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Tropomyosin (TM) is the main allergen in shrimp (Litopenaeus vannamei). In this study, the effects of allergenicity and structure of TM by glycosylation (GOS-TM), phosphate treatment (SP-TM), and glycosylation combined with phosphate treatment (GOS-SP-TM) were investigated. Compared to GOS-TM and SP-TM, the IgG/IgE binding capacity of GOS-SP-TM was significantly decreased with 63.9 ± 2.0 and 49.7 ± 2.7%, respectively. Meanwhile, the α-helix content reduced, surface hydrophobicity increased, and 10 specific amino acids (K30, K38, S39, K48, K66, K74, K128, K161, S210, and K251) were modified by glycosylation on six IgE linear epitopes of GOS-SP-TM. In the BALB/c mice allergy model, GOS-SP-TM could significantly reduce the levels of specific IgE, IgG1, and CD4+IL-4+, while the levels of IgG2a, CD4+CD25+Foxp3+, and CD4+IFN-γ+ were increased, which equilibrated Th1 and Th2 cells, thus alleviating allergic symptoms. These results indicated that glycosylation combined with phosphate treatment can provide a new insight into developing hypoallergenic shrimp food.
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Alérgenos , Imunoglobulina E , Penaeidae , Fosfatos , Tropomiosina , Animais , Feminino , Humanos , Camundongos , Alérgenos/imunologia , Alérgenos/química , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/química , Hipersensibilidade Alimentar/imunologia , Glicosilação , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/química , Camundongos Endogâmicos BALB C , Penaeidae/imunologia , Penaeidae/química , Fosfatos/química , Frutos do Mar/análise , Hipersensibilidade a Frutos do Mar/imunologia , Células Th2/imunologia , Células Th2/efeitos dos fármacos , Tropomiosina/imunologia , Tropomiosina/químicaRESUMO
Short chain fatty acids (SCFAs), mainly including acetate, propionate and butyrate, are produced by intestinal bacteria during the fermentation of partially digested and indigestible polysaccharides. SCFAs play an important role in regulating intestinal energy metabolism and maintaining the homeostasis of the intestinal environment and also play an important regulatory role in organs and tissues outside the gut. In recent years, many studies have shown that SCFAs can regulate inflammation and affect host health, and two main signaling mechanisms have also been identified: the activation of G-protein coupled receptors (GPCRs) and inhibition of histone deacetylase (HDAC). In addition, a growing body of evidence highlights the importance of every SCFA in influencing health maintenance and disease development. In this review, we summarized the recent advances concerning the biological properties of SCFAs and their signaling pathways in inflammation and body health. Hopefully, it can provide a systematic theoretical basis for the nutritional prevention and treatment of human diseases.
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Ácidos Graxos Voláteis , Inflamação , Humanos , Ácidos Graxos Voláteis/metabolismo , Inflamação/metabolismo , Animais , Transdução de Sinais , Microbioma Gastrointestinal , Receptores Acoplados a Proteínas G/metabolismo , Metabolismo EnergéticoRESUMO
Surface plasmons excited via inelastic tunnelling have led to plasmon light sources with small footprints and ultrafast response speeds, which are favored by integrated optical circuits. Self-assembled monolayers of organic molecules function as highly tunable tunnel barriers with novel functions. However, limited by the low effective contact between the liquid metal electrode and the self-assembled monolayers, it is quite challenging to obtain molecular plasmon light sources with high density and uniform emission. Here, by combining lithographic patterning with a solvent treatment method, we have demonstrated electrically driven deterministic plasmon emission from arrays of molecular tunnel junctions. The solvent treatment could largely improve the effective contact from 9.6% to 48% and simultaneously allow the liquid metal to fill into lithographically patterned micropore structures toward deterministic plasmon emission with desired patterns. Our findings open up new possibilities for tunnel junction-based plasmon light sources, laying the foundation for electrically driven light-emitting metasurfaces.
