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Type 2 diabetes (T2D) is potentially linked to disordered tryptophan metabolism that attributes to the intricate interplay among diet, gut microbiota, and host physiology. However, underlying mechanisms are substantially unknown. Comparing the gut microbiome and metabolome differences in mice fed a normal diet (ND) and high-fat diet (HFD), we uncover that the gut microbiota-dependent tryptophan metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) is present at lower concentrations in mice with versus without insulin resistance. We further demonstrate that the microbial transformation of tryptophan into 5-HIAA is mediated by Burkholderia spp. Additionally, we show that the administration of 5-HIAA improves glucose intolerance and obesity in HFD-fed mice, while preserving hepatic insulin sensitivity. Mechanistically, 5-HIAA promotes hepatic insulin signaling by directly activating AhR, which stimulates TSC2 transcription and thus inhibits mTORC1 signaling. Moreover, T2D patients exhibit decreased fecal levels of 5-HIAA. Our findings identify a noncanonical pathway of microbially producing 5-HIAA from tryptophan and indicate that 5-HIAA might alleviate the pathogenesis of T2D.
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Dieta Hiperlipídica , Microbioma Gastrointestinal , Resistência à Insulina , Fígado , Alvo Mecanístico do Complexo 1 de Rapamicina , Receptores de Hidrocarboneto Arílico , Transdução de Sinais , Triptofano , Proteína 2 do Complexo Esclerose Tuberosa , Animais , Dieta Hiperlipídica/efeitos adversos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Triptofano/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Receptores de Hidrocarboneto Arílico/metabolismo , Fígado/metabolismo , Humanos , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/microbiologia , Fatores de Transcrição Hélice-Alça-Hélice BásicosRESUMO
BACKGROUND: Phosphorus plays a key role in plant adaptation to adversity and plays a positive role in the yield and quality formation of apples. Genes of the SPX domain-containing family are widely involved in the regulation of phosphorus signalling networks. However, the mechanisms controlling phosphorus deficiency are not completely understood in self-rooted apple stock. RESULTS: In this study, 26 members of the apple SPX gene family were identified by genome-wide analysis, and further divided into four subfamilies (SPX, SPX-MFS, SPX-EXS, and SPX-RING) based on their structural features. The chromosome distribution and gene duplications of MdSPXs were also examined. The promoter regions of MdSPXs were enriched for multiple biotic/abiotic stresses, hormone responses and typical P1BS-related elements. Analysis of the expression levels of 26 MdSPXs showed that some members were remarkably induced when subjected to low phosphate (Pi) stress, and in particular MdSPX2, MdSPX3, and MdPHO1.5 exhibited an intense response to low Pi stress. MdSPX2 and MdSPX3 showed significantly divergent expression levels in low Pi sensitive and insensitive apple species. Protein interaction networks were predicted for 26 MdSPX proteins. The interaction of MdPHR1 with MdSPX2, MdSPX3, MdSPX4, and MdSPX6 was demonstrated by yeast two-hybrid assay, suggesting that these proteins might be involved in the Pi-signaling pathway by interacting with MdPHR1. CONCLUSION: This research improved the understanding of the apple SPX gene family and contribute to future biological studies of MdSPX genes in self-rooted apple stock.
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Evolução Molecular , Malus , Família Multigênica , Fósforo , Proteínas de Plantas , Estresse Fisiológico , Malus/genética , Malus/metabolismo , Estresse Fisiológico/genética , Fósforo/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Filogenia , Regiões Promotoras Genéticas , Duplicação Gênica , Mapas de Interação de ProteínasRESUMO
BACKGROUND: Proteins harboring the SPX domain are crucial for the regulation of phosphate (Pi) homeostasis in plants. This study aimed to identify and analyze the entire SPX gene family within the cucumber genome. RESULTS: The cucumber genome encompassed 16 SPX domain-containing genes, which were distributed across six chromosomes and categorized into four distinct subfamilies: SPX, SPX-MFS, SPX-EXS and SPX-RING, based on their structure characteristics. Additionally, gene duplications and synteny analysis were conducted for CsSPXs, revealing that their promoter regions were enriched with a variety of hormone-responsive, biotic/abiotic stress and typical P1BS-related elements. Tissue expression profiling of CsSPX genes revealed that certain members were specifically expressed in particular organs, suggesting essential roles in cucumber growth and development. Under low Pi stress, CsSPX1 and CsSPX2 exhibited a particularly strong response to Pi starvation. It was observed that the cucumber cultivar Xintaimici displayed greater tolerance to low Pi compared to black-spined cucumber under low Pi stress conditions. Protein interaction networks for the 16 CsSPX proteins were predicted, and yeast two-hybrid assay revealed that CsPHR1 interacted with CsSPX2, CsSPX3, CsSPX4 and CsSPX5, implying their involvement in the Pi signaling pathway in conjunction with CsPHR1. CONCLUSION: This research lays the foundation for further exploration of the function of the CsSPX genes in response to low Pi stress and for elucidating the underlying mechanism.
