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Non-alcoholic fatty liver disease (NAFLD) not only could cause abnormal lipid metabolism in the liver, but also could cause liver inflammation. Previous studies have shown that Polysaccharide of Atractylodes macrocephala Koidz (PAMK) could alleviate animal liver inflammatory damage and alleviate NAFLD in mice caused by high-fat diet(HFD), but regulation of liver inflammation caused by NAFLD has rarely been reported. In this study, an animal model of non-alcoholic fatty liver inflammation in the liver of mice was established to explore the protective effect of PAMK on the liver of mice. The results showed that PAMK could alleviate the abnormal increase of body weight and liver weight of mice caused by HFD, alleviate the abnormal liver structure of mice, reduce the level of oxidative stress and cytokine secretion in the liver of mice, and downregulate the mRNA expression of TLR4, MyD88, NF-κB and protein expression of P-IκB, P-NF-κB-P65, TLR4, MyD88, NF-κB in the liver. These results indicate that PAMK could alleviate hepatocyte fatty degeneration and damage, oxidative stress and inflammatory response of the liver caused by NAFLD in mice.
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Acute ischemic stroke (AIS) is one of the most predominant causes of mortality and disability in China. Significant uncertainties in stroke diagnosis and time of onset have resulted in inconsistent evidence on the association between ambient air pollution and the risk of AIS. The present study aimed to evaluate the impact of air pollution on AIS onset based on high time-resolution air pollution data and a stroke-specific registry across the past five years. Hourly concentrations of PM2.5, PM10, O3, SO2, CO, NO2 and nitrous acid (HONO) were monitored from 2017 to 2021, with which a distributed lag non-linear model and conditional logistic regression models coupled with a time-stratified case-crossover design were applied to 106,623 AIS cases recorded in the Shanghai Stroke Service (4S) database during the study period. Results from the conditional logistic regression models indicate that acute exposure to PM2.5, PM10, SO2, NO2 and HONO was found to be associated with AIS onset, respectively. The corresponding cumulative excessive risks of AIS onset were 0.8 %, 1 %, 2.4 %, 2.1 % and 1.8 % for each interquartile range increase in the respective concentration. The longest lag-effect (up to 13 h) was observed for reactive nitrogen species (RNS), such as NO2 and HONO, which remained robust in two-pollutant models. Similar important role of RNS in AIS onset were confirmed by the distributed lag non-linear model. By demonstrating the transient effect of ambient air pollution on AIS, especially the relationships between RNS and AIS for the first time, our study provides stringent evidence for future mitigation strategies for pollution emission and public health.
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Poluentes Atmosféricos , Poluição do Ar , AVC Isquêmico , Espécies Reativas de Nitrogênio , China/epidemiologia , Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Humanos , AVC Isquêmico/epidemiologia , Material Particulado/análise , Exposição Ambiental/estatística & dados numéricos , Masculino , Feminino , IdosoRESUMO
Senecavirus A (SVA) is a causative agent that can cause vesicular disease in swine, which causes a great threat to the swine husbandry in the world. Therefore, it is necessary to develop a vaccine that can effectively prevent the spread of SVA. In this study, we developed a 24-polymeric nano-scaffold using ß-annulus peptide from tomato bushy effect virus (TBSV) by coupling this antigen to SVA B cell epitope VP121-26 and VP2 proteins via linkers, respectively. The SVA-based nanoparticle protein of the VP1(B)-ß-VP2 was expressed and purified by low-cost prokaryotic system to prepare a SVA nanoparticle vaccine. The immunological protective effect of SVA nanoparticle vaccine was evaluated in mouse and swine models, respectively. The results suggested that both mice and swine could induce high levels SVA neutralizing antibodies and IgG antibodies after two doses immunization. In addition, the swine challenge protection experiment showed that the protection rate of immune SVA nanoparticle vaccine and SVA inactivated vaccine both were 80â¯%, while the negative control had no protection effect. It demonstrated that SVA nanoparticle vaccine effectively prevented SVA infection in swine. In summary, the preparation of SVA vaccine by using ß-annulus peptide is a promising candidate vaccine for prevent SVA transmission, and provides a new idea for the development of novel SVA vaccines.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Nanovacinas , Infecções por Picornaviridae , Picornaviridae , Doenças dos Suínos , Vacinas Virais , Animais , Feminino , Camundongos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Proteínas do Capsídeo/imunologia , Camundongos Endogâmicos BALB C , Nanovacinas/administração & dosagem , Nanovacinas/imunologia , Picornaviridae/imunologia , Infecções por Picornaviridae/veterinária , Infecções por Picornaviridae/prevenção & controle , Infecções por Picornaviridae/imunologia , Infecções por Picornaviridae/virologia , Suínos , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/virologia , Doenças dos Suínos/imunologia , Proteínas Estruturais Virais/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagemRESUMO
