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Lake Baiyangdian is one of China's largest macrophyte - derived lakes, facing severe challenges related to water quality maintenance and eutrophication prevention. Dissolved organic matter (DOM) was a huge carbon pool and its abundance, property, and transformation played important roles in the biogeochemical cycle and energy flow in lake ecosystems. In this study, Lake Baiyangdian was divided into four distinct areas: Unartificial Area (UA), Village Area (VA), Tourism Area (TA), and Breeding Area (BA). We examined the diversity of DOM properties and sources across these functional areas. Our findings reveal that DOM in this lake is predominantly composed of protein - like substances, as determined by excitation - emission matrix and parallel factor analysis (EEM - PARAFAC). Notably, the exogenous tyrosine-like component C1 showed a stronger presence in VA and BA compared to UA and TA. Ultrahigh - resolution mass spectrometry (FT - ICR MS) unveiled a similar DOM molecular composition pattern across different functional areas due to the high relative abundances of lignan compounds, suggesting that macrophytes significantly influence the material structure of DOM. DOM properties exhibited specific associations with water quality indicators in various functional areas, as indicated by the Mantel test. The connections between DOM properties and NO3N and NH3N were more pronounced in VA and BA than in UA and TA. Our results underscore the viability of using DOM as an indicator for more precise and scientific water quality management.
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Monitoramento Ambiental , Lagos , Lagos/química , China , Monitoramento Ambiental/métodos , Eutrofização , Substâncias Húmicas/análise , Qualidade da Água , Espectrometria de Massas/métodos , Poluentes Químicos da Água/análise , EcossistemaRESUMO
Purple-fleshed sweetpotatoes (PFSPs) are rich in anthocyanins and are one of the health foods of interest. In this study, the effects of steaming on the anthocyanin, starch, soluble sugar, volatile organic compounds (VOCs) and pasting properties of nine PFSPs from China were investigated. The anthocyanin content of raw PFSP ranged from 9 to 185 mg/100 g. The total starch content decreased and soluble sugar content increased in all purple potatoes after steaming. Among the nine PFSPs varieties, Guangshu20 showed the greatest decrease in starch content (30.61%) and the greatest increase in soluble sugar content (31.12%). The pasting properties affected the taste of the PFSPs, with Shuangpihuang having the lowest peak viscosity (720.33 cP) and Guangzishu12 having the highest peak viscosity (2501.67 cP). Correlation studies showed that the anthocyanin content and pasting properties were negatively correlated with most of the sensory indicators, whereas the soluble sugar content of steamed PFSPs was significantly positively correlated with sweetness. A total of 54 VOCs were identified in this study, and aldehydes and terpenoids were the major VOCs in PFSPs. This study provides a theoretical basis for the processing of different PFSP varieties.
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BACKGROUND: Metabolic regulation of various amino acids have been proven to be effective in preventing cardiovascular disease (CVD). The impact of tryptophan, an essential amino acid, on the risk of developing CVD has not been fully elucidated. AIMS: The aim of this meta-analysis was to systematically review evidence of the effects of tryptophan on CVD risk. METHODS: The PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were searched to collect relevant trials from inception to August 2024. The means and hazard ratios (HRs) were extracted and pooled. Subgroup analysis was performed to identify pooled effect estimates, and sensitivity analysis was conducted to assess the robustness of the pooled estimates. RESULTS: Data were collected from 34,370 people under follow-up for CVD events in 13 studies, including cohort studies and case-control studies. They were categorized into three groups on the basis of sample type and indicators: the plasma tryptophan level group, the plasma tryptophan CVD hazard group, and the urinary tryptophan CVD hazard group. The CVD included in this study were coronary artery disease, heart failure, and peripheral artery disease. Twelve studies on plasma tryptophan were meta-analyzed. The plasma tryptophan levels in CVD patients were generally lower than those in individuals without CVD (SMD = -8.57, 95%CI (-15.77, -1.37), P = 0.02). Decreased circulating tryptophan levels are associated with cardiovascular disease risk (HR = 0.85, 95%CI (0.78, 0.92), P < 0.00001). CONCLUSIONS: Decreased circulating tryptophan levels are associated with an increased risk of CVD events. Intervention in circulating tryptophan levels may be indicated to help prevent CVD.
