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Staphylococcus aureus (S. aureus) infections are a serious threat to human health. The development of rapid and sensitive detection methods for pathogenic bacteria is crucial for accurate drug administration. In this research, by combining the advantages of enzyme-linked immunosorbent assay (ELISA), we synthesized nanozymes with high catalytic performance, namely pomegranate seed-structured bimetallic gold-platinum nanomaterials (Ps-PtAu NPs), which can catalyze a colorless TMB substrate into oxidized TMB (oxTMB) with blue color to achieve colorimetric analysis of S. aureus. Under the optimal conditions, the proposed biosensor could quantitatively detect S. aureus at levels ranging from 1.0 × 101 to 1.0 × 106 CFU mL-1 with a limit of detection (LOD) of 3.9 CFU mL-1. Then, an integrated color picker APP on a smartphone enables on-site point-of-care testing (POCT) of S. aureus with LOD as low as 1 CFU mL-1. Meanwhile, the proposed biosensor is successfully applied to the detection of S. aureus in clinical samples with high sensitivity and specificity.
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Técnicas Biossensoriais , Punica granatum , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Colorimetria/métodos , Imunoensaio/métodos , Infecções Estafilocócicas/microbiologia , Técnicas Biossensoriais/métodosRESUMO
Yield and quality are two crucial breeding objects of wheat therein grain weight and grain protein content (GPC) are two key relevant factors correspondingly. Investigations of their genetic mechanisms represent special significance for breeding. In this study, 199 F2 plants and corresponding F2:3 families derived from Nongda3753 (ND3753) and its EMS-generated mutant 564 (M564) were used to investigate the genetic basis of larger grain and higher GPC of M564. QTL analysis identified a total of 33 environmentally stable QTLs related to thousand grain weight (TGW), grain area (GA), grain circle (GC), grain length (GL), grain width (GW), and GPC on chromosomes 1B, 2A, 2B, 4D, 6B, and 7D, respectively, among which QGw.cau-6B.1, QTgw.cau-6B.1, QGa.cau-6B.1, and QGc.cau-6B.1 shared overlap confidence interval on chromosome 6B. This interval contained the TaGW2 gene playing the same role as the QTLs, so TaGW2-6B was cloned and sequenced. Sequence alignment revealed two G/A SNPs between two parents, among which the SNP in the seventh exon led to a premature termination in M564. A KASP marker was developed based on the SNP, and single-marker analysis on biparental populations showed that the mutant allele could significantly increase GW and TGW, but had no effect on GPC. Distribution detection of the mutant allele through KASP marker genotyping and sequence alignment against databases ascertained that no materials harbored this allele within natural populations. This allele was subsequently introduced into three different varieties through molecular marker-assisted backcrossing, and it was revealed that the allele had a significant effect on simultaneously increasing GW, TGW, and even GPC in all of three backgrounds. Summing up the above, it could be concluded that a novel elite allele of TaGW2-6B was artificially created and might play an important role in wheat breeding for high yield and quality. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01455-y.
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INTRODUCTION: Hypertension can accelerate and aggravate the process of arterial ageing and calcification. However, the mechanism behind has yet to be well elucidated. METHODS: Here, we monitored the dynamic changes of fibronectin (FN)/α5 integrin, bone morphogenetic protein 2/matrix Gla protein (BMP2/MGP), and Runx2 in the aorta of spontaneously hypertensive rats (SHRs) and thoracic aortic vascular smooth muscle cells (VSMCs), also the phenotypic transformation of VSMCs during the process of arterial ageing and calcification. Further, study on arterial ageing and calcification through antagonist experiments at the molecular level was explored. RESULTS: We found extracellular FN and its α5 integrin receptor expressions were positively associated with arterial ageing and calcification in SHR during ageing, as well in VSMCs from SHR in vitro. Integrin receptor inhibitor of GRGDSP would delay this arterial ageing and calcification process. Moreover, the elevated FN and α5 integrin receptor expression evoked the disequilibrium of BMP2/MGP, where the expression of BMP2, a potent osteogenic inducer, increased while MGP, a calcification inhibitor, decreased. Furthermore, it was followed by the upregulation of Runx2 and the phenotypic transformation of VSMCs from the contractile phenotype into the osteoblast-like cells. Notably, BMP2 antagonist of rmNoggin was sufficient to ameliorate the ageing and calcification process of VSMCs and exogenous BMP2-adding accelerate and aggregate the process. CONCLUSION: Our study revealed that hypertension-associated arterial ageing and calcification might be a consequence that hypertension up-regulated FN and its high binding affinity integrin α5 receptor in the aortic wall, which in turn aggravated the imbalance of BMP2/MGP, promoted the transcription of Runx2, and induced the phenotypic transformation of VSMCs from the contractile phenotype into the osteoblast-like cells. Our study would provide insights into hypertension-associated arterial ageing and calcification and shed new light on the control of arterial calcification, especially for those with hypertension.
