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Topological insulators offer significant potential to revolutionize diverse fields driven by nontrivial manifestations of their topological electronic band structures. However, the realization of superior integration between exotic topological states and superconductivity for practical applications remains a challenge, necessitating a profound understanding of intricate mechanisms. Here, we report experimental observations for a novel superconducting phase in the pressurized second-order topological insulator candidate Ta2Pd3Te5, and the high-pressure phase maintains its original ambient pressure lattice symmetry up to 45 GPa. Our in situ high-pressure synchrotron X-ray diffraction, electrical transport, infrared reflectance, and Raman spectroscopy measurements, in combination with rigorous theoretical calculations, provide compelling evidence for the association between the superconducting behavior and the densified phase. The electronic state change around 20 GPa was found to modify the topology of the Fermi surface directly, which synergistically fosters the emergence of robust superconductivity. In-depth comprehension of the fascinating properties exhibited by the compressed Ta2Pd3Te5 phase is achieved, highlighting the extraordinary potential of topological insulators for exploring and investigating high-performance electronic advanced devices under extreme conditions.
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Improving intuitive eating can effectively prevent emotional eating, restrained eating, and overeating, and help improve people's physical and mental health. Based on the acceptance model of intuitive eating, ecological systems theory, family stress model, and transactional model of stress and coping, the present study aimed to explore the relationship between family cohesion and intuitive eating and its underlying mechanisms through a cross-sectional study design. A random sample of 702 college students from 29 provinces in China, aged from 18 to 26 years (54.56% male, M age = 21.12 years), voluntarily participated in the survey. Demographic variables, family cohesion, intuitive eating, perceived stress, and coping style were measured. The results indicated that family cohesion was significantly positively correlated with intuitive eating and the direct effect between them was significant. Meanwhile, there was a significant indirect effect of family cohesion on intuitive eating through perceived stress and positive coping styles. Moreover, perceived stress and positive coping styles, rather than negative coping styles, acted as serial mediators in the association between family cohesion and intuitive eating. The findings shed light on the prevention and intervention for disordered eating and obesity and provided a new theoretical perspective for the mental health education of college students. In addition, implications and directions for future research were also discussed.
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Adaptação Psicológica , Emoções , Humanos , Masculino , Adulto Jovem , Adulto , Feminino , Estudos Transversais , Ansiedade , Estudantes/psicologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Type 2 diabetes mellitus is a global health problem. It often leads to a decline in the differentiation capacity of myoblasts and progressive loss of muscle mass, which in turn results in deterioration of skeletal muscle function. However, effective therapies against skeletal muscle diseases are unavailable. METHODS: Skeletal muscle mass and differentiation ability were determined in db/+ and db/db mice. Transcriptomics and metabolomics approaches were used to explore the genetic mechanism regulating myoblast differentiation in C2C12 myoblasts. RESULTS: In this study, the relatively uncharacterized solute carrier family gene Slc2a6 was found significantly up-regulated during myogenic differentiation and down-regulated during diabetes-induced muscle atrophy. Moreover, RNAi of Slc2a6 impaired the differentiation and myotube formation of C2C12 myoblasts. Both metabolomics and RNA-seq analyses showed that the significantly differentially expressed genes (e.g., LDHB) and metabolites (e.g., Lactate) during the myogenic differentiation of C2C12 myoblasts post-Slc2a6-RNAi were enriched in the glycolysis pathway. Furthermore, we show that Slc2a6 regulates the myogenic differentiation of C2C12 myoblasts partly through the glycolysis pathway by targeting LDHB, which affects lactic acid accumulation. CONCLUSION: Our study broadens the understanding of myogenic differentiation and offers the Slc2a6-LDHB axis as a potential therapeutic target for the treatment of diabetes-associated muscle atrophy. Video abstract.