Transmetalation represents an appealing strategy toward fabricating and tuning functional metal-organic polymers and frameworks for diverse applications. In particular, building two-dimensional metal-organic and organometallic networks affords versatile nanoarchitectures of potential interest for nanodevices and quantum technology. The controlled replacement of embedded metal centers holds promise for exploring versatile material varieties by serial modification and different functionalization. Herein, we introduce a protocol for the modification of a single-layer carbon-metal-based organometallic network via transmetalation. By integrating external Cu atoms into the alkynyl-Ag organometallic network constructed with 1,3,5-triethynylbenzene precursors, we successfully realized in situ its highly regular alkynyl-Cu counterpart on the Ag(111) surface. While maintaining a similar lattice periodicity and pore morphology to the original alkynyl-Ag sheet, the Cu-based network exhibits increased thermal stability, guaranteeing improved robustness for practical implementation.
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Preservation of mitochondrial functionality is essential for heart hemostasis and cardiovascular diseases treatment. However, the current nanomedicines including liposomes, polymers and inorganic nanomaterials are severely hindered by poor stability, high manufacturing costs and potential biotoxicity. In this research, we present novel polyphenolic nanoparticles (NPs) derived from naturally occurring pomegranate peel (PP, labelled as PPP NPs), which exhibit potent antioxidative and anti-inflammatory properties, serving as a modulator of mitochondrial function. PPP NPs have been identified to improve survival rates in models of mitochondrial depletion through enhancement of cardiomyocyte proliferation and the reduction of DNA damage. Moreover, PPP NPs can effectively inhibit the production of reactive oxygen species and inflammatory mediators in lipopolysaccharide (LPS)-induced mitochondrial damage. Utilizing human engineered heart tissue and mice models, PPP NPs were found to significantly improve contractile function and alleviate inflammation activities after LPS treatment. Mechanically, PPP NPs regulated inflammatory responses via a m6A dependent manner, as determined using RNA-seq and MeRIP-seq analyses. Collectively, these insights underscore the potential of PPP NPs as a novel therapeutic approach for mitochondrial dysfunction.
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Drought significantly impacts cotton square (flower buds with bracts) shedding, directly affecting yield. To address the internal physiological mechanisms of drought affecting cotton square shedding, a polyethylene glycol-simulated drought study was conducted with Dexiamian 1 and Yuzaomian 9110 to investigate cell wall degradation changes in the base of pedicel where the detachment of cotton square takes place, and its relationship with cotton square shedding. Results revealed significant decreases in cellulose, hemicellulose, and pectin contents in the base of square pedicel, leading to cell wall degradation and consequent square shedding. Furthermore, drought stress exacerbated the hydrolysis of cellulose and pectin in the base of pedicel, although not hemicellulose, resulting in more noticeable alterations in the morphology and structure of the base of pedicel, such as more significant degradation in the epidermis, cortex, and phloem. Regarding the cellulose hydrolysis, drought mainly increased the expression of genes ß-glucosidase (GhBG1) and endoglucanase (GhEG1), and the activity of ß-glucosidase and endoglucanase in the base of pedicel, promoting the conversion of cellulose to cellobiose, and eventually glucose. Regarding the pectin hydrolysis, drought significantly enhanced the expression of the gene pectin methylase (GhPE1), thereby accelerating pectin hydrolysis to generate polygalacturonic acid. Additionally, drought increased the expression of genes pectin lyase (GhPL1) and polygalacturonase (GhPG1), as well as the activity of pectin lyase, which further accelerated the hydrolysis of polygalacturonic acid into galacturonic acid. These findings suggest that drought mainly promotes cellulose and pectin hydrolysis in the base of pedicel, hastening cell wall degradation and final cotton square shedding.