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Envelhecimento , Proteína Morfogenética Óssea 2 , Subunidade alfa 1 de Fator de Ligação ao Core , Fibronectinas , Hipertensão , Proteína de Matriz Gla , Músculo Liso Vascular , Fenótipo , Ratos Endogâmicos SHR , Calcificação Vascular , Proteína Morfogenética Óssea 2/metabolismo , Animais , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Ratos , Fibronectinas/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia , Calcificação Vascular/etiologia , Masculino , Proteínas da Matriz Extracelular/metabolismo , Miócitos de Músculo Liso/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Integrina alfa5/metabolismo , Integrina alfa5/genética , Células CultivadasRESUMO
OBJECTIVE: This study was performed to explore the differences in the clinical characteristics and oxidative stress indicators, inflammatory factors, and pathological proteins in serum between Parkinson's disease (PD) with anxiety (PD-A) and with no anxiety (PD-NA) patients, and further correlations among clinical characteristics and above variables were analyzed in PD-A and PD-NA groups. METHODS: A total of 121 patients with PD were enrolled in this study and assessed by the Hamilton Anxiety Scale (14 items) (HAMA-14). These patients were divided into PD-A and PD-NA groups according to a cut-off point of 7 of HAMA-14. Demographic variables were collected, and clinical symptoms were assessed by multiple rating scales. The levels of free radicals, inflammatory factors, and pathological proteins in serum were measured by chemical colorimetric method and enzyme-linked immunosorbent assay (ELISA). The differences of above variables were compared between PD-A and PD-NA groups, and the correlations of clinical symptoms with the abovevariables were analyzed in PD-A and PD-NA groups. RESULTS: The frequency of PD-A was 62.81%. PD-A group exhibited significantly impaired motor dysfunction and multiple non-motor symptoms, including fatigue, sleep behavior disorder, restless leg syndrome and autonomic dysfunction, and dramatically compromised activities of daily living compard with PD-NA group. PD-A group displayed prominently increasedlevels of hydroxyl radical (·OH) and tumor necrosis factor (TNF)-α, and a decreased nitric oxide (NO) level in serum compared with PD-NA group (P<0.001, P = 0.001, P= 0.027, respectively). ·OH, NO, and TNF-α were identified as the risk factors of PD-A (OR = 1.005, P = 0.036; OR = 0.956, P = 0.017; OR = 1.039, P = 0.033, respectively). In PD patients, HAMA-14 score was significantly and positively correlated with the levels of ·OH and TNF-α in serum (P<0.001, P = 0.002, respectively). In PD-A group, ·OH level was significantly and negatively correlated with Aß1-42 level, while TNF-α level was significantly and positively correlated with P-tau (S396) level in serum. CONCLUSIONS: The frequency of PD-A is high. PD-A patients present more severe motor dysfunction and multiple non-motor symptoms, and poorer activities of daily living. The increased levels of ·OH and TNF-α levels and the decreased NO level in serum are all associated with more severe anxiety in PD patients.Findings from this study may provide in-depth insights into the clinical characteristics, underlying mechanisms of PD-A, and potential correlations among anxiety, oxidative stress, inflammation, and cognitive decline in PD patients.
