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BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults. METHODS: The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for. RESULTS: The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (ß = - 0.036 and ß = 0.028, respectively, P < 0.05). However, higher baseline HDL-C levels did not significantly predict cognitive performance or depression 4 years later (ß = - 0.008 and ß = 0.023, respectively, P > 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (ß = - 0.026 and ß = - 0.053, respectively, P < 0.05). CONCLUSIONS: Cognitive impairment and depression are associated with higher HDL-C levels, whereas higher HDL-C levels do not appear to protect against cognitive decline or depressive symptoms. These findings underscore the importance of preserving cognitive and mental health, which may lower the likelihood of cardiovascular disease and dementia. Future studies should validate these findings and develop targeted interventions tailored to specific populations.
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HDL-Colesterol , Disfunção Cognitiva , Depressão , Humanos , HDL-Colesterol/sangue , Disfunção Cognitiva/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Depressão/sangue , Depressão/epidemiologia , Idoso , China/epidemiologia , Estudos Longitudinais , Fatores de Risco , Cognição , População do Leste AsiáticoRESUMO
In the context of the rapid development of the Internet of Vehicles, virtual reality, automatic driving and the industrial Internet, the terminal devices in the network show explosive growth. As a result, more and more information is generated from the edge of the network, which makes the data throughput increase dramatically in the mobile communication network. As the key technology of the fifth-generation mobile communication network, mobile edge caching technology which caches popular data to the edge server deployed at the edge of the network avoids the data transmission delay of the backhaul link and the occurrence of network congestion. With the growing scale of the network, distributing hot data from cloud servers to edge servers will generate huge energy consumption. To realize the green and sustainable development of the communication industry and reduce the energy consumption of distribution of data that needs to be cached in edge servers, we make the first attempt to propose and solve the problem of edge caching data distribution with minimum energy consumption (ECDDMEC) in this paper. First, we model and formulate the problem as a constrained optimization problem and then prove its NP-hardness. Subsequently, we design a greedy algorithm with computational complexity of O(n2) to solve the problem approximately. Experimental results show that compared with the distribution strategy of each edge server directly requesting data from the cloud server, the strategy obtained by the algorithm can significantly reduce the energy consumption of data distribution.
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As multiprocessor systems continue to grow in processor scale, the incidence of faults also increases. As a result, fault diagnosis is becoming a key mechanism for maintaining the normal operation of multiprocessor systems. To explore more effective diagnostic methods, Somani et al. introduced a generalized pessimistic diagnostic strategy, named t/k-diagnosis, in which all faulty nodes are isolated in a set of nodes and at most k fault-free nodes are misdiagnosed, provided that the quantity of faults is limited by t. By imposing certain conditions or restrictions, the t/k-diagnosability of some regular networks under the Preparata, Metze, and Chien (PMC) model has been determined. However, the t/k-diagnosability of many networks under the comparison model remains unidentified. In this paper, we provide new insights into the study of t/k-diagnosability under the comparison model. After introducing some new notions, such as the 0-test unit, 0-test set and 0-test subgraph, under the comparison model, we study the relationship in a system G between the 0-test subgraphs and the components of G-F, where F is the set of faulty nodes, and we obtain some important correlation properties. Based on these results, we study t/k-diagnosability under the comparison model. As a result, the t/k-diagnosability of some regular interconnection networks can be efficiently determined.
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Optimizing photosynthesis is imperative for providing energy and organics for all life on the earth. Here, carbon dots doped with pyridinic nitrogen (named lev-CDs) are synthesized by the one-pot hydrothermal method, and the structure-function relationship between functional groups on lev-CDs and photosynthesis of Chlorella pyrenoidosa (C. pyrenoidosa) is proposed. Pyridinic nitrogen plays a key role in the positive effect on photosynthesis caused by lev-CDs. In detail, lev-CDs act as electron donors to supply photo-induced electrons to P680+ and QA+ , causing electron transfer from lev-CDs to the photosynthetic electron transport chain in the photosystems. In return, the recombination efficiency of electron-hole pairs on lev-CDs decreases. As a result, the electron transfer rate in the electron transport chain, the activity of photosystem II, and the Calvin cycle are enhanced. Moreover, the electron transfer rate between C. pyrenoidosa and external circumstances enhanced by lev-CDs is about 50%, and electrons exported from C. pyrenoidosa can be used to reduce iron(III). This study is of great significance for engineering nanomaterials to improve photosynthesis.
