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Foreign ions as additives are of great significance for realizing excellent control over the morphology of noble metal nanostructures in the state-of-the-art seed-mediated growth method; however, they remain largely unexplored in chiral synthesis. Here, we report on a Cu2+-dominated chiral growth strategy that can direct the growth of concave chiral Au nanoparticles with C3-dominant chiral centers. The introduction of trace amounts of Cu2+ ions in the seed-mediated chiral growth process is found to dominate the chirality transfer from chiral molecules to chiral nanoparticles, leading to the formation of chiral nanoparticles with a concave VC geometry. Both experimental and theoretical results further demonstrate the correlation between the nanoparticle structure and optical chirality for the concave chiral nanoparticle. The Cu2+ ion is found to dominate the chiral growth by selectively activating the deposition of Au atoms along the [110] and [111] directions, facilitating the formation of the concave VC. We further demonstrate that the Cu2+-dominated chiral growth strategy can be employed to generate a variety of concave chiral nanoparticles with enriched geometric chirality and desired chiroptical properties. Concave chiral nanoparticles also exhibit appealing catalytic activity and selectivity toward electrocatalytic oxidation of enantiomers in comparison to helicoidal nanoparticles. The ability to tune the geometric chirality in a controlled manner by simply manipulating the Cu2+ ions as additives opens up a promising strategy for creating chiral nanomaterials with increasing architectural diversity for chirality-dependent optical and catalytic applications.
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Stroke is an acute injury of the central nervous system caused by the disorders of cerebral blood circulation, which has become one of the major causes of disability and death. Hemorrhage, particularly subarachnoid hemorrhage (SAH), is one of the poorest prognostic factors in stroke, which is related to the thrombolytic therapy, and has been considered very dangerous. In this context, the MR angiography with high sensitivity and resolution has been developed based on biocompatible paramagnetic ultrasmall NaGdF4 nanoprobes. Owing to the appropriate hydrodynamic diameter, the nanoprobe can be confined inside the blood vessels and it only extravasates at the vascular injury site when the bleeding occurs. Relying on this property, the three-dimensional (3D) anatomic structures of artery occlusion of stroke rat can be precisely visualized; reperfusion-related SAH has been successfully visualized and identified. Benefiting from the long blood half-life of the nanoprobe, the observation window of MR angiography can last for the whole period of reperfusion, thereby monitoring the probable SAH in real time during thrombolytic therapy. More importantly, through reconstruction of multiparametric MRI, the arterial occlusion, cerebral ischemic region, and SAH can be simultaneously visualized in vivo in a 3D manner for the first time. Therefore, the current study provides a novel approach for both noninvasive 3D vascular visualization and hemorrhage alert, which possesses great prospects for clinical translation.
Assuntos
AVC Isquêmico , Angiografia por Ressonância Magnética , Hemorragia Subaracnóidea , Animais , Hemorragia Subaracnóidea/diagnóstico por imagem , Ratos , AVC Isquêmico/diagnóstico por imagem , Ratos Sprague-Dawley , Masculino , Gadolínio/química , ReperfusãoRESUMO
Integrating the plasmonic chirality with excellent catalytic activities in plasmonic hybrid nanostructures provides a promising strategy to realize the chiral nanocatalysis toward many chemical reactions. However, the controllable synthesis of catalytically active chiral plasmonic nanoparticles with tailored geometries and compositions remains a significant challenge. Here it is demonstrated that chiral Au-Pd alloy nanorods with tunable optical chirality and catalytically active surfaces can be achieved by a seed-mediated coreduction growth method. Through manipulating the chiral inducers, Au nanorods selectively transform into two different intrinsically chiral Au-Pd alloy nanorods with distinct geometric chirality and tunable optical chirality. By further adjusting several key synthetic parameters, the optical chirality, composition, and geometry of the chiral Au-Pd nanorods are fine-tailored. More importantly, the chiral Au-Pd alloy nanorods exhibit appealing chiral catalytic activities as well as polarization-dependent plasmon-enhanced nanozyme catalytic activity, which has great potential for chiral nanocatalysis and plasmon-induced chiral photochemistry.