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Diabetes Mellitus Tipo 2 , Animais , Diferenciação Celular , Diabetes Mellitus Tipo 2/metabolismo , Camundongos , Desenvolvimento Muscular/genética , Fibras Musculares Esqueléticas/metabolismo , Atrofia Muscular/metabolismo , Mioblastos/metabolismoRESUMO
Chinese hamster ovary (CHO) cell lines are widely used in industry for biological drug production. During cell culture development, considerable effort is invested to understand the factors that greatly impact cell growth, specific productivity and product qualities of the biotherapeutics. While high-throughput omics approaches have been increasingly utilized to reveal cellular mechanisms associated with cell line phenotypes and guide process optimization, comprehensive omics data analysis and management have been a challenge. Here we developed CHOmics, a web-based tool for integrative analysis of CHO cell line omics data that provides an interactive visualization of omics analysis outputs and efficient data management. CHOmics has a built-in comprehensive pipeline for RNA sequencing data processing and multi-layer statistical modules to explore relevant genes or pathways. Moreover, advanced functionalities were provided to enable users to customize their analysis and visualize the output systematically and interactively. The tool was also designed with the flexibility to accommodate other types of omics data and thereby enabling multi-omics comparison and visualization at both gene and pathway levels. Collectively, CHOmics is an integrative platform for data analysis, visualization and management with expectations to promote the broader use of omics in CHO cell research.
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Genômica , Internet , Metabolômica , Proteômica , Animais , Células CHO , Cricetulus , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Análise de Sequência de RNARESUMO
With currently available molecular imaging techniques, hepatocellular carcinoma (HCC), a liver cancer with high mortality rates and poor treatment responses, is mostly diagnosed at its late stage. This is largely due to the lack of highly sensitive contrast agents with high liver specificity. Herein, we report a novel bimodal contrast agent molecule CNCI-1 for the effective detection of HCC at its early stage both in vitro and in vivo. The agent has high liver specificity with effective X-ray computed tomography (CT)/near-infrared (NIR) imaging functions. It has been successfully applied to in vivo NIR imaging with high sensitivity and high selectivity to the HCC region of the HepG2 tumor-xenografted mice model and LM3 orthotopic hepatoma mice model. Moreover, the agent was found to be noninvasive and hepatocarcinoma cells preferential. Furthermore, it also enhanced the tumor imaging by revealing the blood vessels nearby for the CT image acquisition in the VX2 orthotopic hepatoma rabbit model. Our design strategy provides a new avenue to develop the medical relevant bimodal contrast agents for diagnosis of HCC at its early stage.
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Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste/química , Neoplasias Hepáticas/diagnóstico por imagem , Acetanilidas/síntese química , Acetanilidas/química , Acetanilidas/toxicidade , Animais , Carcinoma Hepatocelular/patologia , Meios de Contraste/síntese química , Meios de Contraste/toxicidade , Células Hep G2 , Humanos , Indóis/síntese química , Indóis/química , Indóis/toxicidade , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Coelhos , Tomografia Computadorizada por Raios XRESUMO
In China, the rate of spicy food consumption is rising, and chili pepper is among the most popular spicy foods consumed nationwide. Therefore, investigation into spicy food craving is of public health interest and can also provide better insights into the mechanisms that underlie food cravings more generally. This exploratory study aimed to determine neural circuits underlying spicy food craving by comparing brain response to the cues of foods containing chili peppers in extreme cravers and non-cravers defined by scores on the Spicy Food Craving Questionnaire. A group of extreme cravers (nâ¯=â¯25) and a group of age- and sex-matched non-cravers (nâ¯=â¯26) participated in an fMRI event-related cue-reactivity paradigm, during which pictures of foods with visible chili peppers and pictures of foods with no chili peppers were presented. Results showed that extreme spicy food cravers exhibited increased activation in bilateral insula, left putamen, left dorsal anterior cingulate cortex, right inferior parietal lobule, right lingual gyrus, bilateral cuneus, left precuneus, left fusiform gyrus, and right precentral gyrus compared to non-cravers when exposed to the cues of foods containing chili versus foods without chili. While we did not observe the differential activation of orbitofrontal cortex and amygdala of this contrast in extreme cravers compared to non-cravers. Changes in beta values within the right insula, left putamen, left dorsal anterior cingulate cortex and left precuneus were positively associated with subjective spicy food craving during the scan among extreme cravers. In addition, changes in beta values within right inferior parietal lobule was significantly correlated with the frequency of spicy food intake among extreme cravers. These results align with prior work suggesting that the dorsal striatum, the anterior cingulate cortex and the insula underlie food craving.