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Cucumis sativus , Família Multigênica , Fósforo , Proteínas de Plantas , Cucumis sativus/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fósforo/metabolismo , Fósforo/deficiência , Genoma de Planta , Genes de Plantas , Regulação da Expressão Gênica de Plantas , FilogeniaRESUMO
Chemodynamic therapy (CDT) is a non-invasive strategy for generating reactive oxygen species (ROS) and is promising for cancer treatment. However, increasing ROS in tumor therapy remains challenging. Therefore, exogenous excitation and inhibition of electron-hole pair recombination are attractive for modulating ROS storms in tumors. Herein, a Ce-doped BiFeO3 (CBFO) piezoelectric sonosensitizer to modulate ROS generation and realize a synergistic mechanism of CDT/sonodynamic therapy and piezodynamic therapy (PzDT) is proposed. The mixed Fe2+ and Ce3+ can implement a circular Fenton/Fenton-like reaction in the tumor microenvironment. Abundant ·OH can be generated by ultrasound (US) stimulation to enhance CDT efficacy. As a typical piezoelectric sonosensitizer, CBFO can produce O2 - owing to the enhanced polarization by the US, resulting in the motion of charge carriers. In addition, CBFO can produce a piezoresponse irradiated upon US, which accelerates the migration rate of electrons/holes in opposite directions and results in energy band bending, further achieving toxic ROS production and realizing PzDT. Density functional theory calculations confirmed that Ce doping shortens the diffusion of electrons and improves the conductivity and catalytic activity of CBFO. This distinct US-enhanced strategy emphasizes the effects of doping engineering and piezoelectric-optimized therapy and shows great potential for the treatment of malignant tumors.
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Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder characterized by left ventricular hypertrophy. Sudden cardiac death (SCD) is a rare but the most catastrophic complication in patients with HCM. Implantable cardioverter-defibrillators (ICDs) are widely recognized as effective preventive measures for SCD. Individualized risk stratification and early intervention in HCM can significantly improve patient prognosis. In this study, we review the latest findings regarding pathogenesis, risk stratification, and prevention of SCD in HCM patients, highlighting the clinic practice of cardiovascular magnetic resonance imaging for SCD management.
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Cardiomiopatia Hipertrófica , Desfibriladores Implantáveis , Humanos , Fatores de Risco , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/terapia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Coração , Desfibriladores Implantáveis/efeitos adversos , Medição de RiscoRESUMO
Nonlinear sum frequency generation (SFG) and difference frequency generation (DFG) are fundamental methods to obtain new light sources for various applications. However, most of the on-chip SFG and DFG are based on conventional resonators, lacking robustness against fabrication defects. Here, we demonstrate topologically protected SFG and DFG in a second-order topological photonic system. The mechanism is based on the nonlinear interaction between three high-Q corner modes inside dual topological band gaps. The frequency matching condition for SFG and DFG is precisely satisfied by designing a valley-photonic-crystal-like topological system, which provides more freedoms to tune the corner modes. The topological SFG and DFG are achieved with high conversion efficiency, and the underlying topological physics is revealed. This work opens up avenues toward topologically protected nonlinear frequency conversion, and can find applications in the fields of on-chip single-photon detections and optical quantum memories with robustness against defects.