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Hypernetwork is a useful way to depict multiple connections between nodes, making it an ideal tool for representing complex relationships in network science. In recent years, there has been a marked increase in studies on hypernetworks; however, the comparison of the difference between two hypernetworks has received less attention. This paper proposes a hyper-distance (HD)-based method for comparing hypernetworks. The method is based on higher-order information, i.e, the higher-order distance between nodes and Jensen-Shannon divergence. Experiments carried out on synthetic hypernetworks have shown that HD is capable of distinguishing between hypernetworks generated with different parameters, and it is successful in the classification of hypernetworks. Furthermore, HD outperforms current state-of-the-art baselines to distinguish empirical hypernetworks when hyperedges are randomly perturbed.
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Three series of N-{[4-([1,2,4]triazolo[1,5-α]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]methyl}acetamides (14a-d, 15a-n, and 16a-f) were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. The target compounds showed high ALK5 inhibitory activity and selectivity. The half maximal inhibitory concentration (IC50) for phosphorylation of ALK5 of 16f (9.1 nM), the most potent compound, was 2.7 times that of the clinical candidate EW-7197 (vactosertib) and 14 times that of the clinical candidate LY-2157299. The selectivity index of 16f against p38α mitogen-activated protein kinase was >109, which was much higher than that of positive controls (EW-7197: >41, and LY-2157299: 4). Furthermore, a molecular docking study provided the interaction modes between the target compounds and ALK5. Compounds 14c, 14d, and 16f effectively inhibited the protein expression of α-smooth muscle actin (α-SMA), collagen I, and tissue inhibitor of metalloproteinase 1 (TIMP-1)/matrix metalloproteinase 13 (MMP-13) in transforming growth factor-ß-induced human umbilical vein endothelial cells. Compounds 14c and 16f showed especially high activity at low concentrations, which suggests that these compounds could inhibit myocardial cell fibrosis. Compounds 14c, 14d, and 16f are potential preclinical candidates for the treatment of cardiac fibrosis.
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Fibrose , Imidazóis , Simulação de Acoplamento Molecular , Receptor do Fator de Crescimento Transformador beta Tipo I , Humanos , Imidazóis/farmacologia , Imidazóis/síntese química , Imidazóis/química , Relação Estrutura-Atividade , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Fibrose/tratamento farmacológico , Estrutura Molecular , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Antifibróticos/farmacologia , Antifibróticos/síntese química , Antifibróticos/química , Amidas/farmacologia , Amidas/síntese química , Amidas/química , Relação Dose-Resposta a Droga , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
Conjugation with the increment of consumption of polypropylene (PP) masks and antidepressants during pandemic, PP microplastics (MPs) and Venlafaxine (VEN) widely co-existed in surface waters. However, their environmental fate and the combined toxicity were unclear. Hence, we investigated the adsorption behaviors, and associated mechanisms of PP MPs for VEN. The impact factors including pH, salinity, and MPs aging were estimated. The results indicated PP MPs could adsorb amount of VEN within 24 h. The pseudo second-order kinetic model (R2 = 0.97) and Dubinin-Radushkevich model (R2 = 0.89) fitted well with the adsorption capacity of PP MPs for VEN, implying that chemical adsorption accompanied by electrostatic interaction might be the predominant mode for the interactions between PP MPs and VEN. Meanwhile, the adsorption capacity of PP MPs declined from pH of 2.5-4.5 and then increased from 4.5 to 9.5. The increased salinity (5-35 ppt) significantly suppressed the adsorption capacity. Aging by sunlight and UV triggered the formation of new functional group (carbonyl) on MPs, and then enhanced the adsorption capacity for VEN. Gaussian Model analysis further evidenced the electrostatic adsorption occurring in PP MPs and VEN. The combined exposure to PP MPs and VEN showed significantly antagonistic toxicity on Daphnia magna. The adsorption of VEN by PP MPs mitigated the lethal effects and behavioral function impairment posed by VEN on animals, implying the potential protective effects on zooplankton by PP MPs. This study for the first time provides perspective for assessing the environmental fate of MPs and antidepressants in aquatic system.
