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The objective of the study was to explore the association between basic vital signs and consciousness status in patients with primary brainstem hemorrhage (PBH). Patients with PBH were categorized into two groups based on Glasgow Coma Scale (GCS) scores: disturbance of consciousness (DOC) group (GCS=3-8) and non-DOC group (GCS=15). Within DOC group, patients were further divided into behavioral (GCS=4-8) and non-behavioral (GCS=3) subgroups. Basic vital signs, such as body temperature, heart rate, and respiratory rate, were monitored every 3 hours during the acute bleeding phase (1st day) and the bleeding stable phase (7th day) of hospitalization. The findings revealed a negative correlation between body temperature and heart rate with GCS scores in DOC group at both time points. Moreover, basic vital signs were notably higher in the DOC group compared to non-DOC group. Specifically, the non-behavioral subgroup within DOC group exhibited significantly elevated heart rates on the 1st day of hospitalization and moderately increased respiratory rates on the 7th day compared to the control group. Scatter plots illustrated a significant relationship between body temperature and heart rate with consciousness status, while no significant correlation was observed with respiratory rate. In conclusion, the study suggests that monitoring basic vital signs, particularly body temperature and heart rate, can serve as valuable indicators for evaluating consciousness status in PBH patients. These basic vital signs demonstrated variations corresponding to lower GCS scores. Furthermore, integrating basic vital sign monitoring with behavioral assessment could enhance the assessment of consciousness status in PBH patients.
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BACKGROUND: Owing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship. METHODS: Firstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation. RESULTS: The increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation. CONCLUSIONS: Our work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.
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Tecido Adiposo , Modelos Animais de Doenças , Receptor do Peptídeo Semelhante ao Glucagon 1 , Macrófagos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica , Pericárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Animais , Pericárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Masculino , Macrófagos/metabolismo , Macrófagos/patologia , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Humanos , Feminino , Pessoa de Meia-Idade , Fenótipo , Dipeptidil Peptidase 4/metabolismo , Idoso , Técnicas de Cocultura , Adiposidade , Circulação Coronária , Transdução de Sinais , Microcirculação , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Vasos Coronários/diagnóstico por imagem , Incretinas/farmacologia , Microvasos/metabolismo , Microvasos/patologia , Células Cultivadas , Camundongos , Tecido Adiposo EpicárdicoRESUMO
Atopic dermatitis (AD) is a common inflammation skin disease that involves dysregulated interplay between immune cells and keratinocytes. Interleukin-38 (IL-38), a poorly characterized IL-1 family cytokine, its role and mechanism in the pathogenesis of AD is elusive. Here, we show that IL-38 is mainly secreted by epidermal keratinocytes and highly expressed in the skin and downregulated in AD lesions. We generated IL-38 keratinocyte-specific knockout mice (K14Cre/+-IL-38f/f ) and induced AD models by 2,4-dinitrofluorobenzene (DNFB). Unexpectedly, after treatment with DNFB, K14Cre/+-IL-38f/f mice were less susceptible to cutaneous inflammation of AD. Moreover, keratinocyte-specific deletion of IL-38 suppressed the migration of Langerhans cells (LCs) into lymph nodes which results in disturbed differentiation of CD4+T cells and decreased the infiltration of immune cells into AD lesions. LCs are a type of dendritic cell that reside specifically in the epidermis and regulate immune responses. We developed LC-like cells in vitro from mouse bone marrow (BM) and treated with recombined IL-38. The results show that IL-38 depended on IL-36R, activated the phosphorylated expression of IRAK4 and NF-κB P65 and upregulated the expression of CCR7 to promoting the migration of LCs, nevertheless, the upregulation disappeared with the addition of IL-36 receptor antagonist (IL-36RA), IRAK4 or NF-κB P65 inhibitor. Furthermore, after treatment with IRAK4 inhibitors, the experimental AD phenotypes were alleviated and so IRAK4 is considered a promising target for the treatment of inflammatory diseases. Overall, our findings indicated a potential pathway that IL-38 depends on IL-36R, leading to LCs migration to promote AD by upregulating CCR7 via IRAK4/NF-κB and implied the prevention and treatment of AD, supporting potential clinical utilization of IRAK4 inhibitors in AD treatment.