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Capsicum , Fissura/fisiologia , Comportamento Alimentar/fisiologia , Imageamento por Ressonância Magnética , Ritmo beta/fisiologia , Encéfalo/fisiologia , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , China , Sinais (Psicologia) , Feminino , Alimentos , Análise de Alimentos , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Humanos , Masculino , Estimulação Luminosa , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Paladar/fisiologia , Adulto JovemRESUMO
Is our food safe and free of the crisis of antibiotics and antibiotic resistance (AR)? And will the derived food waste (FW) impose AR risk to the environment after biological treatment? This study used restaurant FW leachates flowing through a 200â¯tons-waste/day biological treatment plant as a window to investigate the fate of antibiotics and antibiotic-resistance genes (ARGs) during the acceptance and treatment of FW. Sulfonamides (sulfamethazine, sulfamethoxazole) and quinolones (ciprofloxacin, enrofloxacin, ofloxacin) were detected during FW treatment, while tetracyclines, macrolides and chloramphenicols were not observable. ARGs encoding resistance to sulfonamides, tetracyclines and macrolides emerged in FW leachates. Material flow analysis illustrated that the total amount of antibiotics (except sulfamethazine) and ARGs were constant during FW treatment processes. Both the concentration and total amount of most antibiotics and ARGs fluctuated during treatment, physical processes (screening, centrifugation, solid-liquid and oil-water separation) did not decrease antibiotic or ARGs concentrations or total levels permanently; the affiliated wastewater treatment plant appeared to remove sulfonamides and most ARGs concentrations and total amount. Heavy metals Ni, Co and Cu were important for disseminating antibiotics concentrations and MGEs for distributing ARGs concentrations. Humic substances (fulvic acids, hydrophilic fractions), C-associated and N-associated contents were essential for the distribution of the total amounts of antibiotics and ARGs. Overall, this study implied that human food might not be free of antibiotics and ARGs, and FW was an underestimated AR pool with various determinants. Nonetheless, derived hazards of FW could be mitigated through biological treatment with well-planned daily operations.
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Antibacterianos/análise , Resistência Microbiana a Medicamentos/genética , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/análise , Genes Bacterianos , Metais Pesados/análise , Restaurantes , Águas Residuárias/química , Águas Residuárias/microbiologiaRESUMO
As the development of sequencing technology, more and more circular RNAs (circRNAs) are identified in human cancer tissues. Increasing evidences imply circRNAs are important regulators in tumor progression. Nevertheless, how circRNAs participate in breast cancer development and progression is not well understood. In the present study, we identified a novel circRNA hsa_circ_0008039 with upregulated expression level in breast cancer tissues. By functional experiments, we found that hsa_circ_0008039 depletion significantly suppressed the proliferation, arrested cell-cycle progression and reduced migration in breast cancer. Mechanistic investigations suggested that hsa_circ_0008039 served as a competing endogenous RNA (ceRNA) of miR-432-5p. Subsequently, E2F3 was identified as the functional target of miR-432-5p and overexpression of hsa_circ_0008039 elevated E2F3 expression in breast cancer. On the whole, our study indicated that hsa_circ_0008039 exerted oncogenic roles in breast cancer and suggested the hsa_circ_0008039/miR-432-5p/E2F3 axis might be a potential therapeutic target.
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Neoplasias da Mama/genética , Fator de Transcrição E2F3/genética , MicroRNAs/genética , RNA/genética , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Fator de Transcrição E2F3/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Oncogenes , RNA/antagonistas & inibidores , RNA/metabolismo , RNA Circular , Regulação para CimaRESUMO
Epidemiological studies have evaluated the risk of bladder cancer (BCa) in relation to total fluid intake, as well as specific type of beverages consumption, with controversial results. The aim of this study was to further explore the potential relationship by conducting a meta-analysis. Fifty-four articles involving more than 43,000 BCa patients were included in this meta-analysis. A positive, though not statistically significant, association was found between total fluid intake and risk of BCa comparing the highest with lowest intake (SRRE: 1.16, 95%CI: 1.00-1.36). By conducting dose-response meta-analysis, we found that each 500 ml/day increase in total fluid intake was associated with 3.3% increased risk of BCa (RR: 1.03, 95%CI: 1.00-1.07). Pronounced increase in risk of BCa was detected when total fluid intake was more than 3000 ml/day. Meta-analyses of specific type of beverages showed increasing intake of coffee (RR: 1.03, 95%CI: 1.02-1.05) were risk factors for BCa. On the contrary, increasing intake of milk appeared to be a potential protective factor for BCa (RR: 0.90, 95%CI: 0.83-0.98). The risk of BCa was not significantly related to intake of water (RR: 1.01, 95%CI: 0.98-1.03), alcohol (RR: 1.01, 95%CI: 0.97-1.05), tea (RR: 1.01, 95%CI: 0.97-1.05) and soft drinks (RR: 1.04, 95%CI: 0.96-1.11).