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BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have been shown to improve cardiovascular outcomes by reducing low-density lipoprotein cholesterol (LDL-C). However, sex differences in the efficacy of evolocumab remain unclear. This study aimed to investigate sex differences in the efficacy of evolocumab using real-world data. METHOD: Data were collected from the First Affiliated Hospital of Guangxi Medical University. A total of 416 eligible patients were selected from 1463 patients treated with evolocumab for secondary prevention. Clinical data, including individual characteristics and lipids profiles, were recorded. Propensity score matching (PSM) was used to control for potential confounders, with covariates including age, body mass index, smoking status, and diabetes. All eligible participants were propensity-matched 1:1 for female versus male with a match tolerance of 0.02. The efficacy of evolocumab in females and males was compared by PSM-adjusted analysis. RESULTS: In the PSM analysis, a significant difference was found in the relative percentage reduction of LDL-C between females and males (-42.7% vs. -54.4%, p < 0.001). In addition, the absolute LDL-C reduction was lower in females compared to males (interquartile range: -1.5 [-2.2, -0.8] mmol/L vs. -1.9 [-2.5, -1.0] mmol/L, p = 0.018). The rate of target LDL-C attainment was lower in females than in males after treatment with evolocumab (21.6% vs. 39.8%, p = 0.009). CONCLUSION: These results suggest that males have a better response to evolocumab in term of LDL-C reduction compared to females.
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BACKGROUND: Despite the well-established regulatory role of vitamin D in maintaining bone health, little is known about the shared genetics and causality of the association between serum 25-hydroxyvitamin D (25OHD) and bone mineral density (BMD). METHODS: Leveraging individual-level data from the UK Biobank (UKB) cohort and summary-level data from the genome-wide association studies (GWASs) conducted on European individuals for serum 25OHD (N = 417,580) and estimated heel BMD (eBMD, N = 426,824), we systematically elucidated the shared genetic architecture underlying serum 25OHD and eBMD through a comprehensive genome-wide cross-trait design. RESULTS: Despite a lack of global genetic correlation (rg = -0.001, P = 0.95), a significant local signal was discovered at 5p11-5q11.9. Two-sample Mendelian randomization (MR) indicated no causal association in the overall population (ß = 0.003, 95% CI = -0.04â¼0.03, P = 0.93), while positive causal effects were observed in males (ß = 0.005, 95% CI = 0.00â¼0.01, P = 0.03) and the elderly (ß = 0.009, 95% CI = 0.00â¼0.02, P = 0.01) according to one-sample MR. A total of 49 pleiotropic SNPs, with 4 novel SNPs (rs1077151, rs79873740, rs12150353, and rs4760401), were identified, and a total of 95 gene-tissue pairs exhibited overlap, predominantly enriched in the nervous, digestive, exo-/endocrine and cardiovascular systems. Protein-protein interaction analysis identified RPS9 and RPL7A as hub genes. CONCLUSIONS: This study illuminates the potential health benefits of enhancing serum 25OHD levels to mitigate the risk of osteoporosis among males and the elderly. It also unveils a shared genetic basis between serum 25OHD and eBMD, offering valuable insights into the intricate biological pathways.
