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Tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC) promote tumor cell metastasis by interacting with cancer cells. Ginsenoside Re is capable of modulating the host immune system and exerts anticancer effects through multiple pathways. Both AMPK and STING are involved in the regulation of MΦ polarization, thereby affecting tumor progression. However, whether there is a regulatory relationship between them and its effect on MΦ polarization and tumor progression is unclear. The aim of this study was to provide mechanistic evidence that ginsenoside Re modulates MΦ phenotype through inhibition of the AMPKα1/STING positive feedback loop and thus exerts an antimetastatic effect in NSCLC immunotherapy. Cell culture models and conditioned media (CM) systems were constructed, and the treated MΦ were analyzed by database analysis, RT-PCR, Western blotting, flow cytometry, and immunofluorescence to determine the regulatory relationship between AMPK and STING and the effects of ginsenoside Re on MΦ polarization and tumor cells migration. The effects of ginsenoside Re (10, 20 mg/kg/day) on TAMs phenotype as well as tumor progression in mice were assessed by HE staining, immunohistochemical staining, and Western blotting. In this study, AMPKα1/STING positive feedback loop in NSCLC TAMs induced M2 type polarization, which in turn promoted NSCLC cell migration. In addition, ginsenoside Re was discovered to inhibit M2-like MΦ polarization, thereby inhibiting NSCLC cell migration. Mechanistically, Re was able to inhibit the formation of the AMPKα1/STING positive feedback loop, thereby inhibiting its induction of M2-like MΦ and consequently inhibiting the epithelial-mesenchymal transition (EMT) process of NSCLC cells. Furthermore, in mouse models, Re was found to suppress LLC tumor growth and colonization by inhibiting M2-type polarization of TAMs. Our finding indicates that ginsenoside Re can effectively modulate MΦ polarization and thus play an important role in antimetastatic immunotherapy of NSCLC.
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The microbial synthesis of sulfonolipids within the human body is likely involved in maintaining human health or causing diseases. However, the enzymes responsible for their biosynthesis remain largely unknown. In this study, we identified and verified the role of 3-ketocapnine reductase, the third-step enzyme, in the four-step conversion of l-phosphoserine into sulfobacin B both in vivo and in vitro. This finding builds upon our previous research into sulfonolipid biosynthesis, which focused on the vaginal bacterium Chryseobacterium gleum DSM 16776 and the gut bacterium Alistipes finegoldii DSM 17242. Through comprehensive gene mapping, we demonstrate the widespread presence of potential sulfonolipid biosynthetic genes across diverse bacterial species inhabiting various regions of the human body. These findings shed light on the prevalence of sulfonolipid-like metabolites within the human microbiota, suggesting a potential role for these lipid molecules in influencing the intricate biointeractions within the complex microbial ecosystem of the human body.
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Ultrasonic flow meters are crucial measuring instruments in natural gas transportation pipeline scenarios. The collected flow velocity data, along with the operational conditions data, are vital for the analysis of the metering performance of ultrasonic flow meters and analysis of the flow process. In practical applications, high requirements are placed on the modeling accuracy of ultrasonic flow meters. In response, this paper proposes an ultrasonic flow meter modeling method based on a combination of data learning and industrial physics knowledge. This paper builds ultrasonic flow meter flow velocity prediction models under different working conditions, combining pipeline flow field velocity distribution knowledge for data preprocessing and loss function design. By making full use of the characteristics of the physics and data learning, the prediction results are close to the real acoustic path flow velocity distribution; thus, the model has high accuracy and interpretability. Experiments are conducted to prove that the prediction error of the proposed method can be controlled within 1%, which can meet the needs of ultrasonic flow meter modeling and subsequent performance analysis in actual production.