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Plásticos , Poluentes Químicos da Água , Animais , Cloridrato de Venlafaxina , Adsorção , Microplásticos , Polipropilenos , Antidepressivos , Poluentes Químicos da Água/toxicidadeRESUMO
Analyzing and characterizing the differences between networks is a fundamental and challenging problem in network science. Most previous network comparison methods that rely on topological properties have been restricted to measuring differences between two undirected networks. However, many networks, such as biological networks, social networks, and transportation networks, exhibit inherent directionality and higher-order attributes that should not be ignored when comparing networks. Therefore, we propose a motif-based directed network comparison method that captures local, global, and higher-order differences between two directed networks. Specifically, we first construct a motif distribution vector for each node, which captures the information of a node's involvement in different directed motifs. Then, the dissimilarity between two directed networks is defined on the basis of a matrix, which is composed of the motif distribution vector of every node and the Jensen-Shannon divergence. The performance of our method is evaluated via the comparison of six real directed networks with their null models, as well as their perturbed networks based on edge perturbation. Our method is superior to the state-of-the-art baselines and is robust with different parameter settings.
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A series of novel chitosan-based magnetic flocculants FS@CTS-P(AM-DMC) was prepared by molecular structure control. The characterization results showed that FS@CTS-P(AM-DMC) had a uniform size of about 21.46 nm, featuring a typical core-shell structure, and the average coating layer thickness of CTS-P(AM-DMC) was about 5.03 nm. FS@CTS-P(AM-DMC) exhibited excellent flocculation performance for kaolin suspension, achieved 92.54% turbidity removal efficiency under dosage of 150 mg/L, pH 7.0, even at high turbidity (2000 NTU) with a removal efficiency of 96.96%. The flocculation mechanism was revealed to be dominated by charge neutralization under acidic and neutral conditions, while adsorption and bridging effects play an important role in alkaline environments. The properties of magnetic aggregates during flocculation, breakage, and regeneration were studied at different pH levels and dosages. In the process of magnetophoretic, magnetic particles collide and adsorb with kaolin particles continuously due to magnetic and electrostatic attraction, transform into magnetic chain clusters, and then further form three-dimensional network magnetic aggregates that can capture free kaolin particles and other chain clusters. Particle image velocimetry confirmed the formation of eddy current of magnetic flocs and experienced three stages: acceleration, stabilization, and deceleration.
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Quitosana , Purificação da Água , Quitosana/química , Caulim/química , Floculação , Fenômenos Magnéticos , Purificação da Água/métodosRESUMO
This paper aims to study the therapeutic effect of Massa Medicata Fermentata on hyperlipidemia model rats and investigate its mechanism of hypolipidemic effect with the help of non-targeted metabolomics. The mixed hyperlipidemia model rats were constructed by giving high-fat chow. After successful modeling, the rats were divided into the model group, pravastatin sodium group(4.4 mg·kg~(-1)), lipotropic group(0.1 g·kg~(-1)), high-dose group(2.4 g·kg~(-1)), medium-dose group(1.2 g·kg~(-1)), and low-dose group(0.6 g·kg~(-1)) of Massa Medicata Fermentata, and they were administered for four weeks once daily. An equal volume of ultrapure water was given to the blank group and model group. Serum lipid level and liver hematoxylin-eosin(HE) staining were used as indicators to estimate the intervention effect of Massa Medicata Fermentata on mixed hyperlipidemia, and the changes in metabolites in plasma of mixed hyperlipidemia model rats were analyzed by non-targeted metabolomics. The mechanism of the hypolipidemic effect of Massa Medicata Fermentata was analyzed through metabolite pathway enrichment. The results showed that compared with the model group, the Massa Medicata Fermentata administration group, especially the high-dose group, could significantly reduce the content of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.05 or P<0.01), and liver HE staining revealed that the number of adipocytes in the high-dose group was reduced to some extent. The potential biomarkers obtained by non-targeted metabolomics screening included glycerol 3-phosphate, sphingomyelin, sphingosine 1-phosphate, and deoxyuridine, which were mainly involved in the sphingolipid metabolism process, glycerophospholipid metabolism process, glycerol ester metabolism pathway, and pyrimidine metabolism pathway, totaling four possible metabolic pathways related to lipid metabolism. This study provides a reference for an in-depth investigation of the hypolipidemic mechanism of Massa Medicata Fermentata, which is of great significance for further promoting the clinical application of Massa Medicata Fermentata and increasing the indications.
