitro to delineate their individual and combined functions. This study demonstrated that both bcTBK1 and bcIRF5 expressions were modulated in response to GCRV infection across the intestine, gill, kidney and spleen. In bcgill cells, overexpression of bcTBK1 and bcIRF5 initially suppressed the expression of cell death-related genes, including RIPK1, caspase1, caspase3 and bax, but this suppression was negated upon GCRV infection. In vivo, mRNA expression levels of RIPK1 and related genes varied by tissue following bcTBK1 or bcIRF5 overexpression and GCRV infection. Notably, intracellular co-overexpression of bcTBK1 and bcIRF5 led to significant upregulation of caspase3, caspase1, bax, and IL1ß, along with enhanced caspase3 activity post-GCRV infection. This co-expression correlated with higher survival rates in black carp during GCRV infection and increased caspase3 mRNA in the spleen and gills. Hematoxylin-eosin (HE) staining indicated disorganized spleen tissue and edematous, hyperplastic gill changes in co-transfected groups after infection. TUNEL staining of tissue sections showed that DNA breakage was significantly stronger in the co-transfected group than in the other groups during GCRV infection. Further phosphorylation experiments showed that bcIRF5 promoted phosphorylation modification of bcTBK1. Thus, these data suggest that bcIRF5 activates bcTBK1 by enhancing its phosphorylation and promotes PANoptosis in GCRV-infected cells.
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c-Src is involved in multiple signaling pathways and serves as a critical target in various cancers. Growing evidence suggests that prolonging a drug's residence time (RT) can enhance its efficacy and selectivity. Thus, the development of c-Src antagonists with longer residence time could potentially improve therapeutic outcomes. In this study, we employed molecular dynamics simulations to explore the binding modes and dissociation processes of c-Src with antagonists characterized by either long or short RTs. Our results reveal that the long RT compound DAS-DFGO-I (DFGO) occupies an allosteric site, forming hydrogen bonds with residues E310 and D404 and engaging in hydrophobic interactions with residues such as L322 and V377. These interactions significantly contribute to the long RT of DFGO. However, the hydrogen bonds between the amide group of DFGO and residues E310 and D404 are unstable. Substituting the amide group with a sulfonamide yielded a new compound, DFOGS, which exhibited more stable hydrogen bonds with E310 and D404, thereby increasing its binding stability with c-Src. These results provide theoretical guidance for the rational design of long residence time c-Src inhibitors to improve selectivity and efficacy.
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Enlace de Hidrógeno , Simulación de Dinámica Molecular , Inhibidores de Proteínas Quinasas , Humanos , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Proteína Tirosina Quinasa CSK/química , Proteína Tirosina Quinasa CSK/metabolismo , Familia-src Quinasas/antagonistas & inhibidores , Familia-src Quinasas/química , Familia-src Quinasas/metabolismo , Unión Proteica , Interacciones Hidrofóbicas e Hidrofílicas , Sitio Alostérico , Sitios de UniónRESUMEN
Background: Emerging research suggests the relationship between the oral microbiome and sleep duration with depression, however, the precise mechanisms by which oral microbial diversity influences the sleep-depression nexus remain to be elucidated. Methods: We analyzed data from 4,692 participants in the National Health and Nutrition Examination Survey (NHANES), incorporating key demographic variables, oral microbiome diversity metrics, sleep duration, and depression assessment variables. Classical multidimensional scaling facilitated dimensionality reduction, while unsupervised clustering divided participants into groups based on ß-diversity dissimilarity matrices. We examined the moderating effects of oral microbiome diversity on the sleep-depression relationship by incorporating interaction terms sleep-oral microbiome diversity into multiple linear regression models. Results: Our analysis revealed a U-shaped relationship between sleep duration and depression. Specifically, α-diversity was a significant moderator, with reduced diversity linked to an increased depression risk in participants with insufficient sleep. Regarding ß-diversity, using both Bray-Curtis and UniFrac distance measures, Cluster 2 exhibited the strongest associations in sleep-deprived individuals (Bray-Curtis: ß = 1.02, p < 0.001; Weighted UniFrac: ß = 0.91, p < 0.001). In contrast, Cluster 1 displayed notable effects in individuals with excessive sleep (Bray-Curtis: ß = 0.63, p = 0.008). Additionally, Cluster 3 was prominently associated with depression in sleep-deprived participants using unweighted UniFrac distance (ß = 0.93, p < 0.001), and Cluster 2 was significant among those with excessive sleep across both unweighted (ß = 0.80, p = 0.0004) and weighted UniFrac distances (ß = 0.60, p = 0.001). Conclusion: This study highlights the crucial role of oral microbiome diversity in moderating the U-shaped relationship between sleep duration and depression risk.