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PCOS is one of the most common endocrine disorders among women of reproductive age. While the mechanism involved is not yet fully characterized. Our study aims to examine the pregnancy outcomes of embryo transfers in women with PCOS after pretreatment, and to explore the possible effect of high androgen levels on endometrial receptivity. Retrospective cohort study was conducted to analyze pregnancy outcomes among 2714 infertile women with tubal factor and 452 PCOS women. Endometrium samples were collected from 6 controls and 6 PCOS patients to detect the expression of endometrial receptivity marks. The implantation rate, clinical and ongoing pregnancy rates and live birth rate in women with PCOS followed fresh embryo transfers were obviously decreased even after the pretreatment. Similar pregnancy outcomes were found in frozen-thawed embryo transfer cycles between women with or without PCOS. Strikingly, serum total testosterone (TT) levels on trigger day were significantly higher in PCOS women. Women with high TT levels presented significantly lower clinical and ongoing pregnancy rates, and the expression of insulin-like growth factor binding protein 1 (IGFBP-1), and leukemia inhibitory factor (LIF) in the endometria decreased significantly as well. High doses of testosterone significantly down-regulated the expression of IGFBP-1 and LIF in Ishikawa cells. Although endocrine abnormalities had been improved before the controlled ovarian stimulation (COS) cycle started, higher serum TT levels were detected on the trigger day of the COS cycle in PCOS patients, which may contribute to the decreased fresh embryo implantation by impairing endometrial receptivity.
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Transferência Embrionária , Endométrio , Fator Inibidor de Leucemia , Indução da Ovulação , Síndrome do Ovário Policístico , Testosterona , Humanos , Feminino , Síndrome do Ovário Policístico/metabolismo , Gravidez , Endométrio/metabolismo , Adulto , Indução da Ovulação/métodos , Fator Inibidor de Leucemia/metabolismo , Estudos Retrospectivos , Testosterona/sangue , Taxa de Gravidez , Implantação do Embrião , Infertilidade Feminina/metabolismo , Infertilidade Feminina/sangue , Infertilidade Feminina/terapia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Androgênios/metabolismo , Androgênios/sangue , Resultado da Gravidez , Fertilização in vitro/métodosRESUMO
To understand the structure of the plankton community and the ecological niche characteristics of their dominant species, sampling surveys of plankton were conducted in Baiyangdian Lake in the spring ï¼Marchï¼, summer ï¼Julyï¼, and autumn ï¼Septemberï¼ of 2022. The changes in the plankton community during the three seasons were analyzed by constructing ecological network diagrams, non-metric multidimensional scaling analysis ï¼NMDSï¼, and the ecological niche width. The niche overlap of zooplankton dominant species was evaluated by the improved Levins' formula and Petraitis' index. The interspecific connectivity of dominant species was judged using the chi-square test and interspecies connectivity coefficients. The results showed that the niche width of plankton in the whole area was low. Zooplankton was dominated by rotifers, and phytoplankton was dominated by diatoms, cyanobacteria, and green algae. There were significant seasonal changes in the community structures of plankton. Compared with that in summer and autumn, there were fewer species of plankton in spring and lower interspecies connectivity. The overlap of dominant species of zooplankton was high in summer, and the interspecific competition was intensified, whereas the interspecific overlap of phytoplankton was at a low level in all three seasons. There was a significant positive correlation ï¼W > χ20.05ï¼ between phytoplankton in summer and autumn, and the community structure was stable. The interdomain ecological network of zooplankton and phytoplankton showed a high negative correlation ratio in autumn, especially between copepods and cladoceras of zooplankton and chlorophyta and cyanophyta of phytoplankton. The plankton species in Baiyangdian Lake were abundant, with obvious seasonal differences. The dominant species were mainly a narrow ecological niche. The plankton community was generally in a stable state, and there was a strong predation relationship between copepods and cladoceras and green algae and cyanobacteria.