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Ansiedade , Inflamação , Estresse Oxidativo , Doença de Parkinson , Humanos , Doença de Parkinson/sangue , Doença de Parkinson/psicologia , Doença de Parkinson/diagnóstico , Masculino , Feminino , Estresse Oxidativo/fisiologia , Idoso , Pessoa de Meia-Idade , Ansiedade/sangue , Ansiedade/psicologia , Inflamação/sangueRESUMO
Apple ring rot, one of the most common apple postharvest diseases during storage, is caused by Botryosphaeria dothidea. Presently, the disease management is primarily dependent on chemical fungicide application. Here we demonstrated an endophyte bacterium Bacillus tequilensis QNF2, isolated from Chinese leek (Allium tuberosum) roots considerably suppressed B. dothidea mycelial growth, with the highest suppression of 73.56 % and 99.5 % in the PDA and PDB medium, respectively in vitro confront experiments. In in vivo experiments, B. tequilensis QNF2 exhibited a control efficacy of 88.52 % and 100 % on ring rot disease on postharvest apple fruits inoculated with B. dothidea disc and dipped into B. dothidea culture, respectively. In addition, B. tequilensis QNF2 volatile organic compounds (VOCs) also manifested markedly inhibition against B. dothidea mycelial growth and the ring rot on postharvest apple fruits. Moreover, B. tequilensis QNF2 severely damaged the mycelial morphology of B. dothidea. Finally, B. tequilensis QNF2 significantly repressed the expression of six pathogenicity-related genes, such as adh, aldh, aldh3, galm, pdc1, pdc2, involved in glycolysis/gluconeogenesis of B. dothidea. The findings of the study proved that B. tequilensis QNF2 was a promising alternative for controlling apple ring rot of postharvest apple fruit.
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Ascomicetos , Bacillus , Endófitos , Frutas , Malus , Doenças das Plantas , Malus/microbiologia , Doenças das Plantas/microbiologia , Ascomicetos/crescimento & desenvolvimento , Ascomicetos/efeitos dos fármacos , Ascomicetos/genética , Ascomicetos/fisiologia , Bacillus/genética , Bacillus/fisiologia , Bacillus/isolamento & purificação , Endófitos/genética , Endófitos/metabolismo , Endófitos/isolamento & purificação , Endófitos/classificação , Endófitos/fisiologia , Frutas/microbiologia , Compostos Orgânicos Voláteis/farmacologia , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/análise , Antibiose , Micélio/crescimento & desenvolvimento , Micélio/efeitos dos fármacosRESUMO
Deep brain stimulation (DBS) is a common therapy for managing Parkinson's disease (PD) in clinical practice. However, a complete understanding of its mode of action is still needed. DBS is believed to work primarily through electrical and neurochemical pathways. Furthermore, DBS has other mechanisms of action. This review explores the fundamental concepts and applications of DBS in treating PD, including its mechanisms, clinical implications, and recent research.
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Estimulação Encefálica Profunda , Doença de Parkinson , Doença de Parkinson/terapia , Doença de Parkinson/fisiopatologia , Humanos , Encéfalo/fisiopatologia , AnimaisRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a major public health problem due to the high incidence affecting approximately one-third of the world's population. NAFLD is usually linked to obesity and excessive weight. A subset of patients with NAFLD expresses normal or low body mass index; thus, the condition is called non-obese NAFLD or lean NAFLD. However, patients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. Furthermore, preclinical results from non-obese animal models with NAFLD are unclear. Gut microbiota and their metabolites in non-obese/lean-NAFLD patients differ from those in obese NAFLD patients. Therefore, we analyzed the biochemical indices, intestinal flora, and intestinal metabolites in a non-obese NAFLD mouse model established using a methionine-choline-deficient (MCD) diet. The significantly lean MCD mice had a remarkable fatty liver with lower serum triglyceride and free fatty acid levels, as well as higher alanine transaminase and aspartate transaminase levels than normal mice. 16S RNA sequencing of fecal DNA showed that the overall richness and diversity of the intestinal flora decreased in MCD mice, whereas the Firmicutes:Bacteroidota ratio was increased. g_Tuzzerella, s_Bifidobacterium pseudolongum, and s_Faecalibaculum rodentium were the predominant species in non-obese NAFLD mice. Fecal metabolomics using liquid chromatography-tandem mass spectrometry revealed the potential biomarkers for the prognosis and diagnosis of non-obese NAFLD, including high