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In the background of global warming, coral bleaching induced by elevated seawater temperature is the primary cause of coral reef degradation. Coral microbiome engineering using the beneficial microorganisms for corals (BMCs) has become a hot spot in the field of coral reef conservation and restoration. Investigating the potential of alleviating thermal stress by quorum quenching (QQ) bacteria may provide more tools for coral microbial engineering remediation. In this study, QQ bacteria strain Pseudoalteromonas piscicida SCSIO 43740 was screened among 75 coral-derived bacterial strains, and its quorum sensing inhibitor (QSI) compound was isolated and identified as 2,4-di-tert-butylphenol (2,4-DTBP). Then, the thermal stress alleviating potential of QQ bacteria on coral Pocillopora damicornis was tested by a 30-day controlled experiment with three different treatments: control group (Con: 29 °C), high temperature group (HT: 31 °C), and the group of high temperature with QQ bacteria inoculation (HTQQ: 31 °C + QQ bacteria). The results showed that QQ bacteria SCSIO 43740 inoculation can significantly mitigate the loss of symbiotic algae and impairment of photosynthesis efficiency of coral P. damicornis under thermal stress. Significant difference in superoxide dismutase (SOD) and catalase (CAT) enzyme activities between HT and HTQQ was not observed. In addition, QQ bacteria inoculation suppressed the coral microbial community beta-dispersion and improved the stability of microbial co-occurrence network under thermal stress. It was suggested that QQ bacteria inoculation can alleviate coral thermal stress via reshaping microbial interaction and maintain community stability of coral microbiome. This study provided new evidence for the probiotic function of QQ bacteria in corals, which shedding light on the development of new microbiological tools for coral reef conservation.
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BACKGROUND: Vorinostat (SAHA) is a histone deacetylase inhibitor that has shown clinical efficacy against advanced cutaneous T-cell lymphoma (CTCL). However, only a subset of patients with CTCL (30-35%) respond to SAHA and the response is not always sustainable. Thus, understanding the mechanisms underlying evasive resistance in this cancer is an unmet medical need to improve the efficacy of current therapies. PURPOSE: This study aims to identify factors contributing to resistance against SAHA in CTCL and ways to mitigate it. METHODS AND RESULTS: In this study, we demonstrated that attenuated reactive oxygen species (ROS) induces the expression of interleukin (IL)-2Rα, one of the IL-2 receptors, which drives resistance to SAHA in CTCL. We also determined that cantharidin could overcome SAHA resistance to CTCL by blocking IL-2Rα-related signaling via ROS-dependent manner. Mechanistically, accelerated translation of IL-2Rα contributes to excessive IL-2Rα protein formation as a result of reduced ROS levels in SAHA-resistant CTCL. At the same time, amplified IL-2R signals are evidenced by strengthened interaction of IL-2Rß with IL-2Rγ and Janus kinase/signal transducer and activator of transcription molecules, and by increased expression of protein kinase B (AKT)/mTOR and mitogen-activated protein kinase signaling. Moreover, cantharidin, an active constituent of Mylabris used in traditional Chinese medicine, markedly increased ROS levels, and thereby restrained IL-2Rα translation, resulting in suppression of downstream pathways in SAHA-resistant cells. Cantharidin is also found to synergize with SAHA and triggers SAHA-resistant cell death via IL-2R signaling both in vitro and in vivo. CONCLUSION: Our study uncovers a novel molecular mechanism of acquired SAHA resistance and also suggests that using cantharidin is a potential approach to overcome CTCL therapy resistance. Our findings underlie the therapeutic potential of cantharidin in treating CTCL.
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Cantaridina , Resistencia a Medicamentos Antineoplásicos , Linfoma Cutâneo de Células T , Espécies Reativas de Oxigênio , Transdução de Sinais , Vorinostat , Humanos , Cantaridina/farmacologia , Cantaridina/uso terapêutico , Vorinostat/farmacologia , Vorinostat/uso terapêutico , Linfoma Cutâneo de Células T/tratamento farmacológico , Linfoma Cutâneo de Células T/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Camundongos , Linhagem Celular Tumoral , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
Predicting the timing of incoming information allows brain to optimize information processing in dynamic environments. However, the effects of temporal predictions on tactile perception are not well established. In this study, two experiments were conducted to determine how temporal predictions interact with conditional probabilities in tactile perceptual processing. In Experiment 1, we explored the range of the interval between preceding ready cues and imperative targets in which temporal prediction effects can be observed. This prediction effect was observed for intervals of 500 and 1,000â ms. In Experiment 2, we investigated the benefits of temporal predictions on tactile perception while manipulating the conditional probability (setting the stimulus onset earlier or later than the predicted moment in short and long intervals). Our results revealed that this effect became stronger as the probability of the stimulus at the predicted time point increased under short-interval conditions. Together, our results show that the difficulty of transferring processing resources increases in temporally dynamic environments, suggesting a greater subjective cost associated with maladaptive responses to temporally uncertain events.
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Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 µg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.