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Ecossistema , Lagos , Fitoplâncton , Estações do Ano , Zooplâncton , China , Zooplâncton/classificação , Fitoplâncton/classificação , Fitoplâncton/crescimento & desenvolvimento , Animais , Plâncton/classificação , Dinâmica Populacional , Monitoramento Ambiental/métodos , Cianobactérias/crescimento & desenvolvimento , Rotíferos/fisiologia , Rotíferos/crescimento & desenvolvimento , Diatomáceas/crescimento & desenvolvimentoRESUMO
BACKGROUND: Acute myeloid leukaemia (AML) comprises a group of heterogeneous and aggressive haematological malignancies with unsatisfactory prognoses and limited treatment options. Treatments targeting B-cell lymphoma-2 (BCL-2) with venetoclax have been approved for patients with AML, and venetoclax-based drug combinations are becoming the standard of care for older patients unfit for intensive chemotherapy. However, the therapeutic duration of either single or combination strategies is limited, and the development of resistance seems inevitable. Therefore, more effective combination regimens are urgently needed. METHODS: The efficacy of combination therapy with NL101, a SAHA-bendamustine hybrid, and venetoclax was evaluated in preclinical models of AML including established cell lines, primary blasts from patients, and animal models. RNA-sequencing and immunoblotting were used to explore the underlying mechanism. RESULTS: NL101 significantly potentiated the activity of venetoclax in AML cell lines, as evidenced by the enhanced decrease in viability and induction of apoptosis. Mechanistically, the addition of NL101 to venetoclax decreased the stability of the antiapoptotic protein myeloid cell leukaemia-1 (MCL-1) by inhibiting ERK, thereby facilitating the release of BIM and triggering mitochondrial apoptosis. Moreover, the strong synergy between NL101 and venetoclax also relied on the downregulation of c-Myc via PI3K/Akt/GSK3ß signalling. The combination of NL101 and venetoclax synergistically eliminated primary blasts from 10 AML patients and reduced the leukaemia burden in an MV4-11 cell-derived xenograft model. CONCLUSIONS: Our results encourage the pursuit of clinical trials of combined treatment with NL101 and venetoclax and provide a novel venetoclax-incorporating therapeutic strategy for AML.
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Apoptose , Compostos Bicíclicos Heterocíclicos com Pontes , Sinergismo Farmacológico , Leucemia Mieloide Aguda , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-myc , Sulfonamidas , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Linhagem Celular Tumoral , Animais , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Apoptose/efeitos dos fármacos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Transdução de Sinais/efeitos dos fármacos , FemininoRESUMO
Diffuse large B-cell lymphoma (DLBCL) is among the most aggressive hematological malignancies and patients are commonly treated with combinatorial immunochemotherapies such as R-CHOP. Till now, the prognoses are still variable and unsatisfactory, depending on the molecular subtype and the treatment response. Developing effective and tolerable new agents is always urgently needed, and compounds from a natural source have gained increasing attentions. Wogonin is an active flavonoid extracted from the traditional Chinese herbal medicine Scutellaria baicalensis Georgi and has shown extensive antitumor potentials. However, the therapeutic effect of wogonin on DLBCL remains unknown. Here, we found that treatment with wogonin dose- and time-dependently reduced the viability in a panel of established DLBCL cell lines. The cytotoxicity of wogonin was mediated through apoptosis induction, along with the loss of mitochondrial membrane potential and the downregulation of BCL-2, MCL-1, and BCL-xL. In terms of the mechanism, wogonin inhibited the PI3K and MAPK pathways, as evidenced by the clear decline in the phosphorylation of AKT, GSK3ß, S6, ERK, and P38. Furthermore, the combination of wogonin and the BCL-2 inhibitor venetoclax elicited synergistically enhanced killing effect on DLBCL cells regardless of their molecular subtypes. Finally, administration of wogonin significantly impeded the progression of the DLBCL tumor in a xenograft animal model without obvious side effects. Taken together, the present study suggests a promising potential of wogonin in the treatment of DLBCL patients either as monotherapy or an adjuvant for venetoclax-based combinations.