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Bebidas , Neoplasias da Bexiga Urinária/etiologia , Café , Ingestão de Líquidos , Comportamento de Ingestão de Líquido , Humanos , Estudos Observacionais como Assunto , Fatores de Risco , CháRESUMO
BACKGROUND: Protein secretion to the periplasm of Escherichia coli offers an attractive route for producing heterologous proteins including antibodies. In this approach, a signal peptide is fused to the N-terminus of the heterologous protein. The signal peptide mediates translocation of the heterologous protein from the cytoplasm to the periplasm and is cleaved during the translocation process. It was previously shown that optimization of the translation initiation region (TIR) which overlaps with the nucleotide sequence of the signal sequence improves the production of heterologous proteins. Despite the progress, there is still room to improve yields using secretion as a means to produce protein complexes such as full-length monoclonal antibodies (mAbs). RESULTS: In this study we identified the inefficient secretion of heavy chain as the limitation for full-length mAb accumulation in the periplasm. To improve heavy chain secretion we investigated the effects of various signal peptides at controlled TIR strengths. The signal peptide of disulfide oxidoreductase (DsbA) mediated more efficient secretion of heavy chain than the other signal peptides tested. Mutagenesis studies demonstrated that at controlled translational levels, hydrophobicity of the hydrophobic core (H-region) of the signal peptide is a critical factor for heavy chain secretion and full-length mAb accumulation in the periplasm. Increasing the hydrophobicity of a signal peptide enhanced heavy chain secretion and periplasmic levels of assembled full-length mAbs, while decreasing the hydrophobicity had the opposite effect. CONCLUSIONS: This study demonstrates that under similar translational strengths, the hydrophobicity of the signal peptide plays an important role in heavy chain secretion. Increasing the hydrophobicity of the H-region and controlling TIR strengths can serve as an approach to improve heavy chain secretion and full-length mAb production in E. coli.
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Anticorpos/metabolismo , Engenharia de Proteínas/métodos , Sinais Direcionadores de Proteínas , Sequência de Aminoácidos , Anticorpos Monoclonais/metabolismo , Escherichia coli/metabolismo , Escherichia coli/ultraestrutura , Interações Hidrofóbicas e Hidrofílicas , Cadeias Pesadas de Imunoglobulinas/metabolismo , Corpos de Inclusão/metabolismo , Corpos de Inclusão/ultraestrutura , Dados de Sequência Molecular , Iniciação Traducional da Cadeia Peptídica , Periplasma/metabolismoRESUMO
Emotional false memories are the erroneous recollection of events accompanied by an emotional experience. In high-risk domains like psychotherapy and the legal system, emotional false memories are of particular importance. Despite the systematic research conducted on emotional false memories in recent years, findings remain contradictory. Some studies have suggested that negative emotion reduces false memories, while others have suggested that negative emotion increases false memories. Research has mainly employed words and pictures as experimental stimuli, and studies using both types of memory stimuli are reviewed here. From this examination, it emerged that the main reasons for contradictory findings are as follows: (1) different materials have varying effects on inducing false memories, with pictures demonstrating a memory advantage compared to words; (2) recall and recognition tests have been used interchangeably, leading to different false-memory effects depending on the memory test employed; and (3) different studies have adopted different levels of control over valence and arousal when manipulating emotional variables. Future studies should distinguish between the use of different memory materials, examine specific differences in recall and recognition tests, and measure the impact of specific emotions on false memory beyond the dimensions of valence and arousal.