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Parede Celular , Secas , Gossypium , Pectinas , Parede Celular/metabolismo , Gossypium/metabolismo , Gossypium/genética , Pectinas/metabolismo , Celulose/metabolismo , Flores/metabolismo , Hidrólise , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Polissacarídeos/metabolismoRESUMO
Induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) therapy has emerged as a highly promising field of heart repair. Lin et al.1 presented compelling evidence on the long-term engraftment and maturation of autologous iPSC-CMs in two rhesus macaques, demonstrating unprecedented cardiac autografting data in large animal models without the need of immunosuppressants.
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Células-Tronco Pluripotentes Induzidas , Macaca mulatta , Miócitos Cardíacos , Animais , Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/citologia , Autoenxertos , Humanos , Sobrevivência Celular , Diferenciação CelularRESUMO
Here, we present a protocol for the quantitative assessment of rat and mouse cardiomyocyte proliferation both in vitro and in vivo. For the in vivo approach, we describe steps for the isolation of neonatal rat cardiomyocytes and the employment of various indicators to quantify cell proliferation. We then detail in vivo procedures that incorporate comprehensive assays and a genetic lineage tracing strategy to evaluate endogenous cardiomyocyte proliferation. This protocol can be modified to investigate other mammalian cardiomyocyte proliferation. For complete details on the use and execution of this protocol, please refer to Ji et al.1.
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Ulcerative colitis (UC) manifests clinically with chronic intestinal inflammation and microflora dysbiosis. Although biologics can effectively control inflammation, efficient delivery to the colon and colon epithelial cells remains challenging. Milk-derived extracellular vesicles (EV) show promise as an oral delivery tool, however, the ability to load biologics into EV presents challenges to therapeutic applications. Here, we demonstrate that fusing cell-penetrating peptide (TAT) to green fluorescent protein (GFP) enabled biologics loading into EV and protected against degradation in the gastrointestinal environment in vitro and in vivo after oral delivery. Oral administration of EV loaded with anti-tumour necrosis factor-α (TNF-α) nanobody (VHHm3F) (EVVHH) via TAT significantly reduced tissue TNF-α levels and alleviated pathologies in mice with acute UC, compared to VHH alone. In mice with chronic UC, simultaneously introducing VHH and an antimicrobial peptide LL37 into EV (EVLV), then administering orally improved intestinal barrier, inflammation and microbiota balance, resulted in relief of UC-induced depression and anxiety. Collectively, we demonstrated that oral delivery of EVLV effectively alleviated UC in mice and TAT efficiently loaded biologics into EV to confer protection from degradation in the gastrointestinal tract. This therapeutic strategy is promising for UC and is a simple and generalizable approach towards drug-loaded orally-administrable EV treatment for other diseases.
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Colite Ulcerativa , Vesículas Extracelulares , Leite , Anticorpos de Domínio Único , Fator de Necrose Tumoral alfa , Animais , Colite Ulcerativa/tratamento farmacológico , Vesículas Extracelulares/metabolismo , Camundongos , Fator de Necrose Tumoral alfa/metabolismo , Anticorpos de Domínio Único/farmacologia , Anticorpos de Domínio Único/uso terapêutico , Peptídeos Antimicrobianos/farmacologia , Catelicidinas , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Peptídeos Penetradores de Células/farmacologia , Humanos , Administração Oral , Masculino , FemininoRESUMO
Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.