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What is already known about this topic?: Chlorinated organophosphate flame retardants (Cl-OPFRs) are frequently detected chemicals in the environment and biological samples, yet there is a lack of systematic evaluation regarding the adverse effects and toxicological mechanisms of Cl-OPFRs. What is added by this report?: This study utilizes the adverse outcome pathway (AOP) framework to assess the health implications and mechanisms of Cl-OPFRs, identifying multi-system toxicity, with a particular emphasis on reproductive issues and the possible toxic mechanisms. What are the implications for public health practice?: These results enhance knowledge of the health hazards linked to Cl-OPFRs, supporting the creation of focused risk evaluations and suitable regulatory actions.
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Depression is a common non-motor symptom of Parkinson's disease. Previous studies demonstrated that hydroxysafflor yellow A had properties of improving motor symptoms of Parkinson's disease. The effect of hydroxysafflor yellow A on depression in Parkinson's disease mice is investigated in this study. To induce Parkinson's disease model, male Swiss mice were exposed to rotenone (30 mg/kg) for 6 weeks. The chronic unpredictable mild stress was employed to induce depression from week 3 to week 6. Sucrose preference, tail suspension, and forced swimming tests were conducted. Golgi and Nissl staining of hippocampus were carried out. The levels of dopamine, 5-hydroxytryptamine and the expression of postsynaptic density protein 95, brain-derived neurotrophic factor in hippocampus were assayed. It showed that HSYA improved the depression-like behaviors of Parkinson's disease mice. Hydroxysafflor yellow A attenuated the injury of nerve and elevated contents of dopamine, 5-hydroxytryptamine in hippocampus. Treatment with hydroxysafflor yellow A also augmented the expression of postsynaptic density protein 95 and brain-derived neurotrophic factor. These findings suggest that hydroxysafflor yellow A ameliorates depression-like behavior in Parkinson's disease mice through regulating the contents of postsynaptic density protein 95 and brain-derived neurotrophic factor, therefore protecting neurons and neuronal dendrites of the hippocampus.
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Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo , Chalcona , Depressão , Hipocampo , Quinonas , Serotonina , Animais , Quinonas/farmacologia , Quinonas/uso terapêutico , Chalcona/análogos & derivados , Chalcona/farmacologia , Chalcona/uso terapêutico , Masculino , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Comportamento Animal/efeitos dos fármacos , Serotonina/metabolismo , Dopamina/metabolismo , Rotenona/farmacologia , Modelos Animais de Doenças , Proteína 4 Homóloga a Disks-Large/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/psicologiaRESUMO
Here we present a sketch of the whole-genome sequence of Pseudomonas benzopyrenica. The strain comes from the leaf veins of a diseased tobacco plant. This study has significant research implications for gaining insights into the characteristics of microorganisms belonging to the genus Pseudomonas.
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To fulfil the demands of rapid proliferation, tumour cells undergo significant metabolic alterations. Suppression of hyperactivated metabolism has been proven to counteract tumour growth. However, whether the reactivation of downregulated metabolic pathways has therapeutic effects remains unexplored. Here we report a nutrient-based metabolic reactivation strategy for effective melanoma treatment. L-Tyrosine-oleylamine nanomicelles (MTyr-OANPs) were constructed for targeted supplementation of tyrosine to reactivate melanogenesis in melanoma cells. We found that reactivation of melanogenesis using MTyr-OANPs significantly impeded the proliferation of melanoma cells, primarily through the inhibition of glycolysis. Furthermore, leveraging melanin as a natural photothermal reagent for photothermal therapy, we demonstrated the complete eradication of tumours in B16F10 melanoma-bearing mice through treatment with MTyr-OANPs and photothermal therapy. Our strategy for metabolism activation-based tumour treatment suggests specific nutrients as potent activators of metabolic pathways.