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Movimento Celular , Dermatite Atópica , Células de Langerhans , Animais , Dermatite Atópica/metabolismo , Células de Langerhans/metabolismo , Camundongos , Camundongos Knockout , Interleucina-1/metabolismo , Queratinócitos/metabolismo , Dinitrofluorbenzeno , NF-kappa B/metabolismo , Interleucinas/metabolismoRESUMO
Methyl-CpG-binding protein 2 (Mecp2) is an epigenetic modulator and numerous studies have explored its impact on the central nervous system manifestations. However, little attention has been given to its potential contributions to the peripheral nervous system (PNS). To investigate the regulation of Mecp2 in the PNS on specific central regions, we generated Mecp2fl/flAdvillincre mice with the sensory-neuron-specific deletion of the Mecp2 gene and found the mutant mice had a heightened sensitivity to temperature, which, however, did not affect the sense of motion, social behaviors, and anxiety-like behavior. Notably, in comparison to Mecp2fl/fl mice, Mecp2fl/flAdvillincre mice exhibited improved learning and memory abilities. The levels of hippocampal synaptophysin and PSD95 proteins were higher in Mecp2fl/flAdvillincre mice than in Mecp2fl/fl mice. Golgi staining revealed a significant increase in total spine density, and dendritic arborization in the hippocampal pyramidal neurons of Mecp2fl/flAdvillincre mice compared to Mecp2fl/fl mice. In addition, the activation of the BDNF-TrkB-CREB1 pathway was observed in the hippocampus and spinal cord of Mecp2fl/flAdvillincre mice. Intriguingly, the hippocampal BDNF/CREB1 signaling pathway in mutant mice was initiated within 5 days after birth. Our findings suggest a potential therapeutic strategy targeting the BDNF-TrkB-CREB1 signaling pathway and peripheral somasensory neurons to treat learning and cognitive deficits associated with Mecp2 disorders.
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Fator Neurotrófico Derivado do Encéfalo , Cognição , Espinhas Dendríticas , Hipocampo , Proteína 2 de Ligação a Metil-CpG , Animais , Proteína 2 de Ligação a Metil-CpG/metabolismo , Proteína 2 de Ligação a Metil-CpG/genética , Proteína 2 de Ligação a Metil-CpG/deficiência , Hipocampo/metabolismo , Hipocampo/patologia , Espinhas Dendríticas/metabolismo , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Receptoras Sensoriais/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Masculino , Transdução de Sinais , Camundongos Endogâmicos C57BL , Receptor trkB/metabolismo , Receptor trkB/genéticaRESUMO
OBJECTIVES: Clinical practice guideline (CPG) developers conduct systematic summaries of research evidence, providing them great capacity and ability to identify research priorities. We systematically analysed the reporting form and content of research priorities in CPGs related to knee osteoarthritis (KOA) to provide a valuable reference for guideline developers and clinicians. DESIGN: A methodological literature analysis was done and the characteristics of the reporting form and the content of the research priorities identified in KOA CPGs were summarised. DATA SOURCES: Six databases (PubMed, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang and Chinese Biomedical Literature Database) were searched for CPGs published from 1 January 2017 to 4 December 2022. The official websites of 40 authoritative orthopaedic societies, rheumatology societies and guideline development organisations were additionally searched. ELIGIBILITY CRITERIA: We included all KOA CPGs published in English or Chinese from 1 January 2017 that included at least one recommendation for KOA. We excluded duplicate publications, older versions of CPGs as well as guidance documents for guideline development. DATA EXTRACTION AND SYNTHESIS: Reviewers worked in pairs and independently screened and extracted the data. Descriptive statistics were used, and absolute frequencies and proportions of related items were calculated. RESULTS: 187 research priorities reported in 41 KOA CPGs were identified. 24 CPGs reported research priorities, of which 17 (41.5%) presented overall research priorities for the entire guideline rather than for specific recommendations. 110 (58.8%) research priorities were put forward due to lack of evidence. Meanwhile, more than 70% of the research priorities reflected the P (population) and I (intervention) structural elements, with 135 (72.2%) and 146 (78.1%), respectively. More than half of the research priorities (118, 63.8%) revolved around evaluating the efficacy of interventions. Research priorities primarily focused on physical activity (32, 17.3%), physical therapy (30, 16.2%), surgical therapy (27, 14.6%) and pharmacological treatment (26, 14.1%). CONCLUSIONS: Research priorities reported in KOA CPGs mainly focused on evaluating non-pharmacological interventions. There exists considerable room for improvement for a comprehensive and standardised generation and reporting of research priorities in KOA CPGs.