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Movimento Celular , Fibrose , Rim , Linfócitos , Receptor de Morte Celular Programada 1 , Receptores CXCR6 , Receptores de Interleucina , Transdução de Sinais , Animais , Fibrose/imunologia , Camundongos , Receptores CXCR6/metabolismo , Receptores CXCR6/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais/imunologia , Movimento Celular/imunologia , Humanos , Rim/patologia , Rim/imunologia , Rim/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Receptores de Interleucina/metabolismo , Receptores de Interleucina/imunologia , Camundongos Endogâmicos C57BL , Nefropatias/imunologia , Nefropatias/metabolismo , Nefropatias/patologia , Imunidade Inata/imunologia , Camundongos Knockout , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestinos/imunologia , Intestinos/patologiaRESUMO
Colorectal cancer (CRC) has a high degree of heterogeneity and identifying the genetic information of individual tumor cells could help enhance our understanding of tumor biology and uncover potential therapeutic targets for CRC. In this study, we identified LPCAT2+ tumor cell populations with less malignancy than LPCAT2- tumor cells in human and mouse CRC tissues using scRNA-seq. Combining in vitro and in vivo experiments, we found that LPCAT2 could inhibit the proliferation of CRC cells by inducing ferroptosis. Mechanistically, LPCAT2 arrested PRMT1 in cytoplasm of CRC cells via regulating acetylation of PRMT1 at the K145 site. In turn, PRMT1 enhanced SLC7A11 promoter activity. Thus, LPCAT2 attenuated the positive regulatory effect of PRMT1 on SLC7A11 promoter. Notably, SLC7A11 acts as a ferroptosis regulator. Furthermore, in LPCAT2 knockout mice (LPCAT2-/-) colon cancer model, we found that LPCAT2-/- mice exhibited more severe lesions, while PRMT1 or SLC7A11 inhibitors delayed the progression. Altogether, we elucidated that LPCAT2 suppresses SLC7A11 expression by inhibiting PRMT1 nuclear translocation, thereby inducing ferroptosis in CRC cells. Moreover, inhibitors of the PRMT1/SLC7A11 axis could delay tumor progression in CRC with low LPCAT2 expression, making it a potentially effective treatment for CRC.
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Sistema y+ de Transporte de Aminoácidos , Neoplasias Colorretais , Progressão da Doença , Proteína-Arginina N-Metiltransferases , Animais , Humanos , Camundongos , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Ferroptose/genética , Ferroptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Camundongos Knockout , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismoRESUMO
Areas of interest (AOIs) are well-established means of providing semantic information for visualizing, analyzing, and classifying gaze data. However, the usual manual annotation of AOIs is time-consuming and further impaired by ambiguities in label assignments. To address these issues, we present an interactive labeling approach that combines visualization, machine learning, and user-centered explainable annotation. Our system provides uncertainty-aware visualization to build trust in classification with an increasing number of annotated examples. It combines specifically designed EyeFlower glyphs, dimensionality reduction, and selection and exploration techniques in an integrated workflow. The approach is versatile and hardware-agnostic, supporting video stimuli from stationary and unconstrained mobile eye tracking alike. We conducted an expert review to assess labeling strategies and trust building.