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Adaptive human learning utilizes reward prediction errors (RPEs) that scale the differences between expected and actual outcomes to optimize future choices. Depression has been linked with biased RPE signaling and an exaggerated impact of negative outcomes on learning which may promote amotivation and anhedonia. The present proof-of-concept study combined computational modeling and multivariate decoding with neuroimaging to determine the influence of the selective competitive angiotensin II type 1 receptor antagonist losartan on learning from positive or negative outcomes and the underlying neural mechanisms in healthy humans. In a double-blind, between-subjects, placebo-controlled pharmaco-fMRI experiment, 61 healthy male participants (losartan, n = 30; placebo, n = 31) underwent a probabilistic selection reinforcement learning task incorporating a learning and transfer phase. Losartan improved choice accuracy for the hardest stimulus pair via increasing expected value sensitivity towards the rewarding stimulus relative to the placebo group during learning. Computational modeling revealed that losartan reduced the learning rate for negative outcomes and increased exploitatory choice behaviors while preserving learning for positive outcomes. These behavioral patterns were paralleled on the neural level by increased RPE signaling in orbitofrontal-striatal regions and enhanced positive outcome representations in the ventral striatum (VS) following losartan. In the transfer phase, losartan accelerated response times and enhanced VS functional connectivity with left dorsolateral prefrontal cortex when approaching maximum rewards. These findings elucidate the potential of losartan to reduce the impact of negative outcomes during learning and subsequently facilitate motivational approach towards maximum rewards in the transfer of learning. This may indicate a promising therapeutic mechanism to normalize distorted reward learning and fronto-striatal functioning in depression.
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Angiotensinas , Estriado Ventral , Humanos , Masculino , Losartan/farmacologia , Recompensa , Comunicação , Imageamento por Ressonância MagnéticaRESUMO
Molting is a crucial biological process of crustaceans. Crustaceans go through three separate stages throughout their molting process, including pre-molt, post-molt and inter-molt. However, the exact mechanism of immunological modulation during molting remains unclear. Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been extensively documented to participate in immune defense. In the present study, a TRAF6 gene with two TRAF-type zinc finger domains was identified from Eriocheir sinensis (designed as EsTRAF6), and its role in regulating immune response during molting process was explored. The mRNA expression level of EsTRAF6 at pre-molt stage was higher than that at post-molt stage and inter-molt stage. After Aeromonas hydrophila stimulation, the expression levels of EsTRAF6, EsRelish and anti-lipopolysaccharide factors (ALFs) genes exhibited a considerable increase at three molting stages. Subsequently, the expression patterns of EsTRAF6 and EsRelish in response to the treatment with 20-hydroxyecdysone (20E) were examined. The mRNA expression of EsTRAF6 and EsRelish were significantly increased at 12 h after 20E injection. Additionally, the protein expression level of TRAF6 was also up-regulated in 20E group compared to control group. Furthermore, the role of EsTRAF6 in regulating the anti- ALFs expression at pre-molt stage post A. hydrophila stimulation was investigated. Following the inhibition of the EsTRAF6 transcript using RNAi or the injection of inhibitor (TMBPS), there was a notable decrease of the EsALF1, EsALF2 and EsALF3 transcripts. Moreover, a significant reduction in the phosphorylation level of NF-κB at pre-molt stage was observed after A. hydrophila stimulation in TRAF6-inhibited crabs. Collectively, our results suggest that EsTRAF6 could be induced by 20E and promoted the EsALFs expression by activating NF-κB at pre-molt stage, which provides a novel insight into the research of immune regulatory mechanism during the process of molting of crustaceans.
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BACKGROUND: Pulmonary emphysema is a condition that causes damage to the lung tissue over time. GBP5, as part of the guanylate-binding protein family, is dysregulated in mouse pulmonary emphysema. However, the role of GBP5 in lung inflammation in ARDS remains unveiled. METHODS: To investigate whether GBP5 regulates lung inflammation and autophagy regulation, the study employed a mouse ARDS model and MLE-12 cell culture. Vector transfection was performed for the genetic manipulation of GBP5. Then, RT-qPCR, WB and IHC staining were conducted to assess its transcriptional and expression levels. Histological features of the lung tissue were observed through HE staining. Moreover, ELISA was conducted to evaluate the secretion of inflammatory cytokines, autophagy was assessed by immunofluorescent staining, and MPO activity was determined using a commercial kit. RESULTS: Our study revealed that GBP5 expression was altered in mouse ARDS and LPS-induced MLE-12 cell models. Moreover, the suppression of GBP5 reduced lung inflammation induced by LPS in mice. Conversely, overexpression of GBP5 diminished the inhibitory impact of LPS on ARDS during autophagy, leading to increased inflammation. In the cell line of MLE-12, GBP5 exacerbates LPS-induced inflammation by blocking autophagy. CONCLUSION: The study suggests that GBP5 facilitates lung inflammation and autophagy regulation. Thus, GBP5 could be a potential therapeutic approach for improving ARDS treatment outcomes, but further research is required to validate these findings.