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Spontaneous forward-reverse mutations were reported by us earlier in clinical samples from various types of cancers and in HeLa cells under normal culture conditions. To investigate the effects of chemical stimulations on such mutation cycles, the present study examined single nucleotide variations (SNVs) and copy number variations (CNVs) in HeLa and A549 cells exposed to wogonin-containing or acidic medium. In wogonin, both cell lines showed a mutation cycle during days 16-18. In acidic medium, both cell lines displayed multiple mutation cycles of different magnitudes. Genomic feature colocalization analysis suggests that CNVs tend to occur in expanded and unstable regions, and near promoters, histones, and non-coding transcription sites. Moreover, phenotypic variations in cell morphology occurred during the forward-reverse mutation cycles under both types of chemical treatments. In conclusion, chemical stresses imposed by wogonin or acidity promoted cyclic forward-reverse mutations in both HeLa and A549 cells to different extents.
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Variaciones en el Número de Copia de ADN , Flavanonas , Mutación , Humanos , Células HeLa , Flavanonas/farmacología , Variaciones en el Número de Copia de ADN/genética , Mutación/genética , Células A549 , Polimorfismo de Nucleótido Simple/genética , Neoplasias/genética , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Línea Celular TumoralRESUMEN
Pyrethroids serve as a significant method for managing and preventing parasitic diseases in fish. Among these, deltamethrin (DEL) is used extensively in aquatic environments. Our previous work has been confirmed that DEL exposure can induce oxidative stress and immunosuppression on the gill mucosal barrier of crucian carp (Carassius auratus). However, it is not clear whether DEL affects the susceptibility of farmed fish to bacterial infection. In this study, fish was pre-exposed to different DEL concentration (0, 0.3 and 0.6 µg L-1) and then challenged by immersion with Aeromonas hydrophila (1.0 × 10^8 CFU mL-1). After immersion challenge, fish pre-exposed to DEL developed prominent lipopolysaccharides level in gill and serum and had a significantly lower survival rate compared to the control group. In DEL pre-exposure fish after immersion, the gill apoptosis levels were significantly higher and disrupted the tight junction barrier by downregulating the zo1 and claudin12. Furthermore, fish pre-exposed to DEL exhibited increased activities of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and malonaldehyde (MDA) levels in the early stage after immersion but experiencing decreased activities of glutathione peroxidase (GPx) and lysozyme (LZM) in the later stage after immersion. And this process was regulated by the NRF2 pathway. Additionally, fish pre-exposed to DEL after immersion had significantly lower mRNA levels of immune-related genes tlr4, myd88, tnfα, and il-1ß. Overall, these findings indicate that DEL damaged the gill barrier, weakened the immune response, raised LPS levels, and heightened vulnerability to A. hydrophila infection in crucian carp, resulting in mortality. Thus, this work will help social groups and aquaculture workers to understand the potential risk of DEL exposure for bacterial secondary infection in cultured fish.