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Medicamentos de Ervas Chinesas , Hiperlipidemias , Ratos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Fígado , Hiperlipidemias/tratamento farmacológico , Metabolômica , Colesterol , Dieta Hiperlipídica/efeitos adversosRESUMO
Metabolism and metabolic processes have long been considered to shape the tumour immunosuppressive microenvironment. Recent research has demonstrated that T regulatory cells (Tregs) display high rates of fatty acid oxidation (FAO) and a relatively low rate of glycolysis. Sphingosine 1-phosphate (S1P), which is a G protein signalling activator involved in immune regulation and FAO modulation, has been implicated in Treg differentiation. However, the precise relation between Treg differentiation and S1P remains unclear. In this study, we isolated naïve CD4+ T cells from the spleens of 6-8-week-old BALB/c mice using magnetic bead sorting, which was used in our study for Treg differentiation. S1P stimulation was performed during Treg differentiation. We examined the oxygen consumption and palmitic acid metabolism of the differentiated Tregs and evaluated the expression levels of various proteins, including Nrf2, CPT1A, Glut1, ACC1 and PPARα, through Western blotting. Our results demonstrate that S1P promotes Treg differentiation and enhances FAO, and that the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and peroxisome proliferator-activated receptor α (PPARα) is upregulated. Furthermore, Nrf2 or PPARα knockdown dampened the Treg differentiation and FAO that were promoted by S1P, confirming that S1P can bind with S1PR4 to promote Treg differentiation through the Nrf2/PPARα signalling pathway, which may be related to FAO facilitation.
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Diferenciação Celular , Lisofosfolipídeos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2 , Oxirredução , PPAR alfa , Esfingosina , Linfócitos T Reguladores , Animais , Lisofosfolipídeos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Diferenciação Celular/imunologia , Camundongos , PPAR alfa/metabolismo , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Transdução de Sinais , Receptores de Lisoesfingolipídeo/metabolismo , Receptores de Lisoesfingolipídeo/genética , Receptores de Esfingosina-1-Fosfato/metabolismo , Ácidos Graxos/metabolismo , Células CultivadasRESUMO
Antioxidants from natural sources have long been of interest to researchers. In this paper, taking the traditional Tibetan medicine Ribes himalense as an example, an integrated approach was used to identify and isolate its chemical composition with free-radical-scavenging properties from its ethanol extract. First, the ethanol extract of Ribes himalense was pretreated using polyamide medium-pressure liquid chromatography (polyamide-MPLC), and the target fraction (Fr4) was obtained. Then, a combined HPLC mode was utilized to purify antioxidants in Fr4 under the guidance of an online HPLC-1,1-diphenyl-2-picrylhydrazyl (HPLC-DPPH) activity screening system. Finally, three antioxidants (3-caffeoylquinic acid methyl ester, rutin, and myricetin-3'-α-L-rhamnopyranoside) were isolated, and this is the first report of their presence in R. himalense. Further molecular docking studies showed that the antioxidants exhibited good binding with HO-1, Nrf2, and iNOS. In conclusion, this comprehensive approach is capable of extracting high-purity antioxidants from trace fractions of Ribes himalense and holds promise for future applications in the exploration of the chemical compositions and bioactivity of natural products.