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Autofagia , Proteínas de Ligação ao GTP , Lesão Pulmonar , Pneumonia , Síndrome do Desconforto Respiratório , Animais , Camundongos , Autofagia/efeitos dos fármacos , Inflamação/metabolismo , Lipopolissacarídeos , Pulmão/metabolismo , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/metabolismo , Pneumonia/metabolismo , Enfisema Pulmonar , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/metabolismo , Proteínas de Ligação ao GTP/antagonistas & inibidores , Proteínas de Ligação ao GTP/metabolismoRESUMO
Aspartyl dipeptidase (dipeptidase E) can hydrolyze Asp-X dipeptides (where X is any amino acid), and the enzyme plays a key role in the degradation of peptides as nutrient sources. Dipeptidase E remains uncharacterized in Streptomyces. Orf2 from Streptomyces sp. 139 is located in the exopolysaccharide biosynthesis gene cluster, which may be a novel dipeptidase E with "S134-H170-D198" catalytic triad by sequence and structure comparison. Herein, recombinant Orf2 was expressed in E. coli and characterized dipeptidase E activity using the Asp-ρNA substrate. The optimal pH and temperature for Orf2 are 7.5 and 40 â; Vmax and Km of Orf2 are 0.0787 mM·min-1 and 1.709 mM, respectively. Orf2 exhibits significant degradation activities to Asp-Gly-Gly, Asp-Leu, Asp-His, and isoAsp-Leu and minimal activities to Asp-Pro and Asp-Ala. Orf2 contains a Ser-His-Asp catalytic triad characterized by point mutation. In addition, the Asp147 residue of Orf2 is also proven to be critical for the enzyme's activity through molecular docking and point mutation. Transcriptome analysis reveals the upregulation of genes associated with ribosomes, amino acid biosynthesis, and aminoacyl-tRNA biosynthesis in the orf2 mutant strain. Compared with the orf2 mutant strain and WT, the yield of crude polysaccharide does not change significantly. However, crude polysaccharides from the orf2 mutant strain exhibit a wider range of molecular weight distribution. The results indicate that the Orf2 links nutrient stress to secondary metabolism as a novel dipeptidase E. KEY POINTS: ⢠A novel dipeptidase E with a Ser-His-Asp catalytic triad was characterized from Streptomyces sp. 139. ⢠Orf2 was involved in peptide metabolism both in vitro and in vivo. ⢠Orf2 linked nutrient stress to mycelia formation and secondary metabolism in Streptomyces.
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Dipeptidases , Streptomyces , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Dipeptidases/metabolismo , Dipeptidases/genética , Dipeptidases/química , Dipeptídeos/metabolismo , Concentração de Íons de Hidrogênio , Cinética , Simulação de Acoplamento Molecular , Família Multigênica , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/química , Streptomyces/genética , Streptomyces/enzimologia , Especificidade por Substrato , TemperaturaRESUMO
BACKGROUND: Mycoplasma pneumoniae (MP) is one of the most common causes of community-acquired pneumonia in children. Most children have fever. In 2021, we found that the proportion of children without fever increased. The aim of this study is to summarize the differences in the clinical characteristics of children with MP pneumonia who are febrile or not, and to raise awareness of children who are not febrile. METHOD: Demographic information of the children was collected on admission. Clinical manifestations during the course of the disease and the first laboratory, imaging, and pulmonary function tests before discharge were recorded and compared. RESULTS: From August to December, a total of 542 people were included in the study. We found that older children were more likely to have fever. Inflammatory indicators including procalcitonin (P = 0.030), C-reaction protein (P < 0.001), erythrocyte sedimentation rate (P < 0.001), ferritin (P = 0.040) and the rate of atelectasis (P = 0.049) of febrile children were higher in febrile children. However, the elevated lactate dehydrogenase and pulmonary function impairment (P all > 0.05), especially the small airway function impairment, are no lower in afebrile children than in febrile children. CONCLUSION: The fever rate is lower in younger children, but wheezing is more common. In afebrile children, the impairment of organ and lung function was no less than in febrile children. Therefore, attention should also be paid to children who are not febrile.