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Chlorella , Pontos Quânticos , Transporte de Elétrons , Elétrons , Carbono/farmacologia , Nitrogênio , Compostos Férricos/farmacologia , FotossínteseRESUMO
Background: High-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase (CK)-MB are the most commonly used biomarkers for the diagnosis and prognosis of acute myocardial infarction (AMI). Chronic kidney disease (CKD) often leads to elevated hs-cTnT levels in non-AMI patients. However, studies comparing the prognostic value of both hs-cTnT and CK-MB in patients with AMI and CKD are lacking.Methods: We conducted a retrospective study on AMI patients diagnosed between January 2015 and October 2020. Patients were categorized based on renal function as normal or CKD. Peak hs-cTnT and CK-MB levels during hospitalization were collected, and their diagnostic value was evaluated using receiver operating characteristic (ROC) curves. The impact on in-hospital mortality was analyzed using multivariate logistic regression. The relationship between the hs-cTnT/CK-MB ratio and in-hospital death was examined using a restricted cubic spline (RCS) curve.Results: The study included 5022 AMI patients, of whom 797 (15.9%) had CKD. The AUCs of Hs-cTnT and CK-MB were higher in the CKD group [0.842 (95% CI: 0.789-0.894) and 0.821 (95% CI: 0.760-0.882)] than in the normal renal function group [0.695 (95% CI: 0.604-0.790) and 0.708 (95% CI: 0.624-0.793)]. After full adjustment for all risk factors, hs-cTnT (OR, 2.82; 95% CI, 1.03-9.86; p = 0.038) and CK-MB (OR, 4.91; 95% CI, 1.54-14.68; p = 0.007) above the cutoff values were independent predictors of in-hospital mortality in patients with CKD. However, in patients with normal renal function, only CK-MB above the cutoff (OR, 2.45; 95% CI, 1.02-8.24; p = 0.046) was a predictor of in-hospital mortality, whereas hs-cTnT was not. There was an inverted V-shaped relationship between the hs-cTnT/CK-MB ratio and in-hospital mortality, with an inflection point of 19.61. The ratio within the second quartile (9.63-19.6) was an independent predictor of in-hospital mortality in patients with CKD (OR 5.3, 95% CI 1.66-16.86, p = 0.005).Conclusions: Hs-cTnT independently predicted in-hospital mortality in AMI patients with CKD, whereas its predictive value was not observed in patients with normal renal function. CK-MB was an independent predictor of in-hospital mortality regardless of renal function. Moreover, the hs-cTnT/CK-MB ratio may aid in risk stratification of AMI patients with CKD.
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Infarto do Miocárdio , Insuficiência Renal Crônica , Humanos , Troponina T , Creatinina , Prognóstico , Estudos Retrospectivos , Mortalidade Hospitalar , Infarto do Miocárdio/diagnóstico , BiomarcadoresRESUMO
By combining surface molecular imprinting technology with cysteine-modified ZnS quantum dots, an elegant, molecularly imprinted cysteine-modified Mn2+: ZnS QDs (MIP@ZnS QDs) based fluorescence sensor was successfully developed. The constructed fluorescence sensor is based on a molecularly imprinted polymer (MIP) coated on the surface cysteine-modified ZnS quantum dots and used for rapid fluorescence detection of dopamine hydrochloride. The MIP@ZnS quantum dots possess the advantages of rapid response, high sensitivity, and selectivity for the detection of dopamine hydrochloride molecules. Experimental results show that the adsorption equilibrium time of MIP@ZnS QDs for dopamine hydrochloride molecules is 12 min, and it can selectively capture and bind dopamine in the sample with an imprinting factor of 29.5. The fluorescence quenching of MIP@ZnS QDs has a good linear (R2 = 0.9936) with the concentration of dopamine hydrochloride ranged from 0.01 to 1.0 µM, and the limit of detection is 3.6 nM. In addition, The MIP@ZnS QDs demonstrate good recyclability and stability and are successfully employed for detection of dopamine hydrochloride in urine samples with recoveries was 95.2% to 103.8%. The proposed MIP@ZnS QDs based fluorescent sensor provides a promising approach for food safety detection and drug analysis.