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Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/química , Humanos , Família Multigênica , Camundongos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/genética , Peptídeos Antimicrobianos/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana/efeitos dos fármacos , Genoma Bacteriano/genética , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Biologia Computacional/métodos , Cisteína/metabolismo , Cisteína/químicaRESUMO
Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in mice. Hepatic APOO expression was increased in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (Apoo-/-) model, it was found that APOO depletion aggravated diet-induced obesity and elevated plasma cholesterol levels. Upon crossing with low-density lipoprotein receptor (LDLR) and apolipoprotein E (APOE) knockout hyperlipidemic mouse models, Apoo-/- Apoe-/- and Apoo-/- Ldlr-/- mice exhibited elevated plasma cholesterol levels, with more severe atherosclerotic lesions than littermate controls. This indicated the effects of APOO on cholesterol metabolism independent of LDLR and APOE. Moreover, APOO deficiency reduced cholesterol excretion through bile and feces while decreasing phospholipid unsaturation by inhibiting NRF2 and CYB5R3. Restoration of CYB5R3 expression in vivo by adeno-associated virus (AAV) injection reversed the reduced degree of phospholipid unsaturation while decreasing blood cholesterol levels. This represents the first in vivo experimental validation of the role of APOO in plasma cholesterol metabolism independent of LDLR and elucidates a previously unrecognized cholesterol metabolism pathway involving NRF2/CYB5R3. APOO may be a metabolic regulator of total-body cholesterol homeostasis and a target for atherosclerosis management. Apolipoprotein O (APOO) regulates plasma cholesterol levels and atherosclerosis through a pathway involving CYB5R3 that regulates biliary and fecal cholesterol excretion, independently of the LDL receptor. In addition, down-regulation of APOO may lead to impaired mitochondrial function, which in turn aggravates diet-induced obesity and fat accumulation.
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Colesterol , Fator 2 Relacionado a NF-E2 , Receptores de LDL , Animais , Receptores de LDL/metabolismo , Colesterol/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos , Camundongos Knockout , Camundongos Endogâmicos C57BL , Metabolismo dos Lipídeos , Masculino , Aterosclerose/metabolismo , Apolipoproteínas/metabolismo , Apolipoproteínas/genética , Humanos , Fígado/metabolismo , Apolipoproteínas E/metabolismo , Hiperlipidemias/metabolismoRESUMO
Purpose: The aim of this study was to elucidate the role of Sema4D in the pathogenesis of senescence-associated choroidal neovascularization (CNV) and to explore its underlying mechanisms. Methods: In this study, we utilized a model of laser-induced CNV in both young (3 months old) and old (18 months old) mice, including those with or without Sema4D knockout. The expression and localization of Sema4D in CNV were assessed using PCR, Western blot, and immunostaining. Subsequently, the morphological and imaging examinations were used to evaluate the size of CNV and vascular leakage. Finally, the expression of M2 markers, senescence-related markers, and molecules involved in the RhoA/ROCK pathway was detected. Results: We found that Sema4D was predominantly expressed in macrophages within CNV lesions, and both the mRNA and protein levels of Sema4D progressively increased following laser photocoagulation, a trend more pronounced in old mice. Moreover, Sema4D knockout markedly inhibited M2 polarization in senescent macrophages and reduced the size and leakage of CNV, particularly in aged mice. Mechanistically, aging was found to upregulate RhoA/ROCK signaling, and knockout of Sema4D effectively suppressed the activation of this pathway, with more significant effects observed in aged mice. Conclusions: Our findings revealed that the deletion of Sema4D markedly inhibited M2 macrophage polarization through the suppression of the RhoA/ROCK pathway, ultimately leading to the attenuation of senescence-associated CNV. These data indicate that targeting Sema4D could offer a promising approach for gene editing therapy in patients with neovascular age-related macular degeneration.