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Exogenous exposure to high concentrations of microplastics (MPs) cause oxidative damage to freshwater food chains (FFCs). Thus, the patterns and mechanisms of oxidative stress responses (OSRs) induced by MPs in FFC organisms were investigated using theoretical simulation methods. Results showed an increasing (reduced) OSR was found in lower trophic levels (higher trophic levels). Besides, polycarbonate (polyvinyl chloride) causes the most (least) significant OSRs in FFC organisms, respectively. The impacts of MP additives were also analyzed using the full factorial experimental design, revealing flame retardants significantly influence oxidative stress variability. A constructive solution of "restriction-control-focus" is proposed for different types of MPs by the coefficient of variation-corrected CRITIC and the nested mean classification method. The mechanism analysis revealed a positive correlation between protein secondary structure orderliness and OSRs. Proteins in organisms that contain a high proportion of hydrophobic non-polar amino acids are more likely to bind to MP and enhance OSRs. This is the first study assessing the OSR patterns and ecological risks of MPs and their additives in FFCs with a proposed priority list, providing theoretical support for risk assessments and management strategies in freshwater environments.
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Abnormal expression of circRNAs has been observed in different types of carcinomas, and they play significant roles in the biology of these cancers. Nevertheless, the clinical relevance and functional mechanisms of the majority of circRNAs implicated in breast cancer progression remain unclear. The primary objective of our investigation is to uncover new circRNAs in breast cancer and elucidate the underlying mechanisms by which they exert their effects. The circRNA expression profile data for breast cancer and RNA-sequencing data were acquired from distinct public databases. Differentially expressed circRNAs and mRNA were identified through fold change filtering. The establishment of the competing endogenous RNAs (ceRNAs) network relied on the interplay between circular RNAs, miRNAs, and mRNAs. The hub genes were identified from the protein-protein interaction (PPI) regulatory network using the CytoHubba plugin in Cytoscape. Moreover, the expression levels and prognostic value of these hub genes in the PPI network were assessed using the GEPIA and Kaplan-Meier plotter databases. Fluorescence in situ hybridization (FISH) was used to identified the expression and intracellular localization of hsa_circ_0059665 by using the tissue microarray. Transwell analysis and CCK-8 analysis were performed to assess the invasion, migration, and proliferation abilities of breast cancer cells. Additionally, we investigated the interactions between hsa_circ_0059665 and miR-602 through various methods, including FISH, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. Rescue experiments were conducted to determine the potential regulatory role of hsa_circ_0059665 in breast cancer progression. A total of 252 differentially expressed circRNAs were identified. Among them, 246 circRNAs were up-regulated, while 6 circRNAs were down-regulated. Based on prediction and screening of circRNA-miRNA and miRNA-mRNA binding sites, we constructed a network consisting of circRNA-miRNA-mRNA interactions. In addition, we constructed a Protein-Protein Interaction (PPI) network and identified six hub genes. Moreover, the expression levels of these six hub genes in breast cancer tissues were found to be significantly lower. Furthermore, the survival analysis results revealed a significant correlation between low expression levels of KIT, FGF2, NTRK2, CAV1, LEP and poorer prognosis in breast cancer patients. The FISH experiment results indicated that hsa_circ_0059665 exhibits significant downregulation in breast cancer, and its decreased expression is linked to poor prognosis in breast cancer patients. Functional in vitro experiments revealed that overexpression of hsa_circ_0059665 can inhibit proliferation, migration and invasion abilities of breast cancer cells. Further molecular mechanism studies showed that hsa_circ_0059665 exerts its anticancer gene role by acting as a molecular sponge for miR-602. In our study, we constructed and analyzed a circRNA-related ceRNA regulatory network and found that hsa_circ_0059665 can act as a sponge for miR-602 and inhibit the proliferation, invasion and migration of breast cancer cells.