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Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other metabolic diseases. Recent evidence suggests that modulating adipose tissue to adaptive thermogenesis may offer therapeutic potential for MetS. Xiasangju (XSJ) is a marketed drug and dietary supplement used for the treatment of metabolic disease with anti-inflammatory activity. This study investigated the therapeutic effects of XSJ and the underlying mechanisms affecting the activation of brown adipose tissue (BAT) in MetS. The results revealed that XSJ ameliorated MetS by enhancing glucose and lipid metabolism, leading to reduced body weight and abdominal circumference, decreased adipose tissue and liver index, and improved blood glucose tolerance. XSJ administration stimulated catecholamine biosynthesis, increasing noradrenaline (NA) levels and activating NA-mediated proteins in BAT. Thus, BAT enhanced thermogenesis and oxidative phosphorylation (OXPHOS). Moreover, XSJ induced changes in gut microbiota composition, with an increase in Oscillibacter abundance and a decrease in Bilophila, Candidatus Stoquefichus, Holdemania, Parasutterella and Rothia. XSJ upregulated the proteins associated with intestinal tight junctions corresponding with lower serum lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α) monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) levels to maintain NA signaling transport. In summary, XSJ may alleviate MetS by promoting thermogenesis in BAT to ultimately boost energy metabolism through increasing NA biosynthesis, strengthening intestinal barrier integrity and reducing low-grade inflammation. These findings suggest XSJ has potential as a natural therapeutic agent for the treatment of MetS.
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BACKGROUND: Senior nursing students' perceptions of their professional preparedness help them for expectations of their future nursing role with more confidence, and professional identity may contribute to cultivating nursing students' perceptions of professional preparedness. In this study we applied latent profile analysis to identify the latent profiles of perceived professional preparedness among senior nursing students and to examine their identity and predictors. METHODS: This was a cross-sectional descriptive study. A total of 319 senior nursing students from five universities in China were enrolled. Data were collected using the Perceived Professional Preparedness of Senior Nursing Students' Questionnaire and the Professional Identity Scale for Nursing Students. RESULTS: Three latent profiles were identified and labeled as "low perceived professional preparedness" (n = 90, 28.2%), "low clinical competency-low EBP (Evidence-Based Practice)" (n = 190, 59.5%), and "high perceived professional preparedness" (n = 39, 12.2%). Place of residence, average clinical practicum hours per day, part-time experience, good relationships with classmates, and feeling nobility toward nursing due to COVID-19 significantly predicted profile membership. The average professional identity score was also statistically different across the three profiles (F = 54.69, p < 0.001). CONCLUSIONS: Senior nursing students' perceptions of their professional preparedness were divided into three profiles, and out results show that promoting professional identity may effectively foster their perceived professional preparedness. This study therefore highlights the importance of targeted interventions by considering their distinct perceptions of professional preparedness patterns.
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Glucosylglycerate (R-2-O-α-D-glucopyranosyl-glycerate, GG) is a negatively charged compatible solution with versatile functions. Here, an artificial in vitro enzymatic cascade was designed to feasibly and sustainably produce GG from affordable starch and glycerol. First, Spirochaeta thermophila glucosylglycerate phosphorylase (GGP) was carefully selected because of its excellent heterologous expression, specific activity, and thermostability. The optimized two-enzyme cascade, consisting of alpha-glucan phosphorylase (αGP) and GGP, achieved a remarkable 81 % conversion rate from maltodextrin and D-glycerate. Scaling up this cascade resulted in a practical concentration of 58 g/L GG with a 62 % conversion rate based on the added D-glycerate. Additionally, the production of GG from inexpensive starch and glycerol in one-pot using artificial four-enzyme cascade was successfully implemented, which integrates alditol oxidase and catalase with αGP and GGP. Collectively, this sustainable enzymatic cascade demonstrates the feasibility of the practical synthesis of GG and has the potential to produce other glycosides using the phosphorylase-and-phosphorylase paradigm.