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Neovascularização de Coroide , Modelos Animais de Doenças , Macrófagos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Semaforinas , Transdução de Sinais , Quinases Associadas a rho , Proteína rhoA de Ligação ao GTP , Animais , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/genética , Neovascularização de Coroide/patologia , Camundongos , Macrófagos/metabolismo , Quinases Associadas a rho/metabolismo , Semaforinas/genética , Semaforinas/metabolismo , Transdução de Sinais/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismo , Antígenos CD/metabolismo , Antígenos CD/genética , Western Blotting , Masculino , AngiofluoresceinografiaRESUMO
Coupling the Si-based anodes with nickel-rich LiNixMnyCo1-x-yO2 cathodes (x ≥ 0.8) in the energy-dense cell prototype suffers from the mechanical instability of the Li-Si alloys, cathode collapse upon the high-voltage cycling, as well as the severe leakage current at elevated temperatures. More seriously, the cathode-to-anode cross-talk effect of transitional metal aggravates the depletion of the active Li reservoir. To reconcile the cation utilization degree, stress dissipation, and extreme temperature tolerance of the Si-based anode||NMC prototype, we propose a gel polymer electrolyte to reinforce the mechanical integrity of Si anode and chelate with the transitional cations towards the stabilized interfacial property. As coupling the conformal gel polymer electrolyte encapsulation with the spatial arranged Si anode and NMC811 cathode, the 2.7 Ah pouch-format cell could achieve the high energy density of 325.9 Wh kg-1 (based on the whole pouch cell), 88.7% capacity retention for 2000 cycles, self-extinguish property as well as a wide temperature tolerance. Therefore, this proposed polymerization strategy provides a leap toward the secured Li batteries.
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Utilizing the high temporal resolution of event-related potentials (ERPs), we compared the time course of processing incongruent color versus 3D-depth information. Participants were asked to judge whether the food color (color condition) or 3D structure (3D-depth condition) was congruent or incongruent with their previous knowledge and experience. The behavioral results showed that the reaction times in the congruent 3D-depth condition were slower than those in the congruent color condition. The reaction times in the incongruent 3D-depth condition were slower than those in the incongruent color condition. The ERP results showed that incongruent color stimuli induced a larger N270, larger P300, and smaller N400 components in the fronto-central region than the congruent color stimuli. Incongruent 3D-depth stimuli induced a smaller N1 in the occipital region, larger P300 and smaller N400 in the parietal-occipital region than congruent 3D-depth stimuli. The time-frequency analysis found that incongruent color stimuli induced a larger theta band (360-580 ms) activation in the fronto-central region than congruent color stimuli. Incongruent 3D-depth stimuli induced larger alpha and beta bands (240-350 ms) activation in the parietal region than congruent 3D-depth stimuli. Our results suggest that the human brain deals with violating general color or depth knowledge in different time courses. We speculate that the depth perception conflict was dominated by solving the problem with visual processing, whereas the color perception conflict was dominated by solving the problem with semantic violation.
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Encéfalo , Percepção de Cores , Percepção de Profundidade , Eletroencefalografia , Potenciais Evocados , Tempo de Reação , Humanos , Masculino , Feminino , Percepção de Cores/fisiologia , Adulto Jovem , Tempo de Reação/fisiologia , Encéfalo/fisiologia , Potenciais Evocados/fisiologia , Percepção de Profundidade/fisiologia , Adulto , Estimulação Luminosa , Fatores de Tempo , Mapeamento EncefálicoRESUMO
Microwave-induced thermoacoustic (TA) imaging (MTAI) combines pulsed microwave excitation and ultrasound detection to provide high contrast and spatial resolution images through dielectric contrast, which holds great promise for clinical applications. However, artifacts caused by microwave dielectric effect will seriously affect the accuracy of MTAI images that will hinder the clinical translation of MTAI. In this work, we propose a deep learning-based method fully dense generative adversarial network (FD-GAN) for removing artifacts caused by microwave dielectric effect in MTAI. FD-GAN adds the fully dense block to the generative adversarial network (GAN) based on the mutual confrontation between generator and discriminator, which enables it to learn both local and global features related to the removal of artifacts and generate high-quality images. The practical feasibility was tested in simulated, experimental data. The results demonstrate that FD-GAN can effectively remove the artifacts caused by the microwave dielectric effect, and shows superiority in denoising, background suppression, and improvement of image distortion. Our approach is expected to significantly improve the accuracy and quality of MTAI images, thereby enhancing the diagnostic accuracy of this innovative imaging technique.