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In China, the rate of spicy food consumption is rising, and chili pepper is among the most popular spicy foods consumed nationwide. However, little effort has been made to understand the mechanism behind spicy food craving. This exploratory study aimed to investigate differences in insula-based resting state functional connectivity (rsFC) between spicy food cravers and non-cravers, and the association between rsFC, impulsivity and spicy food craving. A group of extreme cravers (n = 49) and a group of age- and sex-matched non-cravers (n = 46) completed a resting-state fMRI scan, during which participants were instructed to keep their eyes closed, to not think of anything in particular, and to remain awake. Participants completed the Spicy Food Craving Questionnaire, Barratt Impulsiveness Scale, Sensation Seeking Scale and Positive and Negative Affect Schedule, and rated the frequency of spicy food intake. Results revealed increased insula-occipital lobe resting-state functional connectivity in individuals with spicy food cravings, and the positive correlations between insula-middle occipital gyrus rsFC, impulsivity and spicy food craving. Specifically, the insula-middle occipital gyrus rsFC strength mediated the relationship between the motor impulsivity and spicy food craving. It is hoped that our exploratory findings may shed new insights into the neural mechanisms of spicy food craving and motivate further exploration of spicy food craving in diverse contexts and cultures.
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Laser cladding provides advanced surface treatment capabilities for enhancing the properties of components. However, its effectiveness is often challenged by the formation of hot cracks during the cladding process. This study focuses on the formation mechanism and inhibition of hot cracks in a novel cobalt-based alloy (K688) coating applied to 304LN stainless steel via laser cladding. The results indicate that hot crack formation is influenced by liquid film stability, the stress concentration, and precipitation phases. Most hot cracks were found at 25°-45° high-angle grain boundaries (HAGBs) due to the high energy of these grain boundaries, which stabilize the liquid film. A flat-top beam, compared to a Gaussian beam, creates a melt pool with a lower temperature gradient and more mitigatory fluid flow, reducing thermal stresses within the coating and the fraction of crack-sensitive, high-angle grain boundaries (S-HAGBs). Finally, crack formation was significantly inhibited by utilizing a flat-top laser beam to optimize the process parameters. These findings provide a technical foundation for achieving high-quality laser cladding of dissimilar materials, offering insights into optimizing process parameters to prevent hot crack formation.
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The resource recovery and reuse of precious metal-laden wastewater is widely recognized as crucial for sustainable development. Superalloy electrolytes, produced through the electrolysis of superalloy scrap, contain significant quantities of precious metal ions, thereby possessing substantial potential for recovery value. This study first explores the feasibility of utilizing fungi to treat Superalloy electrolytes. Five fungi resistant to high concentrations of heavy metals in electrolytes (mainly containing Co, Cr, Mo, Re, and Ni) were screened from the soil of a mining area to evaluate their adsorption characteristics. All five fungi were identified by ITS sequencing, and among them, Paecilomyces lilacinus showed the best adsorption performance for the five heavy metals; therefore, we conducted further research on its adsorption characteristics. The best adsorption effect of Co, Cr, Mo, Re, and Ni was 37.09, 64.41, 47.87, 41.59, and 25.38%, respectively, under the conditions of pH 5, time 1 h, dosage 26.67 g/L, temperature 25-30°C, and an initial metal concentration that was diluted fivefold in the electrolyte. The biosorption of Co, Mo, Re, and Ni was better matched by the Langmuir model than by the Freundlich model, while Cr displayed the opposite pattern, showing that the adsorption process of P. lilacinus for the five heavy metals is not a single adsorption mechanism, but may involve a multi-step adsorption process. The kinetics study showed that the quasi-second-order model fitted better than the quasi-first-order model, indicating that chemical adsorption was the main adsorption process of the five heavy metals in P. lilacinus. Fourier transform infrared spectroscopy revealed that the relevant active groups, i.e., hydroxyl (-OH), amino (-NH2), amide (- CONH2), carbonyl (-C = O), carboxyl (-COOH), and phosphate (PO43-), participated in the adsorption process. This study emphasized the potential application of P. lilacinus in the treatment of industrial wastewater with extremely complex background values.