levels of tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4'-phosphate, and low levels of 3-carbamoyl-2-phenylpropionaldehyde, N-succinyl-L,L-2,6-diaminopimelate, 4-methyl-5-thiazoleethanol, homogentisic acid, and estriol. Our findings could be useful to identify and develop drugs to treat non-obese NAFLD and lean NAFLD. IMPORTANCE: Patients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. In fact, about 40% of people with NAFLD worldwide are non-obese, and nearly one-fifth are lean. Lean NAFLD unfortunately may be unnoticed for years and remains undetected until hepatic damage is advanced and the prognosis is compromised. This study focused on the lean NAFLD, screened therapeutic agents, and biomarkers for the prognosis and diagnosis using MCD-induced male C57BL/6J mice. The metabolites tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4'-phosphate, together with the predominant flora including g_Tuzzerella, s_Bifidobacterium pseudolongum, and s_Faecalibaculum rodentium, were specific in non-obese NAFLD mice and might be used as targets for non-obese NAFLD drug exploration. This study is particularly significant for non-obese NAFLDs that need to be more actively noticed and vigilant.
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Bifidobacterium , Firmicutes , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Panteteína/análogos & derivados , Tiramina/análogos & derivados , Humanos , Animais , Camundongos , Masculino , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Microbioma Gastrointestinal/genética , Camundongos Endogâmicos C57BL , Obesidade/complicações , Biomarcadores , Colina , FosfatosRESUMO
This study focuses on the characteristics of foam generation, flow, and plugging in different reservoir fracture environments. Through visual physical model experiments and stone core displacement experiments, we analyze the flow regeneration of foam in a simulated reservoir fracture environment as well as its sealing and sweeping mechanisms. The findings reveal that low permeability reservoirs, with their smaller and more intricate fracture structures, are conducive to the generation of high-strength foam. This is due to the stronger shear effect of these fracture structures on the injected surfactant and gas mixture system, resulting in a denser foam system. Consequently, low permeability reservoirs facilitate a series of mechanisms that enhance the fluid sweep efficiency. Furthermore, the experiments demonstrate that higher reservoir fracture roughness intensifies the shear disturbance effect on the injected fluid. This disturbance aids in foam regeneration, increases the flow resistance of the foam, and helps to plug high permeability channels. As a result, the foam optimizes the injection-production profile and improves the fluid sweep efficiency. Stone core displacement experiments further illustrate that during foam flooding, the foam liquid film encapsulates the gas phase, thereby obstructing fluid channeling through the Jamin effect. This forces the subsequently injected fluid into other low-permeability fractures, overcoming the shielding effect of high-permeability fractures on low-permeability fractures. Consequently, this improves the fluid diversion rate of low permeability fractures, effectively inhibiting fluid cross-flow and enhancing sweep efficiency. These experimental results highlight the advantages of foam flooding in the development of complex reservoirs with low permeability fracture structures, demonstrating its efficacy in inhibiting fluid cross-flow and optimizing the injection-production profile.
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Perovskite light-emitting diodes (PeLEDs) have shown great potential in the display domain due to their wide color gamut, narrow emission, and low cost. In current PeLEDs manufacturing methods, thermal evaporation shows great competitiveness with its advantages of easy patterning, production line compatibility, and solvent-free processability. However, the development of thermally evaporated blue PeLEDs is limited by their low radiative recombination rate and high defect density. Herein, we report high-performance thermally evaporated blue PeLEDs by in situ introduction of ammonium cations. We confirm that phenethylammonium (PEA+) has lower adsorption energy, which significantly reduces the low-n phases in a quasi-2D perovskite film. The energy transfer rate is also promoted by the PEA+ addition. As a result, we fabricate blue PeLEDs with an external quantum efficiency of 1.56% by thermal evaporation. The strategy of arranging phase distribution could benefit the industrialization of full-color PeLEDs.