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Ortopedia , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/terapia , Publicações , Pesquisa , Guias de Prática Clínica como AssuntoRESUMO
Introduction: Signal peptide peptidase (SPP) is an intramembrane protease involved in a variety of biological processes, it participates in the processing of signal peptides after the release of the nascent protein to regulate the endoplasmic reticulum associated degradation (ERAD) pathway, binds misfolded membrane proteins, and aids in their clearance process. Additionally, it regulates normal immune surveillance and assists in the processing of viral proteins. Although SPP is essential for many viral infections, its role in silkworms remains unclear. Studying its role in the silkworm, Bombyx mori , may be helpful in breeding virus-resistant silkworms. Methods: First, we performed RT-qPCR to analyze the expression pattern of BmSPP. Subsequently, we inhibited BmSPP using the SPP inhibitor 1,3-di-(N-carboxybenzoyl-L-leucyl-L-leucylaminopropanone ((Z-LL)2-ketone) and downregulated the expression of BmSPP using CRISPR/Cas9 gene editing. Furthermore, we assessed the impact of these interventions on the proliferation of Bombyx mori nucleopolyhedrovirus (BmNPV). Results: We observed a decreased in the expression of BmSPP during viral proliferation. It was found that higher concentration of the inhibitor resulted in greater inhibition of BmNPV proliferation. The down-regulation of BmSPP in both in vivo and in vitro was found to affect the proliferation of BmNPV. In comparison to wild type silkworm, BmSPPKO silkworms exhibited a 12.4% reduction in mortality rate. Discussion: Collectively, this work demonstrates that BmSPP plays a negative regulatory role in silkworm resistance to BmNPV infection and is involved in virus proliferation and replication processes. This finding suggests that BmSPP servers as a target gene for BmNPV virus resistance in silkworms and can be utilized in resistance breeding programs.
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Bombyx , Nucleopoliedrovírus , Animais , Nucleopoliedrovírus/genética , Edição de Genes , Regulação para BaixoRESUMO
Introduction: Acute inflammatory storm is a major cause of myocardial ischemia/reperfusion (I/R) injury, with no effective treatment currently available. The excessive aggregation of neutrophils is correlated with an unfavorable prognosis in acute myocardial infarction (AMI) patients. Exosomes derived from mesenchymal stromal cells (MSC-Exo) have certain immunomodulatory potential and might be a therapeutic application. Therefore, we investigated the protective role of MSC-Exo in modulating neutrophil infiltration and formation of neutrophil extracellular traps (NETs) following myocardial I/R injury. Methods: Exosomes were isolated from the supernatant of MSCs using a gradient centrifugation method. We used flow cytometry, histochemistry, and immunofluorescence to detect the changes of neutrophils post-intravenous MSC-Exo injection. Additionally, cardiac magnetic resonance (CMR) and thioflavin S experiments were applied to detect microvascular obstruction (MVO). The NLR family pyrin domain containing 3 (NLRP3) inflammasome was examined for mechanism exploration. Primary neutrophils were extracted for in vitro experiment. Antibody of Ly6G was given to depleting the neutrophils in mice for verification the effect of MSC-Exo. Finally, we analyzed the MiRNA sequence of MSC-Exo and verified it in vitro. Results: MSC-Exo administration reduced neutrophil infiltration and NETs formation after myocardial I/R. MSC-Exo treatment also could attenuate the activation of NLRP3 inflammasome both in vivo and in vitro. At the same time, the infarction size and MVO following I/R injury were reduced by MSC-Exo. Moreover, systemic depletion of neutrophils partly negated the therapeutic effects of MSC-Exo. Up-regulation of miR-199 in neutrophils has been shown to decrease the expression of NETs formation after stimulation. Discussion: Our results demonstrated that MSC-Exo mitigated myocardial I/R injury in mice by modulating neutrophil infiltration and NETs formation. This study provides novel insights into the potential therapeutic application of MSC-Exo for myocardial ischemia/reperfusion injury.