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Antioxidantes , Ribes , Antioxidantes/farmacologia , Simulação de Acoplamento Molecular , Nylons , Cromatografia Líquida , Etanol , Extratos Vegetais/farmacologiaRESUMO
Agarwood is a resinous heartwood of Aquilaria sinensis that is formed in response to mechanical wounding. In the present study pre-treatment of Aquilaria sinensis was carried out, and then the dominant fungi were isolated and purified from the surface and electroshock holes of trees. The isolated Trichoderma sp. and Neurospora sp. were then screened for resistance against benzyl acetone and then inoculated into healthy Aquilaria sinensis trees. After six months, the agarwood was collected for analysis. The chemical composition of incense was analyzed using gas chromatography-mass spectroscopy, and 82 chemical constituents were identified. Agarwood products formed by using Trichoderma sp. and Neurospora sp. consisted of 50.22% and 48.71% ether extracts, respectively, which surpassed the 10% threshold specified by the Chinese Pharmacopoeia. Similarly, relative aromatic contents in the two agarwood products were 30.1% and 32.86%, while proportions of sesquiterpene constituents were 10.21% and 11.19%, respectively. These two agarwood-specific chemical constituents accounted for a large proportion of the total chemical composition, which showed that the generated agarwood was of good quality. The results of the study revealed that both Trichoderma sp. and Neurospora sp. were able to effectively induce agarwood production in Aquilaria sinensis trees in 6 months. This study expands the library of fungi that promote the production of agarwood from Aquilaria sinensis trees.
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Thymelaeaceae , Trichoderma , Madeira , Thymelaeaceae/microbiologia , Thymelaeaceae/química , Trichoderma/metabolismo , Trichoderma/isolamento & purificação , Madeira/microbiologia , Madeira/química , Cromatografia Gasosa-Espectrometria de Massas , Árvores/microbiologiaRESUMO
Ocean acidification causes severe shell dissolution and threats the survival of marine molluscs. The periostracum in molluscs consists of macromolecules such as proteins and polysaccharides, and protects the inner shell layers from dissolution and microbial erosion. Moreover, it serves as the primary template for shell deposition. However, the chemical composition and formation mechanism of the periostracum is largely unknown. In this study, we applied transcriptomic, proteomics, physical, and chemical analysis to unravel the mysteries of the periostracum formation in the green mussel Perna viridis Linnaeus. FTIR analysis showed that the periostracum layer was an organic membrane mainly composed of polysaccharides, lipids, and proteins, similar to that of the shell matrix. Interestingly, the proteomic study identified components enriched in tyrosine and some enzymes that evolved in tyrosine oxidation, indicating that tyrosine oxidation might play an essential role in the periostracum formation. Moreover, comparative transcriptomics suggested that tyrosine-rich proteins were intensively synthesized in the periostracum groove. After being secreted, the periostracum proteins were gradually tanned by oxidation in the seawater, and the level of crosslink increased significantly as revealed by the ATR-FTIR. Our present study sheds light on the chemical composition and putative tanning mechanism of the periostracum layer in bivalve molluscs. SIGNIFICANCE: The periostracum layer, plays an essential role in the initiation of shell biomineralization, the protection of minerals from dissolution for molluscs and especially ocean acidification conditions in the changing global climate. However, the molecular mechanism underlying the periostracum formation is not fully understood. In this study, we revealed that the oxidation and cross-link of tyrosine-rich proteins by tyrosinase are involved in periostracum formation in the green mussel Perna viridis. This study provides some insights into the first step of mussel shell formation and the robust adaptation of P. viridis to diverse habitats. These findings also help to reveal the potential acclimation of bivalves to the projected acidifying seawater.
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Perna (Organismo) , Animais , Perna (Organismo)/metabolismo , Tirosina , Água do Mar , Proteômica , Concentração de Íons de Hidrogênio , Polissacarídeos/metabolismoRESUMO
Crustaceans are the champions of mineral mobilization and deposition in the animal kingdom due to their unique ability to rapidly and periodically mineralize and demineralize their exoskeletons. They are commonly covered with mineralized exoskeletons for protection and regularly molt throughout their lives. Mineralized crustacean exoskeletons are formed under the control of macromolecules especially matrix proteins but the types of matrix proteins are understudied compared to those in molluscan shells. This gap hinders our understanding of their evolutionary paths compared with those of molluscs. Here, we comprehensively analyzed matrix proteins in the exoskeleton of two crabs, one shrimp, and one crayfish and resulted in a major improvement (â¼10-fold) in the identification of biomineralization proteins compared to conventional methods for decapod crustaceans. By a comparison with well-studied molluscan biomineralization proteins, we found that decapod crustaceans evolved novel proteins to form mineralized exoskeletons while sharing some proteins with those of molluscs. Our study sheds light on their evolution and adaption to different environment for exoskeleton formation and provides a foundation for further studies of mineralization in crustaceans under normal and climate-changed conditions. SIGNIFICANCE: Most crustaceans have mineralized exoskeletons as protection. How they form these hierarchical structures is still unclear. This is due partially to the understudied matrix proteins in the minerals. This study filled such a gap by using proteomic analysis of matrix proteins from four decapod crustacean exoskeletons. Many novel proteins were discovered which enabled a solid comparison with those of molluscs. By comparison, we proposed that crustaceans evolved novel proteins to form mineralized exoskeletons while sharing some proteins with those of molluscs. This is useful for us to understand the evolution of two major biomineralized phylum.