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The normal operation of organelles is critical for tumor growth and metastasis. Herein, an intelligent nanoplatform (BMAEF) is fabricated to perform on-demand destruction of mitochondria and golgi apparatus, which also generates the enhanced photothermal-immunotherapy, resulting in the effective inhibition of primary and metastasis tumor. The BMAEF has a core of mesoporous silica nanoparticles loaded with brefeldin A (BM), which is connected to ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA) and folic acid co-modified gold nanoparticles (AEF). During therapy, the BMAEF first accumulates in tumor cells via folic acid-induced targeting. Subsequently, the schiff base/ester bond cleaves in lysosome to release brefeldin A and AEF with exposed EGTA. The EGTA further captures Ca2+ to block ion transfer among mitochondria, endoplasmic reticulum, and golgi apparatus, which not only induced dysfunction of mitochondria and golgi apparatus assisted by brefeldin A to suppress both energy and material metabolism against tumor growth and metastasis, but causes AEF aggregation for tumor-specific photothermal therapy and photothermal assisted immunotherapy. Moreover, the dysfunction of these organelles also stops the production of BMI1 and heat shock protein 70 to further enhance the metastasis inhibition and photothermal therapy, which meanwhile triggers the escape of cytochrome C to cytoplasm, leading to additional apoptosis of tumor cells.
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Streptomyces has the largest repertoire of natural product biosynthetic gene clusters (BGCs), yet developing a universal engineering strategy for each Streptomyces species is challenging. Given that some Streptomyces species have larger BGC repertoires than others, we proposed that a set of genes co-evolved with BGCs to support biosynthetic proficiency must exist in those strains, and that their identification may provide universal strategies to improve the productivity of other strains. We show here that genes co-evolved with natural product BGCs in Streptomyces can be identified by phylogenomics analysis. Among the 597 genes that co-evolved with polyketide BGCs, 11 genes in the 'coenzyme' category have been examined, including a gene cluster encoding for the cofactor pyrroloquinoline quinone. When the pqq gene cluster was engineered into 11 Streptomyces strains, it enhanced production of 16,385 metabolites, including 36 known natural products with up to 40-fold improvement and several activated silent gene clusters. This study provides an innovative engineering strategy for improving polyketide production and finding previously unidentified BGCs.
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Produtos Biológicos , Família Multigênica , Streptomyces , Produtos Biológicos/metabolismo , Streptomyces/genética , Streptomyces/metabolismo , Policetídeos/metabolismo , Evolução Molecular , Vias Biossintéticas/genética , Filogenia , Engenharia Metabólica/métodosRESUMO
BACKGROUND: The COVID-19 pandemic have impacts on the prevalence of other pathogens and people's social lifestyle. This study aimed to compare the pathogen, allergen and micronutrient characteristics of pediatric inpatients with pneumonia prior to and during the COVID-19 pandemic in a large tertiary hospital in Shanghai, China. METHODS: Patients with pneumonia admitted to the Department of Pediatric Pulmonology of Xinhua Hospital between March-August 2019 and March-August 2020 were recruited. And clinical characteristics of the patients in 2019 were compared with those in 2020. RESULTS: Hospitalizations for pneumonia decreased by 74% after the COVID-19 pandemic. For pathogens, virus, mycoplasma pneumoniae (MP) and mixed infection rates were all much lower in 2020 than those in 2019 (P < 0.01). Regarding allergens, compared with 2019, the positive rates of house dust mite, shrimp and crab were significantly higher in 2020 (P < 0.01). And for micronutrients, the levels of vitamin B2, B6, C and 25-hydroxyvitamin D (25(OH)D) in 2020 were observed to be significantly lower than those in 2019 (P < 0.05). For all the study participants, longer hospital stay (OR = 1.521, P = 0.000), milk allergy (OR = 6.552, P = 0.033) and calcium (Ca) insufficiency (OR = 12.048, P = 0.019) were identified as high-risk factors for severe pneumonia by multivariate analysis. CONCLUSIONS: The number of children hospitalized with pneumonia and incidence of common pathogen infections were both reduced, and that allergy and micronutrient status in children were also changed after the outbreak of the COVID-19 pandemic.