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BACKGROUND: Tumor budding (TB) is a negative prognostic factor in colorectal cancer; however, its prognostic impact following neoadjuvant therapy for patients with rectal cancer remains unclear. This study aims to assess the prognostic impact of TB and the correlation between TB and other pathological features in patients with rectal cancer after neoadjuvant therapy. METHODS: A comprehensive search of PubMed, Embase, Cochrane, Scopus, CNKI, Wanfang, and ClinicalKey databases was conducted for studies on the prognosis of TB in rectal cancer after neoadjuvant therapy from the inception of the databases to January 2023, and the final literature included was determined using predefined criteria. Quality assessment of the studies included, extraction of general and prognostic information from them, and meta-analyses were carried out progressively. RESULTS: A total of 11 studies were included, and the results of the meta-analysis showed that high-grade tumor budding (TB-1) increased the risk of poor 5-year disease-free survival (HR = 1.75, 95% CI 1.38-2.22, P < 0.00001), 5-year overall survival (HR = 1.77, 95% CI 1.21-2.59, P = 0.003), local recurrence (OR = 4.15, 95% CI 1.47-11.75, P = 0.007), and distant metastasis (OR = 5.36, 95% CI 2.51-11.44, P < 0.0001) in patients with rectal cancer after neoadjuvant therapy. TB-1 was significantly associated with poor differentiation and lymphatic, perineural, and venous invasion. CONCLUSION: Tumor budding is significantly correlated with unfavorable prognosis and poor pathological characteristics following neoadjuvant therapy for rectal cancer. We anticipate more high-quality, prospective studies in the future to confirm our findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022377564.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Bases de Dados Factuais , Prognóstico , Estudos Prospectivos , Neoplasias Retais/diagnóstico , Neoplasias Retais/terapiaRESUMO
Age significantly affects the prognosis of patients with rectal cancer after radical excision (RE), and local excision (LE) is an alternative surgical procedure to RE. To compare the survival prognosis in different age groups of LE versus RE for rectal cancer. Patients diagnosed with rectal adenocarcinoma treated by LE or RE from 2010 to 2017 were obtained from the SEER database. The primary outcomes are 5-year OS and CSS. A total of 11,170 patients were eventually included, and there were 490 patients in LE and RE groups, respectively, after 1:1 propensity score matching. The 5-year OS and CSS after LE were significantly better in < 50 years and 50-66 years groups than in > 66 years group (5-year OS: 95.70% vs 88.40% vs 67.00%, P < 0.001; 5-year CSS: 95.70% vs 96.30% vs 82.60%, P < 0.001). No statistical significance was found for the differences in 5-year OS and CSS between LE and RE in < 50, 50-66, and > 66 years group (P > 0.05). Multivariate analysis showed age > 66 years, poorly differentiated or undifferentiated (Grade III/IV), and tumor size 3 to 5 cm was independent risk factors for 5-year OS after LE; age > 66 years, perineural invasion, and tumor size 3 to 5 cm were the 5-year CSS independent risk factors for after LE. We found that the survival prognosis of younger rectal cancer patients treated with LE was significantly better than older (> 66 years) patients, and the survival prognosis of rectal cancer patients in the three age groups was similar between LE and RE.
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Adenocarcinoma , Neoplasias Retais , Programa de SEER , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Pessoa de Meia-Idade , Idoso , Fatores Etários , Prognóstico , Masculino , Feminino , Adenocarcinoma/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Taxa de Sobrevida , Pontuação de Propensão , Fatores de Risco , Adulto , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Bases de Dados FactuaisRESUMO
Background: The coronavirus disease 2019 (COVID-19) pandemic subverted people's lives and potentially affected the management and prognosis of pre-existing dermatoses. The study aims to identify factors influencing the outcomes of dermatoses during a rapid and widespread Omicron outbreak in China following the adjustment of the COVID-19 policy. Materials and methods: This retrospective observational study involved outpatients visiting the dermatology department at a tertiary referral hospital in Beijing, China between December 2022 and February 2023. Demographics, COVID-19 characteristics, treatment modalities, and dermatosis outcomes were subjected to statistical analysis. Results: The odds ratio (OR) for vitiligo aggravation during COVID-19 was 0.497 [95% confidence interval (CI): 0.254-0.973, p = 0.038] compared to total patients with various dermatoses. Psoriasis patients with a maximum body temperature (Tmax) over 38.6°C during COVID-19 were 2.833 times more likely to experience dermatosis aggravation (OR: 2.833 [1.029-7.803], p = 0.041). Moreover, autoimmune bullous disease (AIBD) patients receiving biologics treatment exhibited a reduced likelihood of aggravation during the COVID-19 outbreak (OR: 0 [0-0.531], p = 0.011). Conclusion: Vitiligo exhibits lower aggravation rates during COVID-19 than other dermatoses. A higher body temperature during COVID-19 infection can increase the risk of psoriasis aggravation. Biologics treatment reduces the risk of AIBD aggravation during the COVID-19 outbreak.