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Impressão Molecular , Pontos Quânticos , Dopamina , Cisteína , Polímeros , Compostos de Zinco , Polímeros Molecularmente Impressos , Impressão Molecular/métodos , Limite de DetecçãoRESUMO
Background: Current guidelines recommend the use of potent antiplatelet agents in patients undergoing percutaneous coronary intervention (PCI) following an acute coronary syndrome (ACS). However, data about optimal platelet inhibition in severe renal insufficiency patients are scarce. The purpose of this study is to determine if ticagrelor is more effective than clopidogrel in patients with ACS and severe renal insufficiency treated with PCI. Methods: We retrospectively enrolled patients with ACS and severe renal insufficiency (eGFR ≤ 30 ml/min·1.73 m2 or dialysis) who underwent PCI at our hospital between January 2015 and March 2020. We used the adjusted Cox proportional hazards models to analyze the 1-year outcome endpoints, including the primary endpoint (the composite of cardiovascular death, recurrence of MI, or nonfatal ischemic stroke), death from any cause, and bleeding events (Bleeding Academic Research Consortium, BARC criteria). Results: A total of 276 patients with ACS and severe renal insufficiency who were treated with PCI with ticagrelor (n = 108) or clopidogrel (n = 168) were included in the study. After adjustment, there was no statistical difference in risk of the primary endpoint (HR, 0.78; 95% CI, 0.46-1.33; P=0.367) and death from any cause (HR, 0.86; 95% CI, 0.38-1.89; P=0.708) in the ticagrelor group against the clopidogrel group. However, the risk of total bleeding was significantly higher in the ticagrelor group (HR, 3.01; 95% CI, 1.81-5.62; P=0.01). Subgroup analysis according to the confounders did not identify any significant subgroup heterogeneity. Conclusion: Ticagrelor did not improve the major adverse cardiovascular events and all-cause mortality when compared to clopidogrel, but significantly increased the risk of bleeding in Chinese patients with ACS and severe renal insufficiency undergoing PCI.
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Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Insuficiência Renal , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Clopidogrel/uso terapêutico , Hemorragia/induzido quimicamente , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Insuficiência Renal/complicações , Estudos Retrospectivos , Ticagrelor/uso terapêutico , Resultado do TratamentoRESUMO
Glutamate decarboxylase (GAD, EC 4.1.1.15) is an important enzyme in gamma-aminobutyric acid biosynthesis and DL-glutamic acid resolution. In this study, the Enterococcus faecium-derived GAD was successfully immobilized by regenerated chitin (RC) via specific adsorption of cellulose-binding domain (CBD). The optimal binding buffer was 20 mmol/L phosphate buffer saline (pH 8.0), and the RC binding capacity was 1.77 ± 0.11 mgcbd-gad/grc under this condition. The ratio of wet RC and crude enzyme solution used for immobilization was recommended to 3:50 (g/mL). To evaluate the effect of RC immobilization on GAD, properties of the immobilize GAD (RC-CBD-GAD) were investigated. Results indicated RC-CBD-GAD was relatively stable at pH 4.4-5.6 and temperature - 20-40 °C, and the optimal reaction pH value and temperature were pH 4.8 and 50 °C, respectively. When it was reacted with 5 mmol/L of follow chemical reagents respectively, the activity of RC-CBD-GAD was hardly affected by EDTA, KCl, and NaCl, and significantly inactivated by AgNO3, MnSO4, MgSO4, CuSO4, ZnSO4, FeCl2, FeCl3, AlCl3, CaCl2, and Pb(CH3COO)2. The apparent Km and Vmax were 28.35 mmol/L and 147.06 µmol/(gRC-CBD-GAD·min), respectively. The optimum time for a batch of catalytic reaction without exogenous pH control was 2 h. Under this reaction time, RC-CBD-GAD had a good reusability with a half-life of 23 cycles, indicating that it was very attractive for GABA industry. As a novel, efficient, and green CBD binding carrier, RC provides an alternative way to protein immobilization.