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Neoplasias da Mama , Regulação Neoplásica da Expressão Gênica , MicroRNAs , RNA Circular , Humanos , RNA Circular/genética , RNA Circular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Redes Reguladoras de Genes , Perfilação da Expressão Gênica , Mapas de Interação de Proteínas/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Prognóstico , Movimento Celular/genética , Células MCF-7RESUMO
In this study, N, N '-bis {4- [(α-L- rhamnosyloxy) benzyl]} thiourea (PG-1), a phenolic glycoside compound was purified from Moringa seed. The PG-1 has attracted extensive attention due to its anti-cancer, antioxidant, anti-inflammatory and hypoglycemic properties. However, some of its physicochemical properties such as oral bioavailability has not been studied. Herein, a highly purified PG-1 was extracted and incorporated in multiple layered liposomes (PG-1-L) to avoid its burst release and enhance oral bioavailability. After appropriate characterization, it was discovered that the obtained PG-1-L was stable, homogeneous and well dispersed with the average particle size being 89.26 ± 0.23 nm. Importantly, the in vitro release and in vivo oral bioavailability of PG-1-L were significantly improved compared with PG-1. In addition, MTT results showed that compared with the free PG-1, PG-1-L displayed obvious inhibitory effect on the HepG2 cells, while the inhibitory effect on healthy non-malignant 3T6 and LO-2 cells was not significant, indicating that PG-1-L had high safety. In conclusion, PG-1-L can be used as a promising delivery system and an ideal novel approach to improve the oral bioavailability and anticancer activity of PG-1.
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Disponibilidade Biológica , Glicosídeos , Lipossomos , Moringa oleifera , Fenóis , Sementes , Moringa oleifera/química , Sementes/química , Humanos , Glicosídeos/química , Glicosídeos/administração & dosagem , Glicosídeos/farmacologia , Glicosídeos/isolamento & purificação , Animais , Células Hep G2 , Fenóis/administração & dosagem , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacocinética , Tamanho da Partícula , Sistemas de Liberação de Medicamentos/métodos , Camundongos , Masculino , Ratos , Administração Oral , Química Farmacêutica/métodos , Ratos Sprague-DawleyRESUMO
Two researchers independently assessed studies published up to February 5, 2023, across PubMed, Web of Science, Embase, and Cochrane Library, to investigate the associations of sleep traits with cardiometabolic risk factors, as well as with cardiovascular diseases. Fourteen systematic reviews consisting of 23 meta-analyses, and 11 Mendelian randomization (MR) studies were included in this study. Short sleep duration was associated with a higher risk of obesity, type 2 diabetes (T2D), hypertension, stroke, and coronary heart disease (CHD) in observational studies, while a causal role was only demonstrated in obesity, hypertension, and CHD by MR. Similarly, long sleep duration showed connections with a higher risk of obesity, T2D, hypertension, stroke, and CHD in observational studies, none was supported by MR analysis. Both observational and MR studies indicated heightened risks of hypertension, stroke, and CHD in relation to insomnia. Napping was linked to elevated risks of T2D and CHD in observational studies, with MR analysis confirming a causal role in T2D. Additionally, snoring was correlated with increased risks of stroke and CHD in both observational and MR studies. This work consolidates existing evidence on a causal relationship between sleep characteristics and cardiometabolic risk factors, as well as cardiovascular diseases.
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Fatores de Risco Cardiometabólico , Doenças Cardiovasculares , Análise da Randomização Mendeliana , Sono , Humanos , Sono/fisiologia , Diabetes Mellitus Tipo 2/genética , Estudos Observacionais como Assunto , Obesidade/complicações , Obesidade/genética , Hipertensão/genética , Acidente Vascular Cerebral , Fatores de RiscoRESUMO
Suppressor of Mek1 (Smek1) is a regulatory subunit of protein phosphatase 4. Genome-wide association studies have shown the protective effect of SMEK1 in Alzheimer's disease (AD). However, the physiological and pathological roles of Smek1 in AD and other tauopathies are largely unclear. Here, the role of Smek1 in preventing neurodegeneration is investigated in tauopathy. Smek1 is downregulated in the aged human brain. Through single-cell sequencing, a novel neuronal cluster is identified that possesses neurodegenerative characteristics in Smek1-/- mice. Smek1 deficiency caused markedly more severe motor and cognitive impairments in mice, as well as neuronal loss, gliosis, and tau hyperphosphorylation at major glycogen synthase kinase 3ß (Gsk3ß) sites. Protein-protein interaction analysis revealed that the Ran-binding domain (RanBD) in the N-terminus of Smek1 facilitated binding with kinesin family member 2A (Kif2a). Depletion of Smek1 resulted in cytoplasmic aggregation of Kif2a, axon outgrowth defects, and impaired mitochondrial axonal trafficking. Downregulation of Kif2a markedly attenuated tau hyperphosphorylation and axon outgrowth defects in shSmek1 cells. For the first time, this study demonstrates that Smek1 deficiency progressively induces neurodegeneration by exacerbating tau pathology and mitochondrial dysfunction in an age-dependent manner.