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Introduction: The aging of the skin, which is affected by both external and internal causes, can reflect the external age and the internal health status. While the aging characteristics differ across ethnic groups, the specific changes in skin aging within the Chinese population have been underexplored. Moreover, investigating the similarity of aging skin characteristics between parent-offspring pairs remains uncharted territory. This study aims to fill these gaps by examining the skin aging features of Chinese women and assessing the similarity in aging skin characteristics between mother-daughter pairs. Methods: A total of 40 mother-daughter pairs were recruited and analyzed. The perceived ages of the participants were evaluated, and their aging skin traits were systematically graded. Statistical methods were employed to discern the trends of the aging skin characteristics. By introducing a novel similarity parameter, we compared whether various skin aging characteristics have similar patterns between mothers and daughters. Results: Our findings indicate that age 50 represents a pivotal point in skin aging. Beyond this age, the increase in rhytides and laxity scores accelerated noticeably, whereas the escalation in dyschromia scores became less marked. By introducing similar parameters between mother-daughter pairs and the radar map, we discovered that the skin aging characteristics are remarkably consistent between mother-daughter pairs. Conclusion: Understanding the main aging skin characteristics of different age groups can allow caregivers to devise treatments for preventing skin aging in women of various ages. The mother's skin aging trend is also significant for the daughter's skin aging prevention.
Skin aging, a complex process influenced by both internal and external factors, exhibits distinct patterns across ethnic groups. Despite this, the specific aging characteristics within the Chinese population and the hereditary similarities between parents and offspring have not been thoroughly investigated. To address this gap, our study focused on the skin aging features of Chinese women and explored the resemblance in these features between mother-daughter pairs. Eighty-seven women from the same community, including 40 mother-daughter pairs, participated in our study. We assessed how old each participant appeared to be and methodically evaluated their skin aging signs by a modified scale. With the introduction of a new similarity parameter, we further examined the extent to which skin aging traits showed parallel trends between mothers and their daughters. Our findings pinpoint age 50 as a pivotal moment in the skin aging trajectory, where the increase in wrinkles and skin laxity becomes more pronounced, contrasting with a deceleration in skin discoloration. Remarkably, a consistent pattern of aging characteristics was observed between mother-daughter pairs, suggesting a potential genetic influence. This study not only sheds light on the specific skin aging patterns among Chinese women but also underscores the significance of genetic factors in shaping these patterns. The insights gained pave the way for developing targeted interventions for skin aging prevention and treatment, emphasizing the importance of considering familial aging trends.
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Traumatic brain injury (TBI) is a prevalent form of cranial trauma that results in neural conduction disruptions and damage to synaptic structures and functions. Cannabidiol (CBD), a primary derivative from plant-based cannabinoids, exhibits a range of beneficial effects, including analgesic, sedative, anti-inflammatory, anticonvulsant, anti-anxiety, anti-apoptotic, and neuroprotective properties. Nevertheless, the effects of synaptic reconstruction and the mechanisms underlying these effects remain poorly understood. TBI is characterized by increased levels of tumor necrosis factor-alpha (TNF-α), a cytokine integral for the modulation of glutamate release by astrocytes. In the present study, the potential of CBD in regulating aberrant glutamate signal transmission in astrocytes following brain injury, as well as the underlying mechanisms involved, were investigated using immunofluorescence double staining, enzyme-linked immunosorbent assay (ELISA), western blot analysis, hematoxylin and eosin (H&E) staining, Nissl staining, transmission electron microscopy, and RT-qPCR. In this study, we examined the impact of CBD on neuronal synapses, focusing on the TNF-α-driven purinergic signaling pathway. Specifically, our research revealed that CBD pretreatment effectively reduced the secretion of TNF-α induced by astrocyte activation following TBI. This reduction inhibited the interaction between TNF-α and P2Y1 receptors, leading to a decrease in the release of neurotransmitters, including Ca2+ and glutamate, thereby initiating synaptic remodeling. Our study showed that CBD exhibits significant therapeutic potential for TBI-related synaptic dysfunction, offering valuable insights for future research and more effective TBI treatments. Further exploration of the potential applications of CBD in neuroprotection is required to develop innovative clinical strategies.