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Enterococcus faecium/enzimologia , Enzimas Imobilizadas/química , Glutamato Descarboxilase/química , Ácido gama-Aminobutírico/biossíntese , Adsorção , Quitina/química , Ácido Glutâmico/química , Ácido gama-Aminobutírico/químicaRESUMO
BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a potential therapeutic target in acute coronary syndromes. Although recent evidence does not support the routine use of manual thrombus aspiration (TA) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), the use of TA is associated with a significant improvement in myocardial reperfusion, especially in patients with high thrombus burden (HTB). We hypothesized that TA would reduce the serum Lp-PLA2 levels in STEMI patients undergoing PPCI with HTB. METHODS AND RESULTS: Our study cohort included 320 consecutive STEMI patients undergoing PPCI with HTB who were randomly assigned to receive either TA before PPCI (TA group, n = 160) or PPCI alone (standard PPCI group, n = 160). The baseline characteristics of study participants were well-matched. After 30 ± 2 days, serum Lp-PLA2 levels decreased by 53.9% in the TA group (152.9 ± 58.1 ng/mL) and decreased by 31.2% in the standard PPCI group (84.2 ± 86.6 ng/mL, p < 0.001). The TA group had a significantly lower prevalence of balloon predilatation, number of stents used, total stent length and corrected thrombolysis in myocardial infarction frame count, and a higher percentage of myocardial blush grade ≥ 2 compared with the standard PPCI group (all p < 0.001). No significant difference between the groups was observed in 30 ± 2 days for major adverse cardiovascular and cerebrovascular events (p = 0.702). CONCLUSIONS: After 30 ± 2 days of treatment, TA may significantly reduce serum levels of Lp-PLA2 in STEMI patients undergoing PPCI with HTB.
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The emergence of nanomotor provides an innovative concept for tumor treatment strategies. Conventional chemotherapeutic agents for tumors exit various therapeutic constraints due to the unique microenvironment of the tumor itself. Calcium overload, the aberrant accumulation of free calcium ions in the cytoplasm, is a well-recognized contributor to damage and even cell death in numerous cell types. Such undesired destructive processes can be a novel means applicable to cancer ion interference therapy. Herein, the chemotherapeutic drug doxorubicin (DOX) and calcium peroxide as the driving force into nanomotors through a facile and understandable experimental scheme are successfully assembled. The modification of nucleic acid aptamer and NIR-II fluorescent molecules on its surface simultaneously strengthens both the active targeting and imaging capability of tumor loci. Therefore, by a comprehensive assessment of nanomotors both in vitro and in vivo experiments, CaO2/DOX@HPS-IR-1061-AS1411 demonstrates superior killing effects on tumor cells, and the intracellular reactive oxygen species produced by nanomotors is verified by molecular biology experiments to induce apoptosis of tumor cells and further achieve tumor therapeutic effects.
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Doxorrubicina , Neoplasias , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Humanos , Animais , Linhagem Celular Tumoral , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Espécies Reativas de Oxigênio/metabolismo , Peróxidos/química , Peróxidos/farmacologia , Apoptose/efeitos dos fármacos , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/farmacologia , Nanopartículas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Camundongos Nus , Camundongos Endogâmicos BALB CRESUMO
A photocatalytic radical cascade with an unusual endo-trig cyclization was developed, which enables the efficient assembly of divergent tricyclic diterpenoid frameworks. The first total synthesis of abietane 10-epi-epoxyhinoliol was thus achieved in six steps by a subsequent reductive coupling of i-PrBr under photoredox/nickel dual catalysis. Inhibitory tests of chiral 10-epi-epoxyhinoliol and its analogues in 4T1 cancer cells demonstrated the critical role of the C12 hydroxyl group, leading to a discovery of the simplified analogue with better activity.
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Antineoplásicos , Ciclização , Catálise , Estrutura Molecular , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Abietanos/química , Abietanos/farmacologia , Abietanos/síntese química , Humanos , Estereoisomerismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacosRESUMO
AIMS: To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction. METHODS: In vitro: the mobility of the rat bone mesenchymal stem cells (BMSCs) treated with SLPI was evaluated by scratch assay. Then the expression levels of osteogenic differentiation-related genes were analyzed by real-time quantitative PCR (qPCR) to determine the osteogenic effect of SLPI on BMSCs. In vivo: a rat model of ACL reconstruction was used to verify the effect of SLPI on tendon-to-bone healing. All the animals of the SLPI group and the negative control (NC) group were euthanized for histological evaluation, micro-CT scanning, and biomechanical testing. RESULTS: SLPI improved the migration ability of BMSCs and upregulated the expression of genes related to osteogenic differentiation of BMSCs in vitro. In vivo, the SLPI group had higher histological scores at the tendon-bone interface by histological evaluation. Micro-CT showed more new bone formation and bone ingrowth around the grafted tendon in the SLPI group. Evaluation of the healing strength of the tendon-bone connection showed that the SLPI group had a higher maximum failure force and stiffness. CONCLUSION: SLPI can effectively promote early tendon-to-bone healing after ACL reconstruction via enhancing the migration and osteogenic differentiation of BMSCs. Cite this article: Bone Joint Res 2022;11(7):503-512.