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Aeromonas hydrophila , Carpas , Branquias , Nitrilos , Piretrinas , Animales , Aeromonas hydrophila/fisiología , Piretrinas/toxicidad , Branquias/efectos de los fármacos , Nitrilos/toxicidad , Enfermedades de los Peces/microbiología , Estrés Oxidativo/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Contaminantes Químicos del Agua/toxicidad , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/inmunologíaRESUMEN
Xanthine oxidase (XO) is an important enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid in the catabolism of purines in humans. This makes XO a well-recognized target in alleviating hyperuricemia. The present study adapted a structure-based drug discovery approach to develop potent and low-toxicity XO inhibitors with the chalcone skeleton. We introduced a carboxyl group and a hydroxyl group to the B ring and modified the A ring. 35 chalcone derivatives were designed and synthesized. All the 35 derivatives exhibited higher XO inhibition activities (IC50 = 0.064-0.559 µM) compared with allopurinol (IC50 = 2.588 µM). Their high affinity was attributed to strong hydrogen bond interactions formed between the introduced carboxyl and hydroxyl groups with key amino acid residues in XO. SAR analysis disclosed that carboxyl, hydroxyl, ethyl (12c), methylamino (12h), dimethylamino (12i), indolin (13k), and indol (13l) groups played important roles in improving the whole molecules' inhibition potency against XO. ADME predictions and cytotoxicity assays suggested their pharmacokinetic characteristics and biocompatibility were desirable. Additionally, 12c exhibited a significant hypouricemic effect on potassium oxonate-induced hyperuricemia rats after orally administrated at a dose range of 10-40 mg/kg, representing a promising anti-hyperuricemia potential for further optimization and development.
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Diseño de Fármacos , Inhibidores Enzimáticos , Xantina Oxidasa , Xantina Oxidasa/antagonistas & inhibidores , Xantina Oxidasa/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Relación Estructura-Actividad , Animales , Ratas , Humanos , Estructura Molecular , Relación Dosis-Respuesta a Droga , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/inducido químicamente , Masculino , Chalconas/farmacología , Chalconas/química , Chalconas/síntesis química , Ratas Sprague-Dawley , Chalcona/farmacología , Chalcona/química , Chalcona/síntesis química , Simulación del Acoplamiento MolecularRESUMEN
The discovery and designed synthesis of multifunctional materials is a leading pursuit in materials science. Herein, we report a novel hydro-isocyanurate, N2H4Zn(HC3N3O3), which combines strong second harmonic generation (SHG) and ultra-long room-temperature phosphorescence (RTP). The SHG intensity is the highest within the cyanurate system (13 × KDP), and RTP lifetime extends up to 448 ms, accompanied by a long-lasting afterglow visible to the naked eye for 1.2 s, surpassing most of the current metal-organic complexes. This advancement holds promise for the development of multifunctional optoelectronic devices, particularly leveraging second-harmonic generation (SHG) processes.
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With the development of educational technology, machine learning and deep learning provide technical support for traditional classroom observation assessment. However, in real classroom scenarios, the technique faces challenges such as lack of clarity of raw images, complexity of datasets, multi-target detection errors, and complexity of character interactions. Based on the above problems, a student classroom behavior recognition network incorporating super-resolution and target detection is proposed. To cope with the problem of unclear original images in the classroom scenario, SRGAN (Super Resolution Generative Adversarial Network for Images) is used to improve the image resolution and thus the recognition accuracy. To address the dataset complexity and multi-targeting problems, feature extraction is optimized, and multi-scale feature recognition is enhanced by introducing AKConv and LASK attention mechanisms into the Backbone module of the YOLOv8s algorithm. To improve the character interaction complexity problem, the CBAM attention mechanism is integrated to enhance the recognition of important feature channels and spatial regions. Experiments show that it can detect six behaviors of students-raising their hands, reading, writing, playing on their cell phones, looking down, and leaning on the table-in high-definition images. And the accuracy and robustness of this network is verified. Compared with small-object detection algorithms such as Faster R-CNN, YOLOv5, and YOLOv8s, this network demonstrates good detection performance on low-resolution small objects, complex datasets with numerous targets, occlusion, and overlapping students.