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Exossomos , Armadilhas Extracelulares , MicroRNAs , Traumatismo por Reperfusão Miocárdica , Traumatismo por Reperfusão , Humanos , Camundongos , Animais , Traumatismo por Reperfusão Miocárdica/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Exossomos/metabolismo , Armadilhas Extracelulares/metabolismo , Infiltração de Neutrófilos , MicroRNAs/genética , Traumatismo por Reperfusão/patologiaRESUMO
OBJECTIVES: To compared the presentation of research priorities in the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) clinical practice guidelines (CPGs) developed under the guidance of the GRADE working group or its two co-chair, and the Chinese CPGs. METHODS: This was a methodological empirical analysis. We searched PubMed, Embase, and four Chinese databases (Wanfang, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure and Chinese Biomedical Literature Database) and retrieved nine Chinese guideline databases or Society websites as well as GRADE Pro websites. We included all eligible GRADE CPGs and a random sample of double number of Chinese CPGs, published 2018 to 2022. The reviewers independently screened and extracted the data, and we summarized and analyzed the reporting on the research priorities in the CPGs. RESULTS: Of the 135 eligible CPGs (45 GRADE CPGs and 90 Chinese CPGs), 668, 138 research priorities were identified respectively. More than 70% of the research priorities in GRADE CPGs and Chinese CPGs had population and intervention (PI) structure. 99 (14.8%) of GRADE CPG research priorities had PIC structures, compared with only 4(2.9%) in Chinese. And 28.4% (190) GRADE CPG research priorities reflected comparisons between PICO elements, approximately double those in Chinese. The types of research priorities among GRADE CPGs and Chinese CPGs were mostly focused on the efficacy of interventions, and the type of comparative effectiveness in the GRADE research priorities was double those in Chinese. CONCLUSIONS: There was still considerable room for improvement in the developing and reporting of research priorities in Chinese CPGs. Key PICO elements were inadequately presented, with more attention on intervention efficacy and insufficient consideration given to values, preferences, health equity, and feasibility. Identifying and reporting of research priorities deserves greater effort in the future.
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Publicações , Projetos de Pesquisa , Humanos , China , Bases de Dados FactuaisRESUMO
A photocatalytic three-component sulfonyl peroxidation of alkenes with N-sulfonyl ketimines and tert-butyl hydroperoxide is reported. The reaction takes place via the photoinduced EnT process, which allows the efficient synthesis of a variety of ß-peroxyl sulfones under mild reaction conditions in the absence of a transition metal catalyst. The downstream derivatizations of the peroxides were also performed. Furthermore, the utility of this protocol was manifested by the synthesis of 11ß-HSD1 inhibitor and the antiprostate cancer drug bicalutamide.
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Covering: up to 2023Conjugated polyynes are natural compounds characterized by alternating single and triple carbon-carbon bonds, endowing them with distinct physicochemical traits and a range of biological activities. While traditionally sourced mainly from plants, recent investigations have revealed many compounds originating from bacterial strains. This review synthesizes current research on bacterial-derived conjugated polyynes, delving into their biosynthetic routes, underscoring the variety in their molecular structures, and examining their potential applications in biotechnology. Additionally, we outline future directions for metabolic and protein engineering to establish more robust and stable platforms for their production.
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Bactérias , Poli-Inos , Bactérias/metabolismo , Poli-Inos/química , Poli-Inos/metabolismo , Poli-Inos/farmacologia , Estrutura Molecular , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Vias Biossintéticas , Biotecnologia/métodosRESUMO
BACKGROUND: The overall comprehensive consideration of the factors influencing the recommendations in the traditional Chinese medicine (TCM) guidelines remains poorly studied. This study systematically evaluate the factors influencing recommendations formation in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) clinical practice guidelines (CPGs) and TCM CPGs. METHODS: This was a methodological review in which we searched six databases and multiple related websites. The GRADE CPGs were identified as the guidelines developed by the GRADE Working Group or the two Co-Chairs. For the TCM CPGs, we randomly selected guidelines that were published by the TCM or integrative medicine academic societies from China mainland (published by the TCM or integrative medicine academic societies of China mainland). Two reviewers independently screened and extracted data. We included CPGs published in 2018-2022. We extracted information on the influencing factors of evidence to recommendation and conducted the analyses using descriptive statistics and calculated the proportion of relevant items by IBM SPSS Statistics and Microsoft Excel to compare the differences between the GRADE CPGs and the TCM CPGs. RESULTS: Forty-five GRADE CPGs (including 912 recommendations) and 88 TCM CPGs (including 2452 recommendations) were included. TCM recommendations mainly considered the four key determinants of desirable anticipated effects, undesirable anticipated effects, balance between desirable and undesirable effects, certainty of evidence, with less than 20% of other dimensions. And TCM CPGs presented more strong recommendations (for or against) and inappropriate discordant recommendations than GRADE CPGs. GRADE CPGs were more comprehensive considered about the factors affecting the recommendations, and considered more than 70% of all factors in the evidence to recommendation. CONCLUSIONS: The TCM CPGs lack a comprehensive consideration of multiple influencing determinants from evidence to recommendations. In the future, the correct application of the GRADE approaches should be emphasized.