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Astrócitos , Lesões Encefálicas Traumáticas , Canabidiol , Transdução de Sinais , Sinapses , Fator de Necrose Tumoral alfa , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Animais , Canabidiol/farmacologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/patologia , Fator de Necrose Tumoral alfa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Masculino , Ratos Sprague-Dawley , Ácido Glutâmico/metabolismo , Fármacos Neuroprotetores/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Ratos , CamundongosRESUMO
Background: Malnutrition is the most common nutritional issue in Alzheimer's disease (AD) patients, but there is still a lack of a comprehensive evaluation of the nutritional status in AD patients. This study aimed to determine the potential association of various nutritional indices with AD at different stages. Methods: Subjects, including individuals with normal cognition (NC) and patients diagnosed with AD, were consecutively enrolled in this cross-sectional study. Demographics, body composition, dietary patterns, nutritional assessment scales and nutrition-related laboratory variables were collected. Binary logistics regression analyses and receiver operating characteristic (ROC) curves were used to indicate the association between nutrition-related variables and AD at different stages. Results: Totals of 266 subjects, including 73 subjects with NC, 72 subjects with mild cognitive impairment due to AD (AD-MCI) and 121 subjects with dementia due to AD (AD-D) were included. There was no significant difference in dietary patterns, including Mediterranean diet and Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) diet between the three groups. Lower BMI value, smaller hip and calf circumferences, lower Mini Nutritional Assessment (MNA) and Geriatric Nutritional Risk Index (GNRI) scores, and lower levels of total protein, albumin, globulin, and apolipoprotein A1 were associated with AD (all p < 0.05). Total protein and albumin levels had the greatest ability to distinguish AD from non-AD (AUC 0.80, 95% CI 0.74-0.84, p < 0.001), increased by combining calf circumference, MNA score and albumin level (AUC 0.83, 95% CI 0.77-0.88, p < 0.001). Albumin level had the greatest ability to distinguish NC from AD-MCI (AUC 0.75, 95% CI 0.67-0.82, p < 0.001), and MNA score greatest ability to distinguish AD-MCI from AD-D (AUC 0.72, 95% CI 0.65-0.78, p < 0.001). Conclusion: Nutritional status of AD patients is significantly compromised compared with normal controls, and tends to be worsened with AD progresses. Early identification and intervention of individuals with nutritional risk or malnutrition may be significantly beneficial for reducing the risk, development, and progression of AD.
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The d-f transition rare earth complexes have recently emerged as a promising candidate for display applications due to the parity-allowed transition, high photoluminescence quantum yield (PLQY), short excited lifetime, and tunable emissions. Besides, inkjet printing has been regarded as an important technique for realizing full-color display. However, inkjet-printed d-f transition rare earth complexes have not been investigated. Herein, for the first time, we explored d-f transition cerium(III) complex 2-Me as the luminescent material by inkjet printing. With 1,2-dichlorobenzene as solvent and polystyrene as an additive, 2-Me film exhibits a similar emission peak and excited-state lifetime with 2-Me powder and a high PLQY of 45%, demonstrating the excellent stability of 2-Me ink. Finally, we suppressed the coffee ring effect and prepared the first inkjet-printed pattern ''HUST'' composed of d-f transition rare earth complex ink with uniform blue fluorescence. Our pioneering work provides a promising alternative for inkjet printing inks.