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Biomineralização , Decápodes , Animais , Proteômica , Minerais , MoluscosRESUMO
Myoepithelioma-like tumors of the vulvar region (MELTVR) are solid tumors found in the vulva of adult women. They have a similar histopathology to myoepithelioma but differ in immunohistochemical phenotype and genetic changes. In this study, we report four examples of MELTVR, occurred in the external genitalia and mons pubis of adult women aged 32 to 39 years. The tumors presented as subcutaneous masses without obvious tenderness. The tumors were composed of a mixture of myxoid and nonmyxoid components, and myxoid areas accounted for 5% to 80% of the tumor volume. The tumor cells were spindle-shaped or epithelioid, with abundant cytoplasm, vesicular nuclei, and small nucleoli. The nuclear atypia was mild to moderate, with 0 to 10 mitotic figures per 10 high-power fields. Immunohistochemically, all four tumors showed consistent positivity for EMA, calponin and ER; three tumors exhibited PR expression. All tumors were negative for S100 protein and SMA. AE1/AE3 expression was absent in all except one tumor, which showed rare positivity. SMARCB1/INI1 expression was deficient in all tumors. EWSR1 and FUS rearrangements were absent. All tumors were treated through surgery. All patients were alive without recurrence on most recent follow-up. Together, this overview of four additional tumors of MELTVR offers further insight into this rare and poorly understood disease.
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Most molluscs have mineralized shells to protect themselves. Although the remarkable mechanical properties of shells have been well-studied, the origin of shells is still elusive. Chitons are unique in molluscs because they are shelly Aculifera which diverged from Conchifera (comprising all the shell-bearing classes of molluscs) in the early pre-Cambrian. We developed a method to extract shell proteins from chiton shell plates (removing embedded soft tissues) and then compared the shell proteome to that of Conchifera groups. Sixteen shell matrix proteins from Acanthopleura loochooana were identified by proteomics, in which Nacrein-like, Pif-like proteins, and protocadherin were found. Additional evidences from shell proteome in another species Chiton densiliratus and comparative sequence alignment in five chitons supported a conserved biomineralization toolkit in chitons. Our findings shed light on the evolution of mineralization in chitons and pose a hypothesis that ancestral molluscs have already evolved biomineralization toolkits, which may facilitate the formation of mineralized shells.
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Poliplacóforos , Animais , Proteoma , Proteômica , Moluscos , Biomineralização , ExoesqueletoRESUMO
As dynamic graphs have become indispensable in numerous fields due to their capacity to represent evolving relationships over time, there has been a concomitant increase in the development of Temporal Graph Neural Networks (TGNNs). When training TGNNs for dynamic graph link prediction, the commonly used negative sampling method often produces starkly contrasting samples, which can lead the model to overfit these pronounced differences and compromise its ability to generalize effectively to new data. To address this challenge, we introduce an innovative negative sampling approach named Enhanced Negative Sampling (ENS). This strategy takes into account two pervasive traits observed in dynamic graphs: (1) Historical dependence, indicating that nodes frequently reestablish connections they held in the past, and (2) Temporal proximity preference, which posits that nodes are more inclined to connect with those they have recently interacted with. Specifically, our technique employs a designed scheduling function to strategically control the progression of difficulty of the negative samples throughout the training. This ensures that the training progresses in a balanced manner, becoming incrementally challenging, and thereby enhancing TGNNs' proficiency in predicting links within dynamic graphs. In our empirical evaluation across multiple datasets, we discerned that our ENS, when integrated as a modular component, notably augments the performance of four SOTA baselines. Additionally, we further investigated the applicability of ENS in handling dynamic graphs of varied attributes. Our code is available at https://github.com/qqaazxddrr/ENS.