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Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Criança , Humanos , Adolescente , Pneumonia por Mycoplasma/complicações , Pneumonia por Mycoplasma/diagnóstico , Pulmão , Proteína C-Reativa , Febre/etiologia , Estudos RetrospectivosRESUMO
Tool wear prediction is of great significance in industrial production. Current tool wear prediction methods mainly rely on the indirect estimation of machine learning, which focuses more on estimating the current tool wear state and lacks effective quantification of random uncertainty factors. To overcome these shortcomings, this paper proposes a novel method for predicting cutting tool wear. In the offline phase, the multiple degradation features were modeled using the Brownian motion stochastic process and a SVR model was trained for mapping the features and the tool wear values. In the online phase, the Bayesian inference was used to update the random parameters of the feature degradation model, and the future trend of the features was estimated using simulation samples. The estimation results were input into the SVR model to achieve in-advance prediction of the cutting tool wear in the form of distribution densities. An experimental tool wear dataset was used to verify the effectiveness of the proposed method. The results demonstrate that the method shows superiority in prediction accuracy and stability.
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Ultrafast interfacing of electrical and optical signals at the nanoscale is highly desired for on-chip applications including optical interconnects and data processing devices. Here, we report electrically driven nanoscale optical sources based on metal-insulator-graphene tunnel junctions (MIG-TJs), featuring waveguided output with broadband spectral characteristics. Electrically driven inelastic tunneling in a MIG-TJ, realized by integrating a silver nanowire with graphene, provides broadband excitation of plasmonic modes in the junction with propagation lengths of several micrometers (â¼10 times larger than that for metal-insulator-metal junctions), which therefore propagate toward the junction edge with low loss and couple to the nanowire waveguide with an efficiency of â¼70% (â¼1000 times higher than that for metal-insulator-metal junctions). Alternatively, lateral coupling of the MIG-TJ to a semiconductor nanowire provides a platform for efficient outcoupling of electrically driven plasmonic signals to low-loss photonic waveguides, showing potential for applications at various integration levels.
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Dementia exists as a 'progressive clinical syndrome of deteriorating mental function significant enough to interfere with activities of daily living', with the most prevalent type of dementia being Alzheimer's disease (AD), accounting for about 80% of diagnosed cases. AD is associated with an increased risk of comorbidity with other clinical conditions such as hypertension, diabetes, and neuropsychiatric symptoms (NPS) including, agitation, anxiety, and depression as well as increased mortality in late life. For example, up to 70% of patients diagnosed with AD are affected by anxiety. As aging is the major risk factor for AD, this represents a huge global burden in ageing populations. Over the last 10 years, significant efforts have been made to recognize the complexity of AD and understand the aetiology and pathophysiology of the disease as well as biomarkers for early detection. Yet, earlier treatment options, including acetylcholinesterase inhibitors and glutamate receptor regulators, have been limited as they work by targeting the symptoms, with only the more recent FDA-approved drugs being designed to target amyloid-ß protein with the aim of slowing down the progression of the disease. However, these drugs may only help temporarily, cannot stop or reverse the disease, and do not act by reducing NPS associated with AD. The first-line treatment options for the management of NPS are selective serotonin reuptake inhibitors/selective noradrenaline reuptake inhibitors (SSRIs/SNRIs) targeting the monoaminergic system; however, they are not rational drug choices for the management of anxiety disorders since the GABAergic system has a prominent role in their development. Considering the overall treatment failures and side effects of currently available medication, there is an unmet clinical need for rationally designed therapies for anxiety disorders associated with AD. In this review, we summarize the current status of the therapy of AD and aim to highlight novel angles for future drug therapy in our ongoing efforts to alleviate the cognitive deficits and NPS associated with this devastating disease.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/etiologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Animais , Inibidores da Colinesterase/uso terapêuticoRESUMO
One previously undescribed alkaloid, named penifuranone A (1), and three known compounds (2-4) were isolated from the mangrove endophytic fungus Penicillium crustosum SCNU-F0006. The structure of the new alkaloid (1) was elucidated based on extensive spectroscopic data analysis and single-crystal X-ray diffraction analysis. Four natural isolates and one new synthetic derivative of penifuranone A, compound 1a, were screened for their antimicrobial, antioxidant, and anti-inflammatory activities. Bioassays revealed that penifuranone A (1) exhibited strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 42.2 µM. The docking study revealed that compound 1 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.