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Although the impact of SARS-CoV-2 in the lung has been extensively studied, the molecular regulators and targets of the host-cell programs hijacked by the virus in distinct human airway epithelial cell populations remain poorly understood. This is in part ascribed to the use of non-primary cell systems, overreliance on single-cell gene expression profiling that not ultimately reflect protein activity and bias toward the downstream effects rather than their mechanistic determinants. Here we address these issues by network-based analysis of single cell transcriptomic profiles of pathophysiologically relevant human adult basal, ciliated and secretory cells to identify master regulator (MR) protein modules controlling their SARS-CoV-2-mediated reprogramming. This uncovered chromatin remodeling, endosomal sorting, ubiquitin pathway as well as proviral factors identified by CRISPR analyses as components of the host response collectively or selectively activated in these cells. Large-scale perturbation assays, using a clinically-relevant drug library, identified 11 drugs able to invert the entire MR signature activated by SARS-CoV-2 in these cell types. Leveraging MR analysis and perturbational profiles of human primary cells, represents a novel mechanism-based approach and resource that can be directly generalized to interrogate signatures of other airway conditions for drug prioritization.
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Amyloids are highly aggregated proteinaceous fibers historically associated with neurodegenerative conditions including Alzheimers, Parkinsons, and prion-based encephalopathies. Polymerization of amyloidogenic proteins into ordered fibers can be accelerated by preformed amyloid aggregates derived from the same protein in a process called seeding. Seeding of disease-associated amyloids and prions is highly specific and cross-seeding is usually limited or prevented. Here we describe the first study on the cross-seeding potential of bacterial functional amyloids. Curli are produced on the surface of many Gram-negative bacteria where they facilitate surface attachment and biofilm development. Curli fibers are composed of the major subunit CsgA and the nucleator CsgB, which templates CsgA into fibers. Our results showed that curli subunit homologs from Escherichia coli, Salmonella typhimurium LT2, and Citrobacter koseri were able to cross-seed in vitro. The polymerization of Escherichia coli CsgA was also accelerated by fibers derived from a distant homolog in Shewanella oneidensis that shares less than 30% identity in primary sequence. Cross-seeding of curli proteins was also observed in mixed colony biofilms with E. coli and S. typhimurium. CsgA was secreted from E. coli csgB- mutants assembled into fibers on adjacent S. typhimurium that presented CsgB on its surfaces. Similarly, CsgA was secreted by S. typhimurium csgB- mutants formed curli on CsgB-presenting E. coli. This interspecies curli assembly enhanced bacterial attachment to agar surfaces and supported pellicle biofilm formation. Collectively, this work suggests that the seeding specificity among curli homologs is relaxed and that heterogeneous curli fibers can facilitate multispecies biofilm development.
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Amiloide/metabolismo , Proteínas de Bactérias/metabolismo , Estruturas Bacterianas/metabolismo , Biofilmes/crescimento & desenvolvimento , Citrobacter koseri/fisiologia , Escherichia coli/fisiologia , Salmonella typhimurium/fisiologia , Amiloide/genética , Aderência Bacteriana/fisiologia , Proteínas de Bactérias/genética , Estruturas Bacterianas/genética , MutaçãoRESUMO
Amyloid fibers are filamentous protein structures commonly associated with neurodegenerative diseases. Unlike disease-associated amyloids, which are the products of protein misfolding, Escherichia coli assemble membrane-anchored functional amyloid fibers called curli. Curli fibers are composed of two proteins, CsgA and CsgB. In vivo, the polymerization of the major curli subunit protein, CsgA, is dependent on CsgB-mediated nucleation. The amyloid core of CsgA features five imperfect repeats (R1-R5), and R1 and R5 govern CsgA responsiveness to CsgB nucleation and self-seeding by CsgA fibers. Here, the specificity of bacterial amyloid nucleation was probed, revealing that certain aspartic acid and glycine residues inhibit the intrinsic aggregation propensities and nucleation responsiveness of R2, R3, and R4. These residues function as "gatekeepers" to modulate CsgA polymerization efficiency and potential toxicity. A CsgA molecule lacking gatekeeper residues polymerized in vitro significantly faster than wild-type CsgA and polymerized in vivo in the absence of the nucleation machinery, resulting in mislocalized fibers. This uncontrolled polymerization was associated with cytotoxicity, suggesting that incorrectly regulated CsgA polymerization was detrimental to the cell.