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Redes Neurais de ComputaçãoRESUMO
The hard shells of mollusks are products of biomineralization, a distinctive feature of the Cambrian explosion. Despite our understanding of shell structure and mechanical properties, their origin remains mysterious. In addition to their shell plates, most chitons have calcium deposits on their girdles. However, the similarity of these two mineralized structures still needs to be determined, limiting our comprehension of their origins. In our study, we analyzed the matrix proteins in the spicules of chiton (Acanthopleura loochooana) and compared them with the matrix proteins in the shells of the same species. Proteomics identified 96 unique matrix proteins in spicules. Comparison of biomineralization-related matrix proteins in shell plates and spicules revealed shared proteins, including carbonic anhydrases, tyrosinase-hemocyanin, von Willebrand factor type A, cadherin, and glycine-rich unknown proteins. Based on similarities in key matrix proteins, we propose that spicules and shell plates originated from a common mineralization system in their ancestral lineage, suggesting the existence of a common core or toolkit of matrix proteins among calcifying organisms. SIGNIFICANCE: In this study, we try to understand the types and diversity of matrix proteins in the biomineralization of chiton shell plates and spicules. Through a comparative analysis, we seek insights into the core biomineralization toolkit of ancestral mollusks. To achieve this, we conducted LC-MS/MS and RT-qPCR analyses to identify the types and relative expression levels of matrix proteins in both shell plates and spicules. The analysis revealed 96 matrix proteins in the spicules. A comparison of biomineralization-related matrix proteins in shell plates and spicules from the same species revealed shared proteins including many unknown proteins unique to chitons. Blast searching reveals a universal conservation of these proteins among other chitons. Hence, we propose that spicules and shell plates originated from a common mineralization system in their ancestral lineage. Our work provides a molecular basis for studying biomineralization in polyplacophoran mollusks and understanding biomineralization evolution. In addition, it identifies potential matrix proteins that could be applied to control crystal growth.
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Biomineralização , Poliplacóforos , Animais , Cromatografia Líquida , Espectrometria de Massas em Tandem , Proteínas/análiseRESUMO
Patient readmission for ischemic stroke significantly strains the healthcare and medical insurance systems. Current understanding of the risk factors associated with these readmissions, as well as their subsequent impact on mortality within China, remains insufficient. This is particularly evident in the context of comprehensive, contemporary population studies. This 4-year retrospective cohort study included 125 397 hospital admissions for ischemic stroke from 838 hospitals located in 22 regions (13 urban and 9 rural) of a major city in western China, between January 1, 2015 and December 31, 2018. The Chi-square tests were used in univariate analysis. Accounting for intra-subject correlations of patients' readmissions, accelerated failure time (AFT) shared frailty models were used to examine readmission events and pure AFT models for mortality. Risk factors for patient readmission after ischemic stroke include frequent admission history, male gender, employee's insurance, advanced age, residence in urban areas, index hospitalization in low-level hospitals, extended length of stay (LOS) during index hospitalization, specific comorbidities and subtypes of ischemic stroke. Furthermore, our findings indicated that an additional admission for ischemic stroke increased patient mortality by 16.4% (P < .001). Stroke readmission contributed to an increased risk of hospital mortality. Policymakers can establish more effective and targeted policies to reduce readmissions for stroke by controlling these risk factors.
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AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Readmissão do Paciente , AVC Isquêmico/complicações , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Fatores de Risco , Tempo de InternaçãoRESUMO
We present a palladium-catalyzed ring-opening reaction that induces indoles to cross-couple with gem-difluorocyclopropanes. The reaction proceeds through a domino process of C-C bond activation and C-F bond elimination, followed by C-C(sp2) coupling to produce various 2-fluoroallylindoles. This method is characterized by its high functional group tolerance, good yields and high regioselectivity, under base-free conditions. The synthetic utility of the products is illustrated by the functionalization of the NH and C2 positions of the indole scaffold.