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Glicerol , Amido , Glucosídeos/metabolismo , Fosforilases/metabolismoRESUMO
This quasi-experimental study investigated the impact of traditional Chinese culture-based life-and-death education on 38 ICU nurses. Participants underwent 14 hours of training, and data were collected before and after the intervention using various questionnaires. Frequency and percentage were used for categorical data; mean and standard deviation for measurement data; and paired-sample t test for comparison of teaching effects before and after the intervention of life-and-death education programs. Results indicated significant improvements in understanding of death, reduced death anxiety, enhanced death coping abilities, and increased search for meaning (p < .05). However, there was no statistically significant change in attitude toward death (p > .05). Life-and-death education rooted in traditional Chinese culture positively influenced ICU nurses, fostering improved death cognition, reduced death anxiety, enhanced coping skills, and a heightened sense of meaning in life. Subsequent research will explore the relationship and distinctions between explicit and implicit death attitudes.
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The phase inversion tape casting has been widely used to fabricate open straight porous supports for solid oxide fuel cells (SOFCs), which can offer better gas transmission and minimize the concentration polarization. However, the overall weak strength of the macro-porous structure still limits the applications of these SOFCs. In this work, a novel SOFC supported by an ordered porous cathode membrane with a four-layer configuration containing a finger-like porous 3 mol% yttria- stabilized zirconia (3YSZ)-La0.8Sr0.2Co0.6Fe0.4O3-δ (LSCF) catalyst, porous 8 mol% yttria-stabilized zirconia (8YSZ)-LSCF catalyst, and dense 8YSZ porous 8YSZ-NiO catalyst is successfully prepared by the phase inversion tape casting, dip-coating, co-sintering, and impregnation process. The flexural strength of the open straight porous 3YSZ membrane is as high as 131.95 MPa, which meets the requirement for SOFCs. The cathode-supported single cell shows a peak power density of 540 mW cm-2 at 850 °C using H2 as the fuel. The degradation mechanism of the SOFC is investigated by the combination of microstructure characterization and distribution of relaxation times (DRT) analysis.
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Introduction: Patriotism, a positive emotional attachment to one's country, has been associated with prosocial behavior, social responsibility, and gratitude. It plays a crucial role in promoting social harmony and national development. However, the factors influencing patriotism and their mechanisms remain unclear. This research consists of two studies exploring the internal mechanisms that connect gratitude and patriotism. Methods: Study 1 conducted a cross-sectional analysis among 3,826 college students to investigate the influence of gratitude on patriotism, emphasizing the mediating role of general life satisfaction and the moderating impact of socioeconomic status. This approach aimed to elucidate the complex relationships between these variables within college students. Study 2 adopted a longitudinal approach, surveying 905 college students across three-time points. This study was designed to explore the temporal mediation of general life satisfaction in the gratitude-patriotism relationship, offering insights into the evolution of these constructs over time. The sequential surveys aimed to capture the dynamic nature of gratitude's impact on patriotism, considering the continuous interplay with general life satisfaction among college students. Results: Study 1 reveals a noteworthy finding: Gratitude enables the direct prediction of patriotism, while additionally, general life satisfaction plays a role between them. Furthermore, the predictive effect of gratitude on patriotism is strengthened among individuals with higher levels of socioeconomic status. However, there is no significant moderating effect between general life satisfaction and patriotism by socioeconomic status. Study 2 demonstrates that general life satisfaction plays a significant mediating role in the relationship between gratitude and patriotism, over a period of three times. However, the moderating influence of socioeconomic status was not substantiated in the longitudinal mediation model. Conclusion: These two studies shed light on the complex relationship between gratitude and patriotism. They emphasize the significance of gratitude, general life satisfaction, and socioeconomic status in shaping patriotism, offering potential avenues for understanding the internal mechanisms that influence patriotism.
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In China, certain Monascus ruber strains are traditionally used as edible fungi. We sequenced the genome of M. ruber FM39-7 strain, an isolate from fermented rice. The genome is 25.89 Mb with a G + C content of 48.86%, containing 8485 annotated genes.