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Sequência de Aminoácidos , Amiloide/biossíntese , Proteínas de Escherichia coli , Subunidades Proteicas/genética , Amiloide/química , Amiloide/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Dados de Sequência Molecular , Conformação Proteica , Dobramento de Proteína , Subunidades Proteicas/metabolismo , Alinhamento de SequênciaRESUMO
In China, the rate of spicy food consumption is rising, and chili pepper is among the most popular spicy foods consumed nationwide. According to the 'cued overeating' model, visual and olfactory cues of food can lead to changes in physiological responses and increase the likelihood and amount of food intake. However, no studies have explored the role of spicy food cues in cue reactivity among spicy food cravers. The exploratory study aimed to investigate cue-induced physiological responses, subjective cravings, eating behaviors and their associations in spicy food cravers. A group of spicy cravers (n = 59) and a group of age- and sex-matched non-cravers (n = 60) were exposed to food cues that contained or did not contain chili, during which physiological responses and food consumption were measured. The results revealed that spicy food cravers showed increased salivation and heart rate in response to food cues that contained chili compared to cues without chili and consumed significantly more chili oil after chili exposure. For cravers, heart rate during chili exposure was positively correlated with changes in subjective spicy food craving, and increases in subjective spicy food craving during chili exposure positively predicted subsequent chili oil consumption. The current exploratory study confirms the 'cued overeating' model and extends previous findings on food cravings, showing that even though chili peppers can elicit aversive oral burns and pain, they share the same physiological mechanism underlying cue reactivity as other kinds of cravings.
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Fissura , Sinais (Psicologia) , Humanos , Fissura/fisiologia , Alimentos , Comportamento Alimentar , HiperfagiaRESUMO
BACKGROUND: microRNA-628-5p (miR-628-5p) has a significant impact on certain types of cancer. The precise function of miR-628-5p in the context of bladder urothelial carcinoma (BLCA) remains ambiguous. OBJECTIVE: We aimed to investigate the role of miR-628-5p in BLCA. METHODS: The samples were collected from The Cancer Genome Atlas (TCGA). Statistics were employed to evaluate the correlation and predictive significance of miR-628-5p. We analyzed the target genes and regulatory network of miR-628-5p and the correlation between miR-628-5p and immune infiltration. The expression of miR-628-5p in BLCA cells was confirmed by quantitative reverse-transcription PCR (qRT-PCR). RESULTS: miR-628-5p exhibited differential expression across various types of cancer. There was a significant association between high expression of miR-628-5p and primary therapy outcome (p < 0.05). High expression of miR-628-5p was observed to be associated with poorer overall survival (HR: 1.42; 95% CI: 1.06-1.90; p = 0.02), progress free survival (HR: 1.57; 95% CI: 1.17-2.11; p = 0.003), and disease specific survival (HR: 1.83; 95% CI: 1.28-2.62; p = 0.001) in BLCA. miR-628-5p was an independent prognostic factor in BLCA and may be involved in the development of the disease through various pathways, including focal adhesion, ECM-receptor interaction, PI3K-Akt signaling pathway, and MAPK signaling pathway, and among others. miR-628-5p expression was significantly correlated with immune infiltration in BLCA patients. Compared to normal bladder epithelial cells, BLCA cell lines exhibited a significant upregulation of miR-628-5p. CONCLUSION: It is possible that miR-628-5p could serve as a hopeful therapeutic target and prognostic biomarker for individuals with BLCA.
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Carcinoma de Células de Transição , MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Fosfatidilinositol 3-Quinases , Bexiga Urinária , Biomarcadores , Prognóstico , MicroRNAs/genéticaRESUMO
A novel fourth-generation nickel-based single crystal superalloy was brazed with Co-based filler alloy. The effects of post-weld heat treatment (PWHT) on the microstructure and mechanical properties of brazed joints were investigated. The experimental and CALPHAD simulation results show that the non-isothermal solidification zone was composed of M3B2, MB-type boride and MC carbide, and the isothermal solidification zone was composed of γ and γ' phases. After the PWHT, the distribution of borides and the morphology of the γ' phase were changed. The change of the γ' phase was mainly attributed to the effect of borides on the diffusion behavior of Al and Ta atoms. In the process of PWHT, stress concentration leads to the nucleation and growth of grains during recrystallization, thus forming high angle grain boundaries in the joint. The microhardness was slightly increased compared to the joint before PWHT. The relationship between microstructure and microhardness during the PWHT of the joint was discussed. In addition, the tensile strength and stress fracture life of the joints were significantly increased after the PWHT. The reasons for the improved mechanical properties of the joints were analyzed and the fracture mechanism of the joints was elucidated. These research results can provide important guidance for the brazing work of fourth-generation nickel-based single crystal superalloy.