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Alcaloides , Óxido Nítrico , Penicillium , Penicillium/química , Penicillium/metabolismo , Camundongos , Animais , Alcaloides/química , Alcaloides/farmacologia , Alcaloides/isolamento & purificação , Células RAW 264.7 , Óxido Nítrico/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Óxido Nítrico Sintase Tipo II/metabolismo , Simulação de Acoplamento Molecular , Lipopolissacarídeos , Antioxidantes/farmacologia , Antioxidantes/química , Estrutura MolecularRESUMO
BACKGROUND: Education has been recognised as necessary in forming and internalising professional values. The system and instructors' content in existing educational institutions focus on developing students' knowledge, skills and practices. Still, the development of values has yet to achieve significant effects, leading to a crisis in students' professional identity. AIMS: To construct a professional values growth theory for undergraduate nursing students and develop a corresponding education framework. METHODS: Through the review, some databases(PubMedãCINAHLãWeb of ScienceãWiley and Google Scholars)were searched using a systematic search strategy to collect relevant literature on professional values education. Based on the nursing professional values growth theory (Li and Li, Nursing Ethics In press, 2022), a theory of professional values growth of nursing undergraduates was developed using the method of theory derivation. Two rounds of expert meetings were conducted to review and revise an education framework of professional values of nursing undergraduates derived from that theory. FINDINGS: A total of 10 studies were included. The contents of two themes were analysed: theories and models and the current status of the professional values development of nursing students. The resulting professional values growth theory for undergraduate nursing students consists of five parts: key aspects, decisive opportunities, drivers, embodiment (humanistic sentiments, moral emotions), and outcomes. A total of five experts in the relevant fields were invited to this study. After two rounds of expert meetings, an education framework for undergraduate nursing students was finally developed, which consists of four parts: education objectives, education process and content, environment and conditions, and evaluation. CONCLUSION: The education framework developed in this study has practical implications for the development of professional values of undergraduate nursing students, providing educational strategies and methods for the growth and internalisation of professional values of undergraduate nursing students.
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BACKGROUND: The formation of nursing professional values is crucial to the development of the nursing profession, but it is influenced by various factors. The process of shaping nursing professional values in different growth contexts has been overlooked. In order to establish professional values in the context of Chinese nursing, it is necessary to investigate the evolution of nursing professional values throughout history. PURPOSE: To develop a theory of professional values growth from a nursing context. Design: This study adopted a grounded theory approach from Strauss and Corbin. PARTICIPANTS: From November 2021 to March 2022, a total of 33 participants were included. METHODS: Data were collected using a semi-structured interview over telephone or online or face to face and were analysed using open, axial, and selective coding, with the help of MAXQDA 2020. ETHICAL CONSIDERATIONS: The research was approved by the Ethics Committee of the China Medical University. All participants signed the informed consent and agreed to be interviewed before the study. FINDINGS: The study has developed a theoretical construct of nursing professional values growth that consists of five dimensions: key aspects, decisive opportunities, drivers, embodiment, and shaping outcomes. And key aspects include four subcategories (the initial stage, the consciousness stage, the core stage, and the action stage). Decisive opportunities come from organisations and individuals. Drivers consist of social culture and self-trait, and embodiment covers two subcategories (humanism and ethical emotions). The last dimension is shaping outcomes, which consists of three subcategories (maintaining the original intention, professionalism, and instilling professional values). DISCUSSION: The theory demonstrates the individual development process of nursing professional values in different interactive contexts, the context of its interaction with social and personal values is revealed, and the dynamics and mechanisms of the formation of personal psychological qualities in professional values from a nursing context are discovered. CONCLUSIONS: This theory reveals the mechanisms that shape nursing professional values and can provide guidance for the growth of nursing students' professional values.