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Rapid and cost-efficient antibiotic susceptibility testing (AST) is key to timely prescription-oriented diagnosis and precision treatment. However, current AST methods have limitations in throughput or cost effectiveness, and are impractical for microbial communities. Here, we developed a high-throughput micro-well array-based colorimetric AST (macAST) system equipped with a self-developed smartphone application that could efficiently test sixteen combinations of bacteria strains and antibiotics, achieving comparable AST results based on resazurin metabolism assay. For community samples, we integrated immunomagnetic separation into the macAST (imacAST) system to specifically enrich the target cells before testing, which shortened bacterial isolation time from days to only 45 min and achieved AST of the target bacteria with a low concentration (~103 CFU/mL). This proof-of-concept study developed a high-throughput AST system with an at least ten-fold reduction in cost compared with a system equipped with a microscope or Raman spectrum. Based on colorimetric readout, the antimicrobial susceptibility of the bacteria from microbial communities can be delivered within 6 h, compared to days being required based on standard procedures, bypassing the need for precise instrumentation in therapy to combat bacterial antibiotic resistance in resource-limited settings.
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Antibacterianos , Colorimetria , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Bactérias , Farmacorresistência BacterianaRESUMO
BACKGROUND: The vitamin D level in the blood is associated with the incidence of hypertension. The present study investigated whether or not calcitriol, an active form of vitamin D, reverses age-related hypertension. METHODS: Young (3-month-old) and aged (12-month-old) C57BL/6 male mice were administered with or without calcitriol at 150 ng/kg per day by oral gavage for 8 weeks. Blood pressure was measured by tail-cuff plethysmography and telemetry, and superoxide production in renal tissue was assessed by fluorescence imaging, and the protein expression of AP1/AT1R signaling pathway was examined by Western blot. RESULTS: We showed that 24-hour renal sodium excretion was impaired and blood pressure was increased in aged mice, which was related to the enhancement of renal AT1R expression and function. In addition, the expression of transcription factor AP1 (a dimer of c-Fos and c-Jun) and the binding of AP1 to the AT1R promoter region was significantly enhanced, accompanied by decreased nuclear translocation of Nrf2, abnormal mitochondrial function including decreased ATP production, NAD+/NADH ratio and mtDNA copy numbers, and increased reactive oxygen species. Calcitriol increased 24-hour urinary sodium excretion and reduced blood pressure in aged mice. Mechanically, calcitriol increased the nuclear translocation of Nrf2, improved mitochondrial function, reduced AP1 binding ability to AT1R promoter, which reversed enhanced AT1R expression and function, and lowered blood pressure in aged mice. CONCLUSIONS: Our findings indicated that calcitriol reversed age-related hypertension via downregulating renal AP1/AT1R pathway through regulating mitochondrial function. Thus, calcitriol may be a valuable therapeutic strategy for age-related hypertension.
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Calcitriol , Hipertensão , Masculino , Camundongos , Animais , Calcitriol/farmacologia , Fator 2 Relacionado a NF-E2 , Receptor Tipo 1 de Angiotensina/metabolismo , Camundongos Endogâmicos C57BL , Hipertensão/metabolismo , Pressão Sanguínea/fisiologia , Mitocôndrias/metabolismo , SódioRESUMO
Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic ß cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
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Diabetes Mellitus Tipo 2 , Morus , Camundongos , Animais , Tecido Adiposo Marrom , Sirtuína 1/genética , Sirtuína 1/metabolismo , Sirtuína 1/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Morus/metabolismo , Flavonoides/farmacologia , Flavonoides/metabolismo , Estudos Prospectivos , Transdução de Sinais , Tecido Adiposo Branco , Folhas de Planta , Proteína Desacopladora 1/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismoRESUMO