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Multienzyme assemblies mediated by multivalent interaction play a crucial role in cellular processes. However, the three-dimensional (3D) programming of an enzyme complex with defined enzyme activity in vitro remains unexplored, primarily owing to limitations in precisely controlling the spatial topological configuration. Herein, we introduce a nanoscale 3D enzyme assembly using a tetrahedral DNA framework (TDF), enabling the replication of spatial topological configuration and maintenance of an identical edge-to-edge distance akin to natural enzymes. Our results demonstrate that 3D nanoscale enzyme assemblies in both two-enzyme systems (glucose oxidase (GOx)/horseradish peroxidase (HRP)) and three-enzyme systems (amylglucosidase (AGO)/GOx/HRP) lead to enhanced cascade catalytic activity compared to the low-dimensional structure, resulting in â¼5.9- and â¼7.7-fold enhancements over homogeneous diffusional mixtures of free enzymes, respectively. Furthermore, we demonstrate the enzyme assemblies for the detection of the metabolism biomarkers creatinine and creatine, achieving a low limit of detection, high sensitivity, and broad detection range.
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Enzimas Imobilizadas , Glucose Oxidase , Enzimas Imobilizadas/química , Peroxidase do Rábano Silvestre/química , Glucose Oxidase/química , DNA/químicaRESUMO
BACKGROUND: Currently, there is a lack of ideal risk prediction tools in the field of emergency general surgery (EGS). The American Association for the Surgery of Trauma recommends developing risk assessment tools specifically for EGS-related diseases. In this study, we sought to utilize machine learning (ML) algorithms to explore and develop a web-based calculator for predicting five perioperative risk events of eight common operations in EGS. METHOD: This study focused on patients with EGS and utilized electronic medical record systems to obtain data retrospectively from five centers in China. Five ML algorithms, including Random Forest (RF), Support Vector Machine, Naive Bayes, XGBoost, and Logistic Regression, were employed to construct predictive models for postoperative mortality, pneumonia, surgical site infection, thrombosis, and mechanical ventilation >48 h. The optimal models for each outcome event were determined based on metrics, including the value of the Area Under the Curve, F1 score, and sensitivity. A comparative analysis was conducted between the optimal models and Emergency Surgery Score (ESS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and American Society of Anesthesiologists (ASA) classification. A web-based calculator was developed to determine corresponding risk probabilities. RESULT: Based on 10 993 patients with EGS, we determined the optimal RF model. The RF model also exhibited strong predictive performance compared with the ESS, APACHE II score, and ASA classification. Using this optimal model, the authors developed an online calculator with a questionnaire-guided interactive interface, catering to both the preoperative and postoperative application scenarios. CONCLUSIONS: The authors successfully developed an ML-based calculator for predicting the risk of postoperative adverse events in patients with EGS. This calculator accurately predicted the occurrence risk of five outcome events, providing quantified risk probabilities for clinical diagnosis and treatment.
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Aprendizado de Máquina , Humanos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Adulto , Idoso , China/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Abdome/cirurgia , Emergências , APACHE , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Cirurgia Geral , Cirurgia de Cuidados CríticosRESUMO
BACKGROUND: Lipopolysaccharide (LPS) can induce systemic inflammation and affect the growth and development of poultry. As a kind of traditional Chinese medicine, polysaccharide of Atractylodes macrocephala Koidz (PAMK) can effectively improve the growth performance of animals and improve the immunity of animal bodies. OBJECTIVES: The purpose of this study was to investigate the effects of PAMK on LPS-induced inflammatory response, proliferation, differentiation and apoptosis of chicken embryonic myogenic cells. METHODS: We used chicken embryonic myogenic cells as a model by detecting EdU/MYHC immunofluorescence, the expression of inflammation, proliferation, differentiation-related genes and proteins and the number of apoptotic cells in the condition of adding LPS, PAMK, belnacasan (an inhibitor of Caspase1) or their combinations. RESULTS: The results showed that LPS stimulation increased the expression of inflammatory factors, inhibited proliferation and differentiation, and excessive apoptosis in chicken embryonic myogenic cells, and PAMK alleviated these adverse effects induced by LPS. After the addition of belnacasan (inhibitor of Caspase1), apoptosis in myogenic cells was inhibited, and therefore, the number of apoptotic cells and the expression of pro-apoptotic genes Caspase1 and Caspase3 were increased. In addition, belnacasan inhibited the increased expression of inflammatory factors, inhibited proliferation, differentiation and excessive apoptosis in chicken embryonic myogenic cells induced by LPS. CONCLUSIONS: This study provides a theoretical basis for further exploring the mechanism of action of PAMK and exogenous LPS on chicken embryonic myogenic cells and lays the foundation for the development and application of green feed additives in animal husbandry industry.