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PROPOSE: This study aims to present long-term outcomes in a specific patient population experiencing epiphora due to low-level nasolacrimal duct obstruction (NLDO) following endonasal endoscopic nasolacrimal duct rhinostomy, and to propose a surgical selection paradigm for varying locations of NLDO. METHODS: Between September 1, 2017 and February 28, 2023, a retrospective analysis was conducted on 26 patients diagnosed with primary acquired nasolacrimal duct obstruction (PANDO) who underwent endonasal endoscopic nasolacrimal duct rhinostomy for low-level NLDO (defined as obstruction below the plane of the superior border of the inferior turbinate attachment). The study assessed surgical success through objective measures of anatomical patency and subjective measures of functional patency during a postoperative follow-up period of at least six months. Additionally, any complications that arose during this follow-up period were documented. RESULTS: The study included a cohort of 26 patients, consisting of 24 women and 2 men, with a mean age of 47.58 ± 3.09 years (range: 8-75). All patients underwent endoscopic nasolacrimal duct rhinostomy, with 10 eyes having previously undergone tear duct recanalization procedures. Anatomical patency was achieved in 88.5% (23/26) of cases, while functional patency was achieved in 80.8% (21/26) after an average follow-up period of 41.9 ± 22.1 months. No significant complications were observed in any of the patients during the follow-up period. CONCLUSION: Endonasal endoscopic nasolacrimal duct rhinostomy is effective in treating epiphora in over 80% of cases with low-level NLDO. Tailoring the surgery to the location of the obstruction can improve outcomes and minimize damage.
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Dacriocistorrinostomía , Obstrucción del Conducto Lagrimal , Conducto Nasolagrimal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Conducto Nasolagrimal/cirugía , Adulto , Anciano , Dacriocistorrinostomía/métodos , Resultado del Tratamiento , Endoscopía/métodos , Estudios de SeguimientoRESUMEN
IkappaB kinase beta (IKKß) is a key member of IκB kinases and functions importantly in interferon (IFN) signaling. Phosphorylation and ubiquitination are involved in the activation of IKKß. A20 is a de-ubiquitin enzyme and functions as a suppressor in inflammation signaling, which has been reported to be phosphorylated and activated by IKKß. However, the role and relationship of IKKß and A20 in teleost remains unclear. In this study, IKKß (bcIKKß) and A20 (bcA20) of black carp (Mylopharyngodon piceus) have been cloned and characterized. Overexpressed bcIKKß in EPC cells showed strong anti-viral ability by activating both NF-κB and IFN signaling. EPC cells stable expressing bcIKKß presented improved anti-viral activity as well. The interaction between bcA20 and bcIKKß was identified, and overexpression of bcA20 was able to suppress bcIKKß-mediated activation of NF-κB and IFN signaling. Meanwhile, knock-down of A20 increased host the antiviral ability of host cells. Importantly, it has been identified that bcA20 was able to remove K27-linked ubiquitination and decrease the phosphorylation of bcIKKß. Thus, our data conclude that bcA20 suppresses the anti-viral activity of bcIKKß and removes its K27-linked ubiquitination, which presents a new mechanism of IKKß regulation.
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Carpas , Proteínas de Peces , Quinasa I-kappa B , Transducción de Señal , Ubiquitinación , Animales , Quinasa I-kappa B/genética , Quinasa I-kappa B/inmunología , Quinasa I-kappa B/metabolismo , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Proteínas de Peces/química , Carpas/inmunología , Carpas/genética , Transducción de Señal/inmunología , Interferones/genética , Interferones/inmunología , Interferones/metabolismo , Enfermedades de los Peces/inmunología , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/inmunología , Inmunidad Innata/genética , Regulación de la Expresión Génica/inmunología , Alineación de Secuencia/veterinaria , Filogenia , Perfilación de la Expresión Génica/veterinaria , Secuencia de AminoácidosRESUMEN
A Mn-catalyzed ligand-directed Csp3-Csp2 coupling of tertiary allylic alcohols with arylaldehydes has been developed. The method provides an efficient approach to access 1,5-diarylpent-1-en-3-ones via carbon-skeleton rearrangement-based aldol reaction.