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Intervertebral disc degeneration (IDD) is the main cause of low back pain. An increasing number of studies have suggested that inflammatory response or the senescence of nucleus pulposus (NP) cells is strongly associated with the progress of IDD. Eupatilin, the main flavonoid extracted from Artemisia, was reported to be associated with the inhibition of the intracellular inflammatory response and the senescence of cells. However, the relationship between eupatilin and IDD is still unknown. In this study, we explored the role of eupatilin in tumor necrosis factor-α (TNF-α)-induced activation of inflammatory signaling pathways and NP cell senescence, in the anabolism and catabolism of NP cell extracellular matrix (ECM) and in the effect of the puncture-induced model of caudal IDD in the rat. In vitro, eupatilin significantly inhibited TNF-α-induced ECM degradation, downregulated the expression of related markers of NP cells (MMP3, MMP9, and MMP13), and upregulated the expression of SOX9 and COL2A1. Furthermore, eupatilin reduced TNF-α-induced cell senescence by inhibiting the expression of the senescence of NP cell-related markers (p21 and p53). Mechanistically, ECM degradation and cell senescence were reduced by eupatilin, which inhibited the activation of MAPK/NF-κB signaling pathways. Consistent with the in vitro data, eupatilin administration ameliorated the puncture-induced model of caudal IDD in the rat. In conclusion, eupatilin can inhibit the inflammatory response and the senescence of NP cells, which may be a novel treatment strategy for IDD.
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Carbon dots (CDs) with exciting photoluminescence characteristics, mild toxicity, and good biocompatibility are the research hotspots in biomedical application. Here, a compact antibacterial activity of CDs from levofloxacin hydrochloride is reported. The obtained CDs with an average size of 1.27 nm have fascinating antibacterial properties against both gram-positive and negative bacteria, with minimum inhibitory concentrations (MICs) of 64, 128, 64, and 128 µg/mL for Escherichia coli (E. coli),Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis). The antibacterial processes of CDs from extracellular to intracellular were demonstrated, including physical/chemical binding to membrane, wrapping on the surface, destruction of the cell membrane, and promoting reactive oxygen species (ROS) production into the cell without additional light or oxidant. Surprisingly, CDs exert moderate cytotoxicity on mammalian cells at the equivalent bactericidal concentration, in which the cell viability is more than 80% at 100 µg/mL of CDs. The investigation of antibacterial CDs may provide a useful avenue for further exploiting CD-based nano-bactericides in biomedical applications.
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Carbono , Staphylococcus aureus , Animais , Antibacterianos/farmacologia , Bactérias , Carbono/farmacologia , Escherichia coli , Mamíferos , Pseudomonas aeruginosaRESUMO
BACKGROUND: Lumbar disc herniation (LDH) is an important factor of causing leg pain and numbness. As a secondary discipline of Traditional Chinese Medicine, tuina is widely used for the treatment of LDH in China even in other nations while its clinical value is not acknowledged universally. So, we focus on this article aims to evaluate its efficacy and safety of LDH. METHODS: Electronic databases involving Cochrane Library, PubMed, Web of Science, EMBASE, China Science and Technology Journal, China National Knowledge Infrastructure, Wanfang and Chinese Biomedical Literature Database will be pertained with appropriate search strategy. And RevMan V.5.3.5 software will be conducted as the assessment tool for bias risk, data synthesis, subgroup analysis as well as meta-analyses. RESULTS: This systematic review will provide a high-quality synthesis of current evidence of tuina for LDH. CONCLUSION: This protocol will determine whether Tuina is an effective and safe treatment method for LDH.