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COVID-19 , Humanos , COVID-19/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Criança , China/epidemiologia , Pré-Escolar , Hospitalização/estatística & dados numéricos , Lactente , SARS-CoV-2 , Pneumonia/epidemiologia , AdolescenteRESUMO
Urolithiasis is closely linked to lifestyle factors. However, the causal relationship and underlying mechanisms remain unclear. This study aims to investigate the relationship between lifestyle factors and the onset of urolithiasis and explore potential blood metabolite mediators and their role in mediating this relationship. In this study, we selected single nucleotide polymorphisms (SNPs) as instrumental variables if they exhibited significant associations with our exposures in genome-wide association studies (GWAS) (p < 5.0 × 10-8). Summary data for urolithiasis came from the FinnGen database, including 8597 cases and 333,128 controls. We employed multiple MR analysis methods to assess causal links between genetically predicted lifestyle factors and urolithiasis, as well as the mediating role of blood metabolites. A series of sensitivity and pleiotropy analyses were also conducted. Our results show that cigarettes smoked per day (odds ratio [OR] = 1.159, 95% confidence interval [CI] = 1.004-1.338, p = 0.044) and alcohol intake frequency (OR = 1.286, 95% CI = 1.056-1.565, p = 0.012) were positively associated with increased risk of urolithiasis, while tea intake (OR = 0.473, 95% CI = 0.299-0.784, p = 0.001) was positively associated with reduced risk of urolithiasis. Mediation analysis identifies blood metabolites capable of mediating the causal relationship between cigarettes smoked per day, tea intake and urolithiasis. We have come to the conclusion that blood metabolites serve as potential causal mediators of urolithiasis, underscoring the importance of early lifestyle interventions and metabolite monitoring in the prevention of urolithiasis.
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Estudo de Associação Genômica Ampla , Urolitíase , Humanos , Análise da Randomização Mendeliana , Estilo de Vida , Urolitíase/etiologia , Urolitíase/genética , CháRESUMO
Typical methods for stable immobilization of proteins often involve time-consuming surface modification of silicon-based materials to enable specific binding, while the nonspecific adsorption method is faster but usually unstable. Herein, we fused a silica-binding protein, Si-tag, to target proteins so that the target proteins could attach directly to silica substrates in a single step, markedly streamlining the immobilization process. The adhesion force between the Si-tag and glass substrates was determined to be approximately 400-600 pN at the single-molecule level by atomic force microscopy, which is greater than the unfolding force of most proteins. The adhesion force of the Si-tag exhibits a slight increase when pulled from the C-terminus compared to that from the N-terminus. Furthermore, the Si-tag's adhesion force on a glass surface is marginally higher than that on a silicon nitride probe. The binding properties of the Si-tag are not obviously affected by environmental factors, including pH, salt concentration, and temperature. In addition, the macroscopic adhesion force between the Si-tag-coated hydrogel and glass substrates was â¼40 times higher than that of unmodified hydrogels. Therefore, the Si-tag, with its strong silica substrate binding ability, provides a useful tool as an excellent fusion tag for the rapid and mechanically robust immobilization of proteins on silica and for the surface coating of silica-binding materials.
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Proteínas de Transporte , Dióxido de Silício , Dióxido de Silício/química , Análise Espectral , Microscopia de Força Atômica , Propriedades de SuperfícieRESUMO
This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.
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Neoplasias Encefálicas , Neoplasias da Mama , Conectoma , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , MedoAssuntos
Cistadenoma Mucinoso , Neoplasias Renais , Humanos , Universidades , Pelve Renal , Neoplasias Renais/cirurgia , ChinaRESUMO
Although previous studies have well established that audiovisual enhancement has a promoting effect on working memory and selective attention, there remains an open question about the influence of audiovisual enhancement on attentional guidance by working memory. To address this issue, the present study adopted a dual-task paradigm that combines a working memory task and a visual search task, in which the content of working memory was presented in audiovisual or visual modalities. Given the importance of search speed in memory-driven attentional suppression, we divided participants into two groups based on their reaction time (RT) in neutral trials and examined whether audiovisual enhancement in attentional suppression was modulated by search speed. The results showed that the slow search group exhibited a robust memory-driven attentional suppression effect, and the suppression effect started earlier and its magnitude was greater in the audiovisual condition than in the visual-only condition. However, among the faster search group, the suppression effect only occurred in the trials with longer RTs in the visual-only condition, and its temporal dynamics were selectively improved in the audiovisual condition. Furthermore, audiovisual enhancement of memory-driven attention evolved over time. These findings suggest that semantically congruent bimodal presentation can progressively facilitate the strength and temporal dynamics of memory-driven attentional suppression, and that search speed plays an important role in this process. This may be due to a synergistic effect between multisensory working memory representation and top-down suppression mechanism. The present study demonstrates the flexible role of audiovisual enhancement on cognitive control over memory-driven attention.