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Atractylodes , Lipopolissacarídeos , Animais , Lipopolissacarídeos/toxicidade , Galinhas , Polissacarídeos/farmacologia , Apoptose , Proliferação de Células , Inflamação/veterináriaRESUMO
The advances in AI-enabled techniques have accelerated the creation and automation of visualizations in the past decade. However, presenting visualizations in a descriptive and generative format remains a challenge. Moreover, current visualization embedding methods focus on standalone visualizations, neglecting the importance of contextual information for multi-view visualizations. To address this issue, we propose a new representation model, Chart2Vec, to learn a universal embedding of visualizations with context-aware information. Chart2Vec aims to support a wide range of downstream visualization tasks such as recommendation and storytelling. Our model considers both structural and semantic information of visualizations in declarative specifications. To enhance the context-aware capability, Chart2Vec employs multi-task learning on both supervised and unsupervised tasks concerning the cooccurrence of visualizations. We evaluate our method through an ablation study, a user study, and a quantitative comparison. The results verified the consistency of our embedding method with human cognition and showed its advantages over existing methods.
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Efficient biocatalytic cascade reactions play a crucial role in guiding intricate, specific and selective intracellular transformation processes. However, the catalytic activity of the enzyme cascade reaction in bulk solution was greatly impacted by the spatial morphology and inter-enzyme distance. The programmability and addressability nature of framework nucleic acid (FNA) allows to be used as scaffold for immobilization and to direct the spatial arrangement of enzyme cascade molecules. Here, we used tetrahedral DNA framework (TDF) as nanorulers to assemble two enzymes for constructing a double-enzyme complex, which significantly enhance the catalytic efficiency of sarcosine oxidase (SOx)/horseradish peroxidase (HRP) cascade system. We synthesized four types of TDF nanorulers capable of programming the lateral distance between enzymes from 5.67â nm to 12.33â nm. Enzymes were chemical modified by ssDNA while preserving most catalytic activity. Polyacrylamide gel electrophoresis (PAGE), transmission electron microscopy (TEM) and atomic force microscopy (AFM) were used to verify the formation of double-enzyme complex. Four types of double-enzyme complexes with different enzyme distance were constructed, in which TDF26(SOx+HRP) exhibited the highest relative enzyme cascade catalytic activity, ~3.11-fold of free-state enzyme. Importantly, all the double-enzyme complexes demonstrate a substantial improvement in enzyme cascade catalytic activity compared to free enzymes.
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Biocatálise , DNA , Peroxidase do Rábano Silvestre , Sarcosina Oxidase , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , DNA/química , DNA/metabolismo , Sarcosina Oxidase/química , Sarcosina Oxidase/metabolismo , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismoRESUMO
Black carbon (BC) and brown carbon (BrC) are aerosols that absorb light and thereby contribute to climate change. In this study, the light absorption properties and spatiotemporal distributions of equivalent BC (eBC) and BrC aerosols were determined based on continuous measurements of aerosol light absorption from January to August 2017, using a seven-channel aethalometer at 49 sampling sites in China. The source apportionments of BC and BrC were identified using the BC/PM2.5, absorption Ångström exponent, the concentration-weighted trajectory method, and the random forest model. Based on the results, BC was the dominant light absorber, whereas BrC was responsible for a higher proportion of the light absorption in northern compared to southern China. The light absorption of BrC was highest in winter (34.3 Mm-1), followed by spring (19.0 Mm-1) and summer (3.6 Mm-1). The combustion of liquid fuels accounted for over 50 % of the light absorption coefficient of BC in most cities and the importance of carbon monoxide (CO) and nitrogen dioxide (NO2) was over 10 % for BC emitted by liquid fuel combustion, based on the random forest model. The contribution of solid fuel combustion to BC in the north was larger than that in the southern regions as coal combustion and crop residue burning are important emission sources of BC in most northern cities. The contribution of primary BrC to light absorption was high in some northern cities, whereas that of secondary BrC was prevalent in some southern cities. The diurnal variations in secondary BrC were affected by changes in odd oxygen and relative humidity, which promoted the photobleaching of the chromophores and aqueous-phase reactions of secondary BrC.