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Peripheral nerve injury (PNI) poses a significant public health issue, often leading to muscle atrophy and persistent neuropathic pain, which can drastically impact the quality of life for patients. Electrical stimulation represents an effective and non-pharmacological treatment to promote nerve regeneration. Yet, the postoperative application of electrical stimulation remains a challenge. Here, we propose a fully biodegradable, self-powered nerve guidance conduit (NGC) based on dissolvable zinc-molybdenum batteries. The conduit can offer topographic guidance for nerve regeneration and deliver sustained electrical cues between both ends of a transected nerve stump, extending beyond the surgical window. Schwann cell proliferation and adenosine triphosphate (ATP) production are enhanced by the introduction of the zinc-molybdenum batteries. In rodent models with 10-mm sciatic nerve damage, the device effectively enhances nerve regeneration and motor function recovery. This study offers innovative strategies for creating biodegradable and electroactive devices that hold important promise to optimize therapeutic outcomes for nerve regeneration.
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Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Nervio Ciático , Zinc , Animales , Traumatismos de los Nervios Periféricos/terapia , Zinc/química , Nervio Ciático/fisiología , Nervio Ciático/lesiones , Ratas , Suministros de Energía Eléctrica , Molibdeno/química , Células de Schwann , Ratas Sprague-Dawley , Humanos , Regeneración Tisular Dirigida/instrumentación , Regeneración Tisular Dirigida/métodos , Técnicas Biosensibles , Implantes AbsorbiblesRESUMEN
Mendelian randomization (MR), which utilizes genetic variants as instrumental variables (IVs), has gained popularity as a method for causal inference between phenotypes using genetic data. While efforts have been made to relax IV assumptions and develop new methods for causal inference in the presence of invalid IVs due to confounding, the reliability of MR methods in real-world applications remains uncertain. Instead of using simulated datasets, we conducted a benchmark study evaluating 16 two-sample summary-level MR methods using real-world genetic datasets to provide guidelines for the best practices. Our study focused on the following crucial aspects: type I error control in the presence of various confounding scenarios (e.g., population stratification, pleiotropy, and family-level confounders like assortative mating), the accuracy of causal effect estimates, replicability, and power. By comprehensively evaluating the performance of compared methods over one thousand exposure-outcome trait pairs, our study not only provides valuable insights into the performance and limitations of the compared methods but also offers practical guidance for researchers to choose appropriate MR methods for causal inference.
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Benchmarking , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Análisis de la Aleatorización Mendeliana/métodos , Humanos , Estudio de Asociación del Genoma Completo/métodos , Fenotipo , Variación Genética , Causalidad , Polimorfismo de Nucleótido Simple , Modelos GenéticosRESUMEN
Semihydrogenation is a crucial industrial process. Noble metals such as Pd have been extensively studied in semihydrogenation reactions, owing to their unique catalytic activity toward hydrogen activation. However, the overhydrogenation of alkenes to alkanes often happens due to the rather strong adsorption of alkenes on Pd active phases. Herein, we demonstrate that the incorporation of Pd active phases as single-atom sites in perovskite lattices such as SrTiO3 can greatly alternate the electronic structure and coordination environment of Pd active phases to facilitate the desorption of alkenes rather than further hydrogenation. Furthermore, the incorporated Pd sites can be well stabilized without sintering by a strong host-guest interaction with SrTiO3 during the activation of H species in hydrogenation reactions. As a result, the Pd incorporated SrTiO3 (Pd-SrTiO3) exhibits an excellent time-independent selectivity (>99.9 %) and robust durability for the photocatalytic semihydrogenation of phenylacetylene to styrene. This strategy based on incorporation of active phases in perovskite lattices will have broad implications in the development of high-performance photocatalysts for selective hydrogenation reactions.
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Optoelectronic neural interfaces can leverage the photovoltaic effect to convert light into electrical current, inducing charge redistribution and enabling nerve stimulation. This method offers a non-genetic and remote approach for neuromodulation. Developing biodegradable and efficient optoelectronic neural interfaces is important for achieving transdermal stimulation while minimizing infection risks associated with device retrieval, thereby maximizing therapeutic outcomes. We propose a biodegradable, flexible, and miniaturized silicon-based neural interface capable of transdermal optoelectronic stimulation for neural modulation and nerve regeneration. Enhancing the device interface with thin-film molybdenum significantly improves the efficacy of neural stimulation. Our study demonstrates successful activation of the sciatic nerve in rodents and the facial nerve in rabbits. Moreover, transdermal optoelectronic stimulation accelerates the functional recovery of injured facial nerves.