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The presence of human immunodeficiency virus (HIV) 1 subtype A6, characterized by the L74I integrase (IN) polymorphism, is associated with confirmed virologic failure in clinical trials of long-acting cabotegravir and rilpivirine. We investigated the effect of L74I on replication capacity (RC) of recombinant viruses carrying this polymorphism in combination with various IN stand-transfer inhibitor resistance mutations. The presence of L74I conferred greater RC to recombinant viruses expressing HIV-1 A6 IN when present together with G118R, G140R, Q148H, and R263K; no significant difference in RC was observed for the Q148K or R mutants. These findings may explain, in part, the association of HIV-1 subtype A6 with virologic failure.
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Infecções por HIV , Inibidores de Integrase de HIV , Integrase de HIV , HIV-1 , Humanos , HIV-1/genética , Substituição de Aminoácidos , Replicação Viral/genética , Oxazinas/uso terapêutico , Inibidores de Integrase de HIV/farmacologia , Inibidores de Integrase de HIV/uso terapêutico , Mutação , Piridonas/farmacologia , Piridonas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Farmacorresistência Viral/genética , Integrase de HIV/genéticaRESUMO
BACKGROUND: The genus Zingiber of the Zingiberaceae is distributed in tropical, subtropical, and in Far East Asia. This genus contains about 100-150 species, with many species valued as important agricultural, medicinal and horticultural resources. However, genomic resources and suitable molecular markers for species identification are currently sparse. RESULTS: We conducted comparative genomics and phylogenetic analyses on Zingiber species. The Zingiber chloroplast genome (size range 162,507-163,711 bp) possess typical quadripartite structures that consist of a large single copy (LSC, 86,986-88,200 bp), a small single copy (SSC, 15,498-15,891 bp) and a pair of inverted repeats (IRs, 29,765-29,934 bp). The genomes contain 113 unique genes, including 79 protein coding genes, 30 tRNA and 4 rRNA genes. The genome structures, gene contents, amino acid frequencies, codon usage patterns, RNA editing sites, simple sequence repeats and long repeats are conservative in the genomes of Zingiber. The analysis of sequence divergence indicates that the following genes undergo positive selection (ccsA, ndhA, ndhB, petD, psbA, psbB, psbC, rbcL, rpl12, rpl20, rpl23, rpl33, rpoC2, rps7, rps12 and ycf3). Eight highly variable regions are identified including seven intergenic regions (petA-pabJ, rbcL-accD, rpl32-trnL-UAG, rps16-trnQ-UUG, trnC-GCA-psbM, psbC-trnS-UGA and ndhF-rpl32) and one genic regions (ycf1). The phylogenetic analysis revealed that the sect. Zingiber was sister to sect. Cryptanthium rather than sect. Pleuranthesis. CONCLUSIONS: This study reports 14 complete chloroplast genomes of Zingiber species. Overall, this study provided a solid backbone phylogeny of Zingiber. The polymorphisms we have uncovered in the sequencing of the genome offer a rare possibility (for Zingiber) of the generation of DNA markers. These results provide a foundation for future studies that seek to understand the molecular evolutionary dynamics or individual population variation in the genus Zingiber.
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Genoma de Cloroplastos , Zingiberaceae , Filogenia , Zingiberaceae/genética , Genômica/métodos , Polimorfismo Genético , Evolução MolecularRESUMO
Fabricating polymer electrolyte membranes (PEMs) simultaneously with high ion conductivity and selectivity has always been an ultimate goal in many membrane-integrated systems for energy conversion and storage. Constructing broader ion-conducting channels usually enables high-efficient ion conductivity while often bringing increased crossover of other ions or molecules simultaneously, resulting in decreased selectivity. Here, the ultra-small carbon dots (CDs) with the selective barriers are self-assembled within proton-conducting channels of PEMs through electrostatic interaction to enhance the proton conductivity and selectivity simultaneously. The functional CDs regulate the nanophase separation of PEMs and optimize the hydration proton network enabling higher-efficient proton transport. Meanwhile, the CDs within proton-conducting channels prevent fuel from permeating selectively due to their repelling and spatial hindrance against fuel molecules, resulting in highly enhanced selectivity. Benefiting from the improved conductivity and selectivity, the open-circuit voltage and maximum power density of the direct methanol fuel cell (DMFC) equipped with the hybrid membranes raised by 23% and 93%, respectively. This work brings new insight to optimize polymer membranes for efficient and selective transport of ions or small molecules, solving the trade-off of conductivity and selectivity.