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AIMS: To investigate the roles of neurotrophic factors on cognition in patients with Alzheimer's disease (AD) carrying Apolipoprotein E (APOE) ε4. METHODS: Totals of 173 patients with AD were divided into APOE ε4 carrier and non-carrier groups, and their demographics, cognition, and neurotrophic factors in cerebrospinal fluid (CSF) were compared. Multiple linear regression analyses were performed to assess correlations among APOE ε4, neurotrophic factors and cognition. Mediation analyses were conducted to assess the sequential associations among APOE ε4, nerve growth factor (NGF), and cognition. RESULTS: Global cognition and multiple domains were impaired in the APOE ε4 carrier group (all p < 0.05). NGF level in the APOE ε4 carrier group was lower than that in the non-carrier group (p = 0.016). NGF level showed significant correlations with both global and multiple domains cognitions. Specifically, NGF mediated the association between APOE ε4 and Animal Fluency Test score (ß, -0.45; 95% CI [-0.96, -0.07]; p < 0.001) and Trail Making Test-A (time) (ß, 0.15; 95% CI [0.01, 0.33]; p < 0.001). CONCLUSION: APOE ε4 is associated with cognitive impairment, and those carrying APOE ε4 have decreased NGF level in CSF. Declined NGF level is correlated with compromised cognition. NGF mediates APOE ε4-associated cognitive impairment.
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Doença de Alzheimer , Apolipoproteína E4 , Disfunção Cognitiva , Fator de Crescimento Neural , Humanos , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Masculino , Feminino , Apolipoproteína E4/genética , Idoso , Fator de Crescimento Neural/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/psicologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Idoso de 80 Anos ou maisRESUMO
Rare earth ions with d-f transitions (Ce3+, Eu2+) have emerged as promising candidates for electroluminescence applications due to their abundant emission spectra, high light conversion efficiency, and excellent stability. However, directly injecting charge into 4f orbitals remains a significant challenge, resulting in unsatisfied external quantum efficiency and high operating voltage in rare earth light-emitting diodes. Herein, we propose a scheme to solve the difficulty by utilizing the energy transfer process. X-ray photoelectron spectroscopy and transient absorption spectra suggest that the Cs3CeI6 luminescence process is primarily driven by the energy transfer from the I2-based self-trapped exciton to the Ce-based Frenkel exciton. Furthermore, energy transfer efficiency is largely improved by enhancing the spectra overlap between the self-trapped exciton emission and the Ce-based Frenkel exciton excitation. When implemented as an active layer in light-emitting diodes, they show the maximum brightness and external quantum efficiency of 1073 cd m-2 and 7.9%, respectively.
RESUMO
BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear. METHODS: Using stepwise calling on next-generation sequencing data from 499 patients with CTEPH referred to 3 centers between October 2006 and December 2021, CHIP mutations were identified. We associated CHIP with all-cause mortality in patients with CTEPH. To provide insights into potential mechanisms, the associations between CHIP and inflammatory markers were also determined. RESULTS: In total, 47 (9.4%) patients with CTEPH carried at least 1 CHIP mutation at a variant allele frequency of ≥2%. The most common mutations were in DNMT3A, TET2, RUNX1, and ASXL1. During follow-up (mean, 55 months), deaths occurred in 22 (46.8%) and 104 (23.0%) patients in the CHIP and non-CHIP groups, respectively (P<0.001, log-rank test). The association of CHIP with mortality remained robust in the fully adjusted model (hazard ratio, 2.190 [95% CI, 1.257-3.816]; P=0.006). Moreover, patients with CHIP mutations showed higher circulating interleukin-1ß and interleukin-6 and lower interleukin-4 and IgG galactosylation levels. CONCLUSIONS: This is the first study to show that CHIP mutations occurred in 9.4% of patients with CTEPH are associated with a severe inflammatory state and confer a poorer prognosis in long-term follow-up.
Assuntos
Doenças Cardiovasculares , Hipertensão Pulmonar , Humanos , Hematopoiese Clonal , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/genética , Hematopoese/genética , Doenças Cardiovasculares/genética , MutaçãoRESUMO
The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.