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Modelos Animais de Doenças , Microtúbulos , Tauopatias , Animais , Camundongos , Tauopatias/metabolismo , Tauopatias/genética , Tauopatias/patologia , Humanos , Microtúbulos/metabolismo , Microtúbulos/genética , Proteínas tau/metabolismo , Proteínas tau/genética , Camundongos Knockout , Cinesinas/genética , Cinesinas/metabolismo , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Encéfalo/metabolismo , Encéfalo/patologiaRESUMO
BACKGROUND: Intestinal obstruction represents a severe intestinal disease associated with higher mortality rates. However, the determinants of mortality in patients with intestinal obstruction remain inadequately understood. This study sought to elucidate the potential risk factors associated with mortality in the context of intestinal obstruction during the COVID-19 pandemic. METHODS: A retrospective analysis was performed on a cohort of 227 patients diagnosed with intestinal obstruction at the First Hospital of Hebei Medical University, spanning the period from September 7, 2022, to January 7, 2023. The primary endpoint of the study was mortality within four weeks following discharge. Univariate and multivariable logistic regression models were utilized to evaluate the risk factors associated with mortality outcomes. RESULTS: A cohort of 227 patients diagnosed with intestinal obstruction (median age, 59.02 years [IQR, 48.95-70.85 years]) was included in our study. Malignant bowel obstruction (MBO) and COVID-19 were identified as independent risk factors for mortality among these patients. Notably, the mortality rate increased significantly to 38.46% when MBO was concomitant with COVID-19. Furthermore, postoperative pulmonary complications (PPC) (OR, 54.21 [death]; 95% CI, 3.17-926.31), gastric cancer (OR, 9.71 [death]; 95% CI, 1.38-68.18), VTE (Caprini Score ≥ 5) (OR, 7.64 [death]; 95% CI, 1.37-42.51), and COVID-19 (OR, 5.72 [death]; 95% CI, 1.01-32.29) were all determined to be independent risk factors for postoperative mortality. Additionally, gastric cancer could have emerged as one of the most severe risk factors for mortality in individuals with intestinal obstruction within the cohort of cancer patients, of which gastric cancer exhibited higher mortality rates compared to individuals with other forms of cancer. CONCLUSION: The study identifies MBO, gastric cancer, COVID-19, PPC, and VTE as potential risk factors for mortality in cases of intestinal obstruction. These findings highlight the necessity for continuous monitoring of indicators related to these mortality risk factors and their associated complications, thereby offering valuable insights for the management and treatment of intestinal obstruction.