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Utilization of lipids as energy substrates after birth causes cardiomyocyte (CM) cell-cycle arrest and loss of regenerative capacity in mammalian hearts. Beyond energy provision, proper management of lipid composition is crucial for cellular and organismal health, but its role in heart regeneration remains unclear. Here, we demonstrate widespread sphingolipid metabolism remodeling in neonatal hearts after injury and find that SphK1 and SphK2, isoenzymes producing the same sphingolipid metabolite sphingosine-1-phosphate (S1P), differently regulate cardiac regeneration. SphK2 is downregulated during heart development and determines CM proliferation via nuclear S1P-dependent modulation of histone acetylation. Reactivation of SphK2 induces adult CM cell-cycle re-entry and cytokinesis, thereby enhancing regeneration. Conversely, SphK1 is upregulated during development and promotes fibrosis through an S1P autocrine mechanism in cardiac fibroblasts. By fine-tuning the activity of each SphK isoform, we develop a therapy that simultaneously promotes myocardial repair and restricts fibrotic scarring to regenerate the infarcted adult hearts.
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Coração , Lisofosfolipídeos , Esfingolipídeos , Esfingosina/análogos & derivados , Animais , Esfingolipídeos/metabolismo , Isoenzimas , Mamíferos/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismoRESUMO
OBJECTIVE: Stocking density (SD) is an important issue in the poultry industry, which is related to the production performance, intestinal health and immune status. In the present study, the effects of SD on the metabolism and homeostasis of uric acid as well as the related functions of the liver and kidney in ducks were examined. METHODS: A total of 360 healthy 56-day-old Shan-ma ducks were randomly divided into the low stocking density (n = 60, density = 5 birds/m2), medium stocking density (n = 120, density = 10 birds/m2) and high stocking density groups (HSD; n = 180, density = 15 birds/m2). Samples were collected in the 3rd, 6th, and 9th weeks of the experiment for analysis. RESULTS: The serum levels of uric acid, lipopolysaccharide and inflammatory cytokines (interleukin-1ß [IL-1ß], IL-8, and tumor necrosis factor-α [TNF-α]) were increased significantly in the HSD group. Serious histopathological lesions could be seen in both the livers and kidneys in the HSD group in the 9th week. The mRNA expression levels of inflammatory cytokines (IL-8 and TNF-α) and related pathway components (toll-like receptor 4, myeloid differentiation primary response gene 88, and nuclear factor-κB) were increased significantly in both the livers and kidneys in the HSD group. The mRNA expression levels of enzymes (adenosine deaminase, xanthine oxidase, phosphoribosyl pyrophosphate amidotransferase, and phosphoribosyl pyrophosphate synthetase 1) related to the synthesis of uric acid increased significantly in the livers in the HSD group. However, the mRNA expression level of solute carrier family 2 member 9, which plays an important role in the excretion of uric acid by the kidney, was decreased significantly in the kidneys in the HSD group. CONCLUSION: These results indicated that a higher SD could cause tissue inflammatory lesions in the liver and kidney and subsequently affect the metabolism and homeostasis of uric acid, and is helpful for guiding decisions related to the breeding and production of ducks.