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Medicina Integrativa , Medicina Tradicional Chinesa , China , Bases de Dados FactuaisRESUMO
Although the formation control of multi-agent systems has been widely investigated from various aspects, the problem is still not well resolved, especially for the case of distributed output-feedback formation controller design without input information exchange among neighboring agents. Using relative output information, this paper presents a novel distributed reduced-order estimation of the formation error at a predefined time. Based on the proposed distributed observer, a neural-network-based formation controller is then designed for multi-agent systems with connected graphs. The results are verified by both theoretical demonstration and simulation example.
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Optogenetics is a novel biotechnology widely used to precisely manipulate a specific peripheral sensory neuron or neural circuit. However, the use of optogenetics to assess the therapeutic efficacy of analgesics is elusive. In this study, we generated a transgenic mouse stain in which all primary somatosensory neurons can be optogenetically activated to mimic neuronal hyperactivation in the neuropathic pain state for the assessment of analgesic effects of drugs. A transgenic mouse was generated using the advillin-Cre line mated with the Ai32 strain, in which channelrhodopsin-2 fused to enhanced yellow fluorescence protein (ChR2-EYFP) was conditionally expressed in all types of primary somatosensory neurons (advillincre/ChR2+/+). Immunofluorescence and transdermal photostimulation on the hindpaws were used to verify the transgenic mice. Optical stimulation to evoke pain-like paw withdrawal latency was used to assess the analgesic effects of a series of drugs. Injury- and pain-related molecular biomarkers were investigated with immunohistofluorescence. We found that the expression of ChR2-EYFP was observed in many primary afferents of paw skin and sciatic nerves and in primary sensory neurons and laminae I and II of the spinal dorsal horns in advillincre/ChR2+/+ mice. Transdermal blue light stimulation of the transgenic mouse hindpaw evoked nocifensive paw withdrawal behavior. Treatment with gabapentin, some channel blockers, and local anesthetics, but not opioids or COX-1/2 inhibitors, prolonged the paw withdrawal latency in the transgenic mice. The analgesic effect of gabapentin was also verified by the decreased expression of injury- and pain-related molecular biomarkers. These optogenetic mice provide a promising model for assessing the therapeutic efficacy of analgesics in neuropathic pain.
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Cells living in geometrically confined microenvironments are ubiquitous in various physiological processes, e.g., wound closure. However, it remains unclear whether and how spatially geometric constraints on host cells regulate bacteria-host interactions. Here, we reveal that interactions between bacteria and spatially constrained cell monolayers exhibit strong spatial heterogeneity, and that bacteria tend to adhere to these cells near the outer edges of confined monolayers. The bacterial adhesion force near the edges of the micropatterned monolayers is up to 75 nN, which is ~3 times higher than that at the centers, depending on the underlying substrate rigidities. Single-cell RNA sequencing experiments indicate that spatially heterogeneous expression of collagen IV with significant edge effects is responsible for the location-dependent bacterial adhesion. Finally, we show that collagen IV inhibitors can potentially be utilized as adjuvants to reduce bacterial adhesion and thus markedly enhance the efficacy of antibiotics, as demonstrated in animal experiments.