Cancer microenvironment plays an important role in the proliferation and metastasis of hepatocarcinoma cancer cells (HCC). Exosomes from bone marrow-derived mesenchymal stem cells (BMSCs) are a component of the cancer microenvironment. In this study, we reveal that miRNA-652-3P from BMSC-derived exosomes promotes proliferation and metastasis in HCC. The ability of cancer proliferation, migration and invasion can be evaluated after co-culture by CCK-8, wound healing and transwell assay. Isolated exosomes were identified by transmission electron microscopy (TEM) and the biomarkers of the purified exosomes were showed in West-blotting (WB). MiR-652-3p was detected in the HepG2 and 7721 after co-culturing with exosome derived from BMSCs under different conditions. Target authentication was performed by a luciferase reporter assay to confirm the presumptive target of miR-652-3p. After overexpressing miR-652-3p, the mRNA and protein expression level of TNRC6A in HCC was examined by q-PCR and WB. Further, we observed greater miR-652-3p upregulation in hypoxic BMSCs-exosomes than in normal- exosomes. In addition, a miR-652-3p inhibitor attenuates the proliferation and metastasis of HCC cells after co-culturing with BMSCs. Our data demonstrate that hypoxic BMSCs-derived exosomal miR-652-3p promotes proliferation in HCC cells by inhibiting TNRC6A. The BMSCs-derived exosomal miR-652-3p may help find patient-targeted therapies in hepatocarcinoma cancer.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Proliferação de Células/genética , Hipóxia , Neoplasias Hepáticas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Microambiente Tumoral/genéticaRESUMO
INTRODUCTION: The turnover and shortage of health care workers (HCWs) have been a worldwide problem for healthcare organizations. The primary aim of this study was to identify the factors influencing the intention of Chinese HCWs to leave their job, especially meaning in life and professional happiness. METHODS: This observational cross-sectional study, conducted among 1125 full-time HCWs, assessed demographic variables, meaning in life, professional happiness, and turnover intention by a survey. The survey was distributed to HCWs in three tertiary hospitals. The data were analyzed by T-tests, ANOVA, Kruskal-Wallis tests and hierarchical linear regression model. RESULTS: There were statistically significant differences in turnover intention of HCWs by gender, age, role, educational level, years in practice, and number of monthly night shifts. HCWs' meaning in life and professional happiness were negatively associated with the turnover intention. Furthermore, after controlling for other factors, meaning in life explained 3.7% of the turnover intention and professional happiness explained 13.4%. CONCLUSION: In our study, positive psychological factors were related to turnover intentions. Professional happiness was the strongest predictor. Thus, health human resource managers should foster positive psychology among HCWs to reduce their turnover.
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Esgotamento Profissional , Intenção , Humanos , Estudos Transversais , Felicidade , Esgotamento Profissional/psicologia , Satisfação no Emprego , Pessoal de Saúde/psicologia , Reorganização de Recursos Humanos , China , Inquéritos e QuestionáriosRESUMO
Tilmicosin is a semi-synthetic macrolide for veterinary use with strong antibacterial effect on respiratory bacteria. In this study, the pharmacokinetic/pharmacodynamic (PK/PD) integration of tilmicosin against Pasteurella multocida (P. multocida) was evaluated by establishing a piglet tissue cage infection model. Concentration of tilmicosin and bacterial numbers of P. multocida in the tissue-cage fluid were monitered. After the population of P. multocida was equal to or greater than 107 CFU/mL in a tissue cage, piglets received an oral administration of tilmicosin at a dose of 30, 40, 50, and 60 mg/kg b.w., once daily for 3 days, respectively. Bacteria were counted every 24 h after drug administration and at 48 and 72 h after the last administration. A sigmoidal Emax model was used to fit the relationship between PK/PD parameters and the antibacterial effect. AUC24h/MIC was the best PK/PD index that correlated with effectiveness of tilmicosin against P. multocida. The magnitude of AUC24h/MIC required for continuous 1/3-log, 1/2-log, and 3/4-log reductions were 19.65 h, 23.86 h, and 35.77 h, respectively, during each 24 h treatment period. In this study, when the dosage was >50 mg/kg, the AUC24h/MIC was still >35.77 h in the period of 24-48 h after the last administration due to the slow elimination, that is, tilmicosin exhibited a potent antibacterial effect against P. multocida after three successive daily administrations. The data provide meaningful guidance to optimize regimens of tilmicosin to treat respiratory tract infections caused by P. multocida.