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COVID-19 , Obstrução Intestinal , Humanos , Obstrução Intestinal/mortalidade , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Feminino , COVID-19/complicações , COVID-19/mortalidade , Idoso , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/epidemiologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/complicaçõesRESUMO
It has been demonstrated that an enriched environment (EE) treatment can alter neuroplasticity in neurodegenerative diseases. However, the role of EE treatment in ischemic stroke remains unclear. Previous findings have revealed that EE treatment can promote cerebral activin-receptor-like-kinase-5 (ALK5) expression after cerebral ischemia/reperfusion (I/R) injury. ALK5 has been identified as a potential mediator of neuroplasticity through its modulation of Smad2/3 and Gadd45ß. Therefore, the aim of this study was to investigate whether EE treatment could promote neurofunctional recovery by regulating the ALK5/Smad2/3/Gadd45ß pathway. The study utilized the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). The ALK5/Smad2/3/Gadd45ß signaling pathway changes were evaluated using western blotting (WB). Brain injury was assessed by infarct volume and neurobehavioral scores. The effect of EE treatment on neurogenesis was evaluated using Doublecortin (DCX) and Nestin, axonal plasticity with biotinylated dextran amine (BDA) nerve tracing, and dendritic plasticity was assessed using Golgi-Cox staining. EE treatment has been demonstrated to modulate the Smad2/3/Gadd45ß pathway by regulating the expression of ALK5. The protective effects of EE treatment on brain infarct volume, neurological function, newborn neurons, dendritic and axonal plasticity following cerebral I/R injury were counteracted by ALK5 silencing. EE treatment can enhance neurofunctional recovery after cerebral I/R injury, which is achieved by regulating the ALK5/Smad2/3/Gadd45ß signaling pathway to promote neuroplasticity.
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Ratos Sprague-Dawley , Receptor do Fator de Crescimento Transformador beta Tipo I , Traumatismo por Reperfusão , Transdução de Sinais , Proteína Smad2 , Animais , Masculino , Transdução de Sinais/fisiologia , Proteína Smad2/metabolismo , Ratos , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Traumatismo por Reperfusão/metabolismo , Recuperação de Função Fisiológica/fisiologia , Proteína Duplacortina , Proteína Smad3/metabolismo , Isquemia Encefálica/metabolismo , Meio Ambiente , Infarto da Artéria Cerebral Média/metabolismo , Plasticidade Neuronal/fisiologia , Proteínas GADD45 , Antígenos de DiferenciaçãoRESUMO
Surface Plasmon Resonance (SPR) technology, as a powerful analytical tool, plays a crucial role in the preparation, performance evaluation, and biomedical applications of nanoparticles due to its real-time, label-free, and highly sensitive detection capabilities. In the nanoparticle preparation process, SPR technology can monitor synthesis reactions and surface modifications in real-time, optimizing preparation techniques and conditions. SPR enables precise measurement of interactions between nanoparticles and biomolecules, including binding affinities and kinetic parameters, thereby assessing nanoparticle performance. In biomedical applications, SPR technology is extensively used in the study of drug delivery systems, biomarker detection for disease diagnosis, and nanoparticle-biomolecule interactions. This paper reviews the latest advancements in SPR technology for nanoparticle preparation, performance evaluation, and biomedical applications, discussing its advantages and challenges in biomedical applications, and forecasting future development directions.
Assuntos
Nanopartículas , Ressonância de Plasmônio de Superfície , Ressonância de Plasmônio de Superfície/métodos , Nanopartículas/química , Humanos , Sistemas de Liberação de Medicamentos/métodosRESUMO
Bio-oil derived from biomass fast pyrolysis can be upgraded to gasoline and diesel alternatives by catalytic hydrodeoxygenation (HDO). Here, the novel nitrogen-doped carbon-alumina hybrid supported cobalt (Co/NCAn, n = 1, 2.5, 5) catalyst is established by a coagulation bath technique. The optimized Co/NCA2.5 catalyst presented 100 % conversion of guaiacol, high selectivity to cyclohexane (93.6 %), and extremely high deoxygenation degree (97.3 %), respectively. Therein, the formation of cyclohexanol was facilitated by stronger binding energy and greater charge transfer between Co and NC which was unraveled by density functional theory calculations. In addition, the appropriate amount of Lewis acid sites enhanced the cleavage of the C-O bond in cyclohexanol, finally resulting in a remarkable selectivity for cyclohexane. Finally, the Co/NCA2.5 catalyst also exhibited excellent selectivity (93.1 %) for high heating value hydrocarbon fuel in crude bio-oil HDO. This work provides a theoretical basis on N dopants collaborating alumina hybrid catalysts for efficient HDO reaction.