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Aderência Bacteriana , Colágeno , Animais , Aderência Bacteriana/fisiologia , Colágeno/metabolismo , Fenômenos Mecânicos , Bactérias/metabolismo , Adesão CelularRESUMO
BACKGROUND: Patients with a history of hypertension have elevated inflammation and a worse prognosis after acute myocardial infarction (AMI). Regulatory T cells (Tregs) are reported to lose their immunosuppressive capacity under pathological conditions. However, whether hypertension leads to Treg dysfunction, thus accelerating myocardial ischemia-reperfusion injury, is still unknown. METHODS: Studies were performed in hypertensive rats and mice with myocardial ischemia-reperfusion injury. The frequencies and phenotypes of Tregs were analyzed by flow cytometry and immunohistochemistry. Reconstruction Treg experiments were performed to evaluate the effect of Tregs on ischemia-reperfusion injury. Patients with AMI were enrolled to assess circulating Tregs, inflammatory cytokines, and cardiac function. RESULTS: In this study, we found that hypertension leads to proinflammatory Th1 (T helper 1 cell)-like Treg subsets with compromised suppressive capacity. Reconstruction Treg experiments identified that dysfunctional Tregs induced by hypertension play a pathogenic role in the progression of myocardial ischemia-reperfusion injury. In particular, we identified HDAC6 (histone deacetylase 6) as a central regulator in the perturbed Tregs. Clinical studies revealed that the hypertension-induced reduction in circulating Tregs strongly correlated with the higher occurrence rate of microvascular obstruction in AMI patients with hypertension. CONCLUSIONS: Our study provided promising clues to explain the poor prognosis of hypertensive AMI patients due to alterations in Tregs. Targeting disturbed Tregs may be a new strategy to treat AMI patients with hypertension.
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Hipertensão , Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Humanos , Animais , Camundongos , Ratos , Linfócitos T Reguladores , Citocinas , Citometria de FluxoRESUMO
Here we report a strategy for the facile assembly of fused 3-trifluoromethyl-1,2,4-triazoles, which are difficult to synthesize using traditional strategies, in 50-96% yields through a triethylamine-promoted intermolecular [3 + 2] cycloaddition pathway. This protocol features high efficiency, good functional group tolerance, mild conditions, and easy operation. Furthermore, a gram-scale reaction and product derivatizations were carried out smoothly to illustrate the practicability of this method.
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Background: Oxidative stress is a key risk factor for visual impairment and consuming dietary antioxidant-rich foods may help in managing visual impairments. However, a limited number of studies have investigated the effect of dietary antioxidant-rich food including grapes on eye health in older adults. Objectives: To assess the effects on macular pigment accumulation of regular consumption of grapes in Singapore older adults. Methods: This was a 16 week, double-blind, randomized, placebo-controlled trial. Thirty-four Singapore older adults were randomized into regularly consuming either 46 g day-1 of freeze-dried table grape powder (the intervention group) or the same amount of placebo powder (the control group). Macular pigment optical density (MPOD), skin carotenoid status, advanced glycation end product (AGEs) status and dietary lutein intake were assessed every 4 weeks, and plasma lutein concentration, total antioxidant capacity and total phenolic content were measured every 8 weeks. Results: A significant time effect (p = 0.007) was observed for MPOD, and this is largely attributed to the improvement in the MPOD for the intervention group, as a significant increase was observed only in this group (week 0: 0.56 ± 0.04 D.U.; week 16: 0.61 ± 0.04 D.U., p < 0.01). Additionally, a significant increase in plasma total antioxidant capacity (week 0: 0.26 ± 0.13 mM TEAC; week 16: 0.36 ± 0.20 mM TEAC, p < 0.01) and total phenolic content (week 0: 10.50 ± 0.44 mg L-1 GAE; week 16: 12.58 ± 0.55 mg L-1 GAE, p < 0.001) was observed for the intervention group only. In contrast, a significant increase in skin AGE status was observed in the control group (week 0: 2.47 ± 0.24; week 16: 2.99 ± 0.12, p < 0.05) while this was mitigated in the intervention group. There were no differences in dietary lutein intake, plasma lutein concentration and skin carotenoid status between groups throughout the study. Conclusions: Regular intake of grapes may improve eye health in Singapore older adults, specifically in augmenting MPOD, which can be explained by an increase in plasma total antioxidant capacity and phenolic content, and the downregulation of AGEs. This study was registered at clinicatrials.gov as NCT05064865.
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Pigmento Macular , Vitis , Antioxidantes , Luteína , Pós , Singapura , Aditivos Alimentares , Fenóis , Produtos Finais de Glicação AvançadaRESUMO
OBJECTIVE: This study aims to investigate the 10-year trends and disparities in underweight, overweight, and obesity among older adults aged 65 years and older in China from 2008 to 2018. METHODS: We used four waves (2008, 2011, 2014, and 2018) of data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a national community-based cross-sectional survey conducted every 2-3 years. Body weight and height were measured by trained assessors following standardized procedures. BMI was calculated and divided into underweight (< 18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obese (≥ 30.0 kg/m2) according to WHO reference. Multinomial logistic regression models were used to examine factors related with abnormal BMI groups, after adjusting for potential confounders. RESULTS: Among 46,543 older adults in China, the prevalence rates of underweight decreased with each survey year from 2008 to 2018, declining from 20.05 to 7.87% (p < 0.001). In contrast, the prevalence rates of overweight and obesity showed an increasing trend (all p < 0.001). Specifically, the prevalence of overweight rose from 12.82% to 2008 to 28.45% in 2018, and the prevalence of obesity increased from 1.62% to 2008 to 4.95% in 2018. In the multinomial logistic regression model, survey year, gender, residence, marital status, economic status, numbers of chronic diseases, smoking status, sleep quality, and functional disability were factors related with obesity. CONCLUSION: The prevalence rates of overweight and obesity were increasing while the prevalence of underweight and normal weight significantly decreased from 2008 to 2018 among older adults in China, which poses a huge challenge for chronic disease. There is an urgent need for intervention policy planning and early prevention of abnormal body weight for the preparation of an aging society.
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Sobrepeso , Magreza , Idoso , Humanos , Índice de Massa Corporal , Peso Corporal , China/epidemiologia , Estudos Transversais , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Prevalência , Fatores de Risco , Magreza/epidemiologiaRESUMO
AIM: We investigate how the confirmation of expectations about digital technology in the workplace affects the career intentions of nursing students. We also explore the role of task fit in mediating (1) digital technology satisfaction and job satisfaction and (2) digital technology satisfaction and career intentions. BACKGROUND: The turnover of graduating geriatric nursing students is very high and rising. To support the work of nursing staff, elderly care institutions are beginning to adopt digital technologies that aid in nursing tasks. However, it is unclear whether students' perceptions of those digital technologies have an impact on their career intentions. DESIGN: This is a cross-sectional study. METHODS: We recruited 549 geriatric nursing students. Data were collected from December 2022 to March 2023. The questionnaire included seven sections: expectation confirmation, perceived usefulness, perceived safety, digital technology satisfaction, task fit, job satisfaction and career intentions. The validity and reliability of the model were confirmed. RESULTS: The results show that the confirmation of students' expectations for the digital technology used in elderly care services has a positive impact on their career intentions. However, the results do not confirm the impact of perceived security on digital technology satisfaction, or the effect of job satisfaction on career intentions. CONCLUSION: Elderly care institutions and educators should monitor the current state of the digital work environment to ensure that it can adequately support students in their work. They should ensure the use of advanced and appropriate technology tools in teaching and clinical environments to provide a richer and more vivid learning experience. These initiatives can support nursing students in their transition from school to practice and increase their willingness to stay in the profession.
Assuntos
Intenção , Estudantes de Enfermagem , Humanos , Idoso , Estudos Transversais , Reprodutibilidade dos Testes , Satisfação no Emprego , Inquéritos e Questionários , Escolha da ProfissãoRESUMO
Background: Poor sleep status as a common concern is a risk factor for many health problems among older people. China with an aging society lacks relevant nationwide data on the sleep status among older people. Therefore, the purpose of this study was to investigate trends and disparities in sleep quality and duration among older adults, and exploring influencing factors of poor sleep in China between 2008 and 2018. Method: We used the four-waves data of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2008 to 2018. Sleep quality and average sleep hours per day was investigated by using questionnaires in the CLHLS. We categorized sleep duration as three groups including ≤5 h (short duration), 5-9 h (normal duration), or ≥9 h (long duration) per day. Multivariate logistic regression models were used to examine trends and risk factors of poor sleep quality, short sleep duration, and long sleep duration. Results: The prevalence of poor sleep quality significantly increased from 34.87% in 2008 to 47.67% in 2018 (p < 0.05). Short sleep duration significantly increased from 5.29 to 8.37%, whereas long sleep duration decreased from 28.77 to 19.27%. Multivariate analysis showed that female sex, poor economic status, a greater number of chronic diseases, underweight, poor self-reported quality of life, and poor self-reported health were associated with poor sleep quality and short sleep duration (p < 0.05). Conclusion: Our findings revealed that older adults had increased prevalence of poor sleep quality and short sleep duration from 2008 to 2018. More attention should be paid to the increased sleep problems among older adults and early interventions should be made to improve sleep quality and